Articles
Safety, efficacy, and tolerability of efgartigimod in patients
Lancet Neurol 2021; 20: 526–36
See Comment page 499
*Study group members are in the
appendix (pp 15–23)
Department of Neurology,
The University of
North Carolina at Chapel Hill,
Chapel Hill, NC, USA
(Prof J F Howard Jr MD); Ellen &
Martin Prosserman Centre for
Neuromuscular Diseases,
University Health Network,
University of Toronto, Toronto,
ON, Canada (V Bril MD);
Department of Neurology,
University of South Florida
Morsani College of Medicine,
Tampa, FL, USA (Prof T Vu MD);
Penn Neuroscience
Center-Neurology, Hospital of
the University of Pennsylvania,
Philadelphia, PA, USA
(C Karam MD); Neurology Clinic,
Clinical Center of Serbia,
Faculty of Medicine, University
of Belgrade, Belgrade, Serbia
(S Peric MD); Department of
Neurology and
Neurorehabilitation,
New Hospitals, Tbilisi, Georgia
(T Margania MD); Department
of Neurology, School of
Medicine, International
University of Health and
Welfare, Narita, Japan
(Prof H Murai MD); Department
and Clinic of Neurology,
Wroclaw Medical University,
Wroclaw, Poland
(M Bilinska MD); Sarajishvili
Institute of Neurology and
Neurosurgery, Tbilisi, Georgia
(R Shakarishvili MD);
Department of Hematology
and Bone Marrow
Transplantation, Medical
University of Silesia, Katowice,
Poland (M Smilowski MD);
argenx, Ghent, Belgium
(A Guglietta MD, P Ulrichts PhD,
T Vangeneugden PhD);
Department of Neurology,
Hanamaki General Hospital,
Hanamaki, Japan
(K Utsugisawa MD); Department
of Neurology, Leiden
526
with generalised myasthenia gravis (ADAPT):
a multicentre, randomised, placebo-controlled, phase 3 trial
James F Howard Jr, Vera Bril, Tuan Vu, Chafic Karam, Stojan Peric, Temur Margania, Hiroyuki Murai, Malgorzata Bilinska, Roman Shakarishvili,
Marek Smilowski, Antonio Guglietta, Peter Ulrichts, Tony Vangeneugden, Kimiaki Utsugisawa, Jan Verschuuren, Renato Mantegazza,
and the ADAPT Investigator Study Group*
Summary
Background There is an unmet need for treatment options for generalised myasthenia gravis that are effective,
targeted, well tolerated, and can be used in a broad population of patients. We aimed to assess the safety and efficacy
of efgartigimod (ARGX-113), a human IgG1 antibody Fc fragment engineered to reduce pathogenic IgG autoantibody
levels, in patients with generalised myasthenia gravis.
Methods ADAPT was a randomised, double-blind, placebo-controlled, phase 3 trial done at 56 neuromuscular
academic and community centres in 15 countries in North America, Europe, and Japan. Patients aged at least 18 years
with generalised myasthenia gravis were eligible to participate in the study, regardless of anti-acetylcholine receptor
antibody status, if they had a Myasthenia Gravis Activities of Daily Living (MG-ADL) score of at least 5
(>50% non-ocular), and were on a stable dose of at least one treatment for generalised myasthenia gravis. Patients
were randomly assigned by interactive response technology (1:1) to efgartigimod (10 mg/kg) or matching placebo,
administered as four infusions per cycle (one infusion per week), repeated as needed depending on clinical response
no sooner than 8 weeks after initiation of the previous cycle. Patients, investigators, and clinical site staff were all
masked to treatment allocation. The primary endpoint was proportion of acetylcholine receptor antibody-positive
patients who were MG-ADL responders (≥2-point MG-ADL improvement sustained for ≥4 weeks) in the first
treatment cycle. The primary analysis was done in the modified intention-to-treat population of all acetylcholine
receptor antibody-positive patients who had a valid baseline MG-ADL assessment and at least one post-baseline
MG-ADL assessment. The safety analysis included all randomly assigned patients who received at least one dose or
part dose of efgartigimod or placebo. This trial is registered at ClinicalTrials.gov (NCT03669588); an open-label
extension is ongoing (ADAPT+, NCT03770403).
Findings Between Sept 5, 2018, and Nov 26, 2019, 167 patients (84 in the efgartigimod group and 83 in the placebo
group) were enrolled, randomly assigned, and treated. 129 (77%) were acetylcholine receptor antibody-positive. Of
these patients, more of those in the efgartigimod group were MG-ADL responders (44 [68%] of 65) in cycle 1 than in
the placebo group (19 [30%] of 64), with an odds ratio of 4·95 (95% CI 2·21–11·53, p<0·0001). 65 (77%) of 84 patients
in the efgartigimod group and 70 (84%) of 83 in the placebo group had treatment-emergent adverse events, with the
most frequent being headache (efgartigimod 24 [29%] vs placebo 23 [28%]) and nasopharyngitis (efgartigimod ten
[12%] vs placebo 15 [18%]). Four (5%) efgartigimod-treated patients and seven (8%) patients in the placebo group had a
serious adverse event. Three patients in each treatment group (4%) discontinued treatment during the study. There
were no deaths.
Interpretation Efgartigimod was well tolerated and efficacious in patients with generalised myasthenia gravis. The
individualised dosing based on clinical response was a unique feature of ADAPT, and translation to clinical practice
with longer term safety and efficacy data will be further informed by the ongoing open-label extension.
Funding argenx.
Copyright © 2021 Elsevier Ltd. All rights reserved.
Introduction Most patients with generalised myasthenia gravis
Generalised myasthenia gravis is a rare, chronic, auto­ (about 85%) have IgG autoantibodies, most often directed
immune disease that causes debilitating and potentially against the skeletal muscle nicotinic acetylcholine receptor
life-threatening muscle weakness affecting ocular motility, and less frequently against muscle-specific tyrosine kinase
swallowing, speech, mobility, and respiratory function, (MUSK) and low-density lipoprotein receptor-related
which can significantly impair independence and quality protein 4 (LRP4).2,3 A small proportion of patients have no
of life.1 identifiable antibodies. These autoantibodies exert a direct
www.thelancet.com/neurology Vol 20 July 2021

Research in context
Evidence before this study
We searched PubMed up to Nov 5, 2020, for relevant clinical
studies in generalised myasthenia gravis, with no language
restrictions. Key search terms included “neonatal Fc receptor”,
“IgG recycling”, “antibody fragment”, and “autoantibody
reduction”. Although preclinical and early-phase studies had
been completed with some neonatal Fc receptor antagonists,
we found no phase 3 studies in generalised myasthenia gravis.
Additionally, although therapeutic plasma exchange had shown
the effect of IgG reduction, there were no previous
pharmacological approaches to achieving such a targeted
reduction in IgG. Finally, many of the studies in myasthenia
gravis had been constrained by other factors, such as only
including patients who have acetylcholine receptor
autoantibodies.
Added value of this study
Although there are treatment options available to patients with
generalised myasthenia gravis, they are frequently
burdensome, have substantial side-effects, do not alleviate
symptoms, or are reserved for refractory patients. ADAPT was
the largest clinical trial in patients with generalised myasthenia
gravis and the only one to include patients regardless of their
pathogenic effect in generalised myasthenia gravis and
their mechanisms of action include functional blockade,
accelerated internali­ sation, and degradation of acetyl­
choline receptors and activation of complement.4–7 These
actions lead to reduced density of functional acetylcholine
receptors and damage to the neuromuscular junction,
resulting in impaired neuromuscular transmission.4–7 Most
acetylcholine recep­tor and LRP4 antibodies are of the IgG1
subtype, which can activate complement, whereas the
IgG4 subtype, which includes MUSK antibodies, do not.2,8–10
Existing treatments, including corticosteroids and non-
steroidal immunosuppressive therapies (NSISTs), broadly
suppress the immune system and do not selectively
target IgG autoantibodies that are central to generalised
myasthenia gravis pathophysiology.7 Moreover, these
treat­ments frequently provide insufficient symptom relief
and are associated with burdensome side-effects such as
glucose intolerance, weight gain, arterial hypertension,
osteoporosis, gastrointestinal issues, bradycardia, and
renal dysfunction, which can limit their use.7 Another
therapeutic approach has been to block complement
activation, targeting one of the downstream pathogenic
pathways triggered specifically by acetylcholine receptor
antibodies.11,12 Overall, there remains a significant unmet
need for generalised myasthenia gravis treatment options
that are effective, targeted, well tolerated, and can be used
in a broad population of patients.2,13,14
The neonatal Fc receptor (FcRn) is an MHC class I-like
molecule that recycles IgG, extending its half-life by about
four times that of other immunoglobulins that are not
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Articles
University Medical Center,
Leiden, Netherlands
(Prof J Verschuuren MD);
autoantibody status. During the 26-week study, efgartigimod Department of
was well tolerated, with most adverse events being either mild Neuroimmunology and
or moderate in severity. Additionally, significantly more Neuromuscular Diseases,
Fondazione Istituto
patients in the efgartigimod group than in the placebo group Neurologico Carlo Besta, Milan,
had clinically meaningful improvements in their Myasthenia Italy (R Mantegazza MD)
Gravis Activities of Daily Living and Quantitative Myasthenia Correspondence to:
Gravis scores. Prof James F Howard Jr,
Department of Neurology,
Implications of all the available evidence The University of North Carolina
The study used four validated myasthenia gravis-specific at Chapel Hill, Chapel Hill,
NC 27599, USA
outcome measures, utilising both patient-reported and
howardj@neurology.unc.edu
physician-reported information, to assess the effects of
See Online for appendix
efgartigimod in patients with generalised myasthenia gravis.
Notably, the primary and some secondary endpoints required
patients to have a clinically meaningful improvement in the
associated outcome measure, and for this improvement to
persist for at least 4 weeks. The data suggest that reduction of
pathogenic IgG antibodies through inhibition of neonatal Fc
receptor recycling might be an effective approach to the
treatment of a broad population of generalised myasthenia
gravis and should encourage research in other IgG-mediated
autoimmune diseases.
recycled by FcRn (eg, IgM or IgA).15 Following cellular
uptake, the Fc region of an IgG antibody binds two FcRn
receptors under acidic conditions in the endosome.16 IgGs
bound to FcRn are rescued from lysosomal degradation
and released at physiological pH outside the cell.17–20
Therefore, FcRn perpetuates the availability of IgG auto­
antibodies in IgG-mediated diseases such as generalised
myasthenia gravis. The utility of removing autoantibodies
in generalised myasthenia gravis has been demonstrated
by the effectiveness of plasma exchange and immuno­
adsorption; however, their use is limited by availability
and requirement for specialised facilities.21 Blocking
FcRn is a rational therapeutic approach to target the key
pathogenic driver in generalised myasthenia gravis.
Efgartigimod (ARGX-113) is a human IgG1 antibody
Fc-fragment, a natural ligand of FcRn, that has been
engineered for increased affinity to FcRn compared with
endogenous IgG while retaining the characteristic pH
dependence.22 It outcompetes endogenous IgG binding,
thereby reducing IgG recycling and increasing IgG
degrada­tion.22 In phase 1 and 2 trials, efgartigimod
significantly reduced concentrations of all IgG subtypes
without decreasing levels of other immunoglobulins
or albumin, which is also recycled by FcRn.22,23 These
reductions were associated with clinically meaningful and
sustained improvements in generalised myasthenia gravis
symptoms and activities of daily living. The phase 3
ADAPT study aimed to assess the safety and efficacy of
efgartigimod, in patients with generalised myasthenia
gravis.23
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Methods
Study design
ADAPT was a randomised, double-blind, placebo-
controlled, multicentre, phase 3 trial of efgartigimod in
patients with generalised myasthenia gravis. Patients were
recruited from 56 neuromuscular academic and com­
munity centres across Japan and 14 countries in Europe
and North America (appendix pp 2–11). Independent
ethics committees and international review boards
provided written approval for the study protocol and all
amendments. The trial was conducted according to the
principles outlined in the Declaration of Helsinki.
Participants
Patients aged at least 18 years with generalised myasthenia
gravis, with or without acetylcholine receptor antibodies,
were eligible if their disease was categorised as Myasthenia
Gravis Foundation of America class II to IV and they had a
Myasthenia Gravis Activities of Daily Living (MG-ADL)
score of at least 5 (with >50% of the MG-ADL score due
to non-ocular symptoms). Diagnosis was supported by
a history of abnormal neuro­muscular transmission tests, a
positive edrophonium chloride test, or improvement with
acetylcholinesterase inhibitors. Eligibility criteria also
required patients to be on a stable dose of at least one
treatment for generalised myasthenia gravis (ie, acetylcho­
linesterase inhibitors, corticosteroids, or NSISTs) before
screening and through­out the trial. There was no require­
ment for specific generalised myasthenia gravis therapies.
Patients were excluded if they had received rituximab or
eculizumab in the 6 months before screening, undergone
thymectomy within 3 months, had intravenous immuno­
globulin or plasma exchange within 1 month of screening,
had active hepatitis B, were seropositive for hepatitis C,
seropositive for HIV with low CD4 count, had serum IgG
levels less than 6 g/L at screening, or were pregnant.
A complete list of inclusion and exclusion criteria is in the
appendix (pp 11–12). Potential patients were recruited
through the investigators’ practice or via physician referral.
All patients provided written informed consent before
starting the study.
Randomisation and masking
Patients were randomly assigned in a 1:1 ratio to either
efgartigimod or placebo. Placebo was matched to
efgartigimod in appearance and supplied in identical con­
tainers. Randomisation was performed centrally using
interactive response technology, using both web and voice
systems, by an independent company (SGS, Zwijnaarde,
Belgium) that held randomisation codes until after the
final database lock. Randomisation was based on three
stratification factors: acetylcholine receptor antibody
status (positive vs negative), NSISTs (taking vs not taking),
and Japanese nationality (yes vs no). The stratification
factors were selected to ensure con­sistency of effect across
antibody status, concomitant medication, and ethnic­
ities. Due to the small number of patients anticipated
528
at individual centres, randomisation was done across,
rather than within, the centres. Investi­gators, patients,
study person­nel, clinic staff, and the funder remained
masked to treatment assignments for the duration of
the study.
Procedures
Patients were screened for the study during a 2-week
period, which was followed by a 26-week treatment period.
Efgartigimod (10 mg/kg) or matching placebo was
administered as four infusions per cycle (one infusion per
week). After each cycle there was a period of at least
5 weeks of follow-up. All patients received an initial
cycle, with subsequent cycles administered according to
individual clinical response when MG-ADL score was at
least 5 (with >50% MG-ADL non-ocular) and, if the patient
was an MG-ADL responder, when they no longer had a
clinically meaningful decrease (MG-ADL clinically mean­
ing­ful improvement defined as having ≥2-point improve­
ment in total MG-ADL score) compared with baseline.
Subsequent cycles could commence no sooner than
8 weeks from initiation of the previous cycle; a maximum
of three cycles were possible in the 26-week study. Patients
who required rescue therapy were discon­ tinued from
study treatment. Patients who completed the study or
could not complete a cycle before study end (retreatment
after day 126) were able to rollover to the ongoing open-label
extension study (ADAPT+; NCT03770403).
Efficacy was assessed with the MG-ADL scale
(patient-reported, physician-recorded outcome measure);24
Quantitative Myasthenia Gravis (QMG) score (physi­cian
assessed, including quanti­­ta­tive measures; clinically mean­
ing­ful improvement ≥3-point reduction),25 Myasthenia
Gravis Composite (MGC) scale (patient and physician
assessed; clinically meaning­ ful improvement ≥3-point
reduction);26 the 15-item revised version of the Myasthenia
Gravis Quality of Life (MG-QOL15r)27 question­­naire
(patient completed), and EQ5D quality of life scale (patient
completed).
Assessments were done weekly for 8 weeks after initia­
tion of each cycle and then every 2 weeks up to 26 weeks.
Pharmacodynamic effects were analysed using
validated assays of total IgG, IgG subtypes (IgG1, IgG2,
IgG3, and IgG4), and autoantibodies (anti-acetylcholine
receptor antibodies for the acetylcholine receptor
antibody-positive patients and antibodies against MUSK
for the MUSK antibody-positive patients). The validated
assays were a radioimmunoassay (IBL International,
Hamburg, Germany) that used acetylcholine receptor
labelled with ¹²⁵I-α-bungarotoxin for anti-acetylcholine
receptor antibodies and an ELISA (IBL International) for
anti-MUSK antibodies.
Outcomes
The primary efficacy endpoint was the proportion of
acetylcholine receptor antibody-positive patients who were
MG-ADL responders in the first treatment cycle. An
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MG-ADL responder was defined as a patient who had at
least a 2-point improvement (reduction) in MG-ADL
score, sustained for at least 4 consecutive weeks, with the
first improvement occurring by week 4 of the cycle (1 week
after the fourth infusion). Secondary endpoints were
assessed in hierarchical order, as follows: (1) proportion of
QMG responders (defined as a ≥3 point improvement in
the total QMG score for ≥4 consecutive weeks with the
first improvement occurring by week 4 of cycle 1) in
the acetylcholine receptor antibody-positive population; (2)
percentage of MG-ADL responders in cycle 1 in the overall
population (ie, acetylcholine receptor antibody-positive
and antibody-negative patients); (3) proportion of time
patients showed a clinically meaningful improve­ment in
MG-ADL score in the acetylcholine receptor antibody-
positive population, up to day 126; (4) time from
day 28 (1 week after the fourth infusion in cycle 1) to
not having clinically meaningful improvement in the
acetylcholine receptor antibody-positive population; and
(5) proportion of early MG-ADL responders in cycle 1
(MG-ADL responders with first MG-ADL improvement of
≥2 points occurring by week 2) in the acetylcholine
receptor antibody-positive population.
Safety was assessed through incidence of adverse events
and changes in clinical laboratory values and vital signs,
and on electrocardiograms. Tertiary endpoints were
pharma­co­dynamics and immunogenicity.
Predefined exploratory endpoints assessed time to onset
of effect; magnitude of effect, including proportion of
patients achieving minimal symptom expression (defined
as MG-ADL score of 0 or 1) and proportion of patients
with increasing levels of MG-ADL and QMG score
improve­ ment in each cycle; duration of response in
MG-ADL responders; repeatability of effect with second
treatment cycle; and the change in Myasthenia Gravis
Composite and MG-QOL15r scores.
Statistical analysis
The proportion of MG-ADL responders in the placebo
group was hypothesised to be 30%. The treatment
difference was assumed to be 35% for acetylcholine
receptor antibody-positive patients and 5% for acetyl­
choline receptor antibody-negative patients. A difference
of total MG-ADL responder rate of 35% between
the placebo and efgartigimod primary acetylcholine
recep­tor antibody-positive population is considered
clinically relevant. In the phase 2 ARGX-113-1602 study,23
the total MG-ADL responder rate was 33% for placebo
(three of 12) and 75% (nine of 12) for efgartigimod.
Sample size was based on allowing enrolment of up to
20% acetylcholine receptor antibody-negative patients.
Based on this quota, a sample size of 150 provided power
of 96% in the primary population of acetylcholine
receptor antibody-positive patients to detect a difference
of 35% in the proportion of responders with 120 patients.
The sample size also provided a power of 90% to detect a
29% difference in the proportion of responders in the
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216 patients screened
49 ineligible
32 did not meet inclusion criteria
1 sponsor decision
2 withdrew consent
11 seronegative cap reached
3 other*
167 patients enrolled
84 randomly assigned to efgartigimod 83 randomly assigned to placebo
84 received efgartigimod 83 received placebo
4 discontinued in first treatment cycle 9 discontinued in first treatment cycle
2 adverse event 3 adverse event
1 protocol deviation 1 prohibited medications
1 rescue therapy 2 rescue therapy
1 sponsor decision
2 patient withdrew
80 completed first treatment cycle 74 completed first treatment cycle
1 discontinued in second treatment cycle, 1 discontinued in second treatment cycle,
adverse event patient withdrew
79 completed treatment 73 completed treatment
Figure 1: Trial profile
*Absence of laboratory results on the day before the final day of the screening period.
overall population with a two-sided α level of 5%, allowing
for a 10% dropout rate.
Efficacy analyses were done in the modified intention-
to-treat population, including all randomly assigned
patients who had a valid baseline MG-ADL assessment
and at least one post-baseline MG-ADL assessment.
Safety analyses were done in all patients who received at
least one dose or part of a dose. Patients were discontinued
from treatment if they became pregnant, received rescue
therapy (plasma exchange, intravenous immunoglobulin,
immunoadsorption, any new type of corticosteroid, or
increased dose of current steroid; rescue was permitted
per protocol in case of new or worsening respiratory or
bulbar symptoms or at least 2-point increase of individual
non-ocular MG-ADL items), developed a serious adverse
event that could jeopardise the safety of the patient, or
developed a bacterial, viral, or fungal infection (evaluated
on a case-by-case basis). After discontinuation, patients
who did not withdraw con­sent were followed up for safety
and disease severity assessments through the rest of
the trial.
Statistical analyses were done using SAS, version 9.2 or
higher, and the software package R, where applicable. The
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Percentage of time patients showed a clinically meaningful

All patients Acetylcholine receptor
antibody-positive patients improve­ ment in MG-ADL score in the acetylcholine
receptor antibody-positive population was analysed using
Efgartigimod Placebo Efgartigimod Placebo
group group group group an ANCOVA model. In this analysis, randomised treat­
(n=84) (n=83) (n=65) (n=64) ment group and the stratifica­tion variables were included
Age, years 45·9 (14·4) 48·2 (15·0) 44·7 (15·0) 49·2 (15·5) as factors, and baseline total MG-ADL score was included
Sex as a covariate. Time from day 28 to not having clinically
Female 63 (75%) 55 (66%) 46 (71%) 40 (63%) meaningful improvement in the acetylcholine receptor
Male 21 (25%) 28 (34%) 19 (29%) 24 (38%)
antibody-positive population was estimated using Kaplan-
Race
Meier time-to-event analysis and compared by means of
Asian 9 (11%) 7 (8%) 7 (11%) 4 (6%)
a stratified log-rank test, stratified for the stratification
variables. Additional endpoints assessing efficacy, safety,
Black or African American 3 (4%) 3 (4%) 1 (2%) 3 (5%)
pharmacodynamics, and immunogenicity were analysed
White 69 (82%) 72 (87%) 54 (83%) 56 (88%)
in a descriptive manner. This study is registered at
Other* 3 (4%) 1 (1%) 3 (5%) 1 (2%)
ClinicalTrials.gov (NCT03669588).
Time since generalised myasthenia gravis 10·1 (9·0) 8·8 (7·6) 9·7 (8·3) 8·9 (8·2)
diagnosis, years
MGFA class at screening Role of the funding source
II 34 (40%) 31 (37%) 28 (43%) 25 (39%)
The funder of the study had a role in study design, data
III 47 (56%) 49 (59%) 35 (54%) 36 (56%)
collection, data interpretation, data analysis, and writing
IV 3 (4%) 3 (4%) 2 (3%) 3 (5%)
of the report.
Previous thymectomy 59 (70%) 36 (43%) 45 (69%) 30 (47%)
Acetylcholine receptor antibody-positive 65 (77%) 64 (77%) 65 (100%) 64 (100%)
Results
216 patients were screened between Sept 5, 2018, and
MUSK antibody-positive 3 (4%) 3 (4%) 0 0
Nov 26, 2019, of whom 167 (84 in the efgartigimod group
Acetylcholine receptor or MUSK antibody- 16 (19%) 16 (19%) 0 0
negative and 83 in the placebo group) were enrolled, randomly
Total MG-ADL score 9·2 (2·6) 8·8 (2·3) 9·0 (2·5) 8·6 (2·1) assigned, and treated (figure 1). 129 (77%) were acetyl­
Total Quantitative Myasthenia Gravis score 16·2 (5·0) 15·5 (4·6) 16·0 (5·1) 15·2 (4·4) choline receptor antibody-positive and 38 (23%) were
Total Myasthenia Gravis Composite score 18·8 (6·1) 18·3 (5·5) 18·6 (6·1) 18·1 (5·2)
acetylcholine receptor antibody-negative, of whom six (4%)
Total MG-QOL15r score 16·1 (6·4) 16·8 (5·7) 15·7 (6·3) 16·6 (5·5)
were MUSK antibody-positive. There were five treatment
At least one previous NSIST 62 (74%) 57 (69%) 47 (72%) 43 (67%)
discontinuations in the efgartigimod group and ten in the
Myasthenia gravis therapy at baseline
placebo group.
Patient characteristics were representative of the
Any steroid 60 (71%) 67 (81%) 46 (71%) 51 (80%)
general generalised myasthenia gravis population and
Any NSIST 51 (61%) 51 (61%) 40 (62%) 37 (58%)
were well balanced between the efgartigimod and placebo
Steroid and NSIST 43 (51%) 44 (53%) 34 (52%) 31 (48%)
groups (table 1), except more patients in the efgartigimod
No steroid or NSIST 16 (19%) 7 (8%) 13 (20%) 6 (9%)
group had previously undergone thymectomy than in the
Data are mean (SD) or n (%). MG-ADL=Myasthenia Gravis Activities of Daily Living. MGFA=Myasthenia Gravis placebo group. The mean time since thymectomy in
Foundation of America. MG-QOL15r=15-item revised version of the Myasthenia Gravis Quality of Life.
NSIST=non-steroidal immunosuppressant therapy. *Includes American Indian or Alaska Native (n=2) and multiple these patients was 10·84 (SD 9·0) years.
(n=1) for the efgartigimod group, and not reported for the placebo group (n=1). Most patients (144 [86%] of 167) were receiving
immunosuppressive treatment (steroids or NSISTs).
Table 1: Baseline demographic and clinical characteristics
48 (29%) had never previously been treated with an
NSIST. The mean baseline MG-ADL and QMG scores
primary endpoint was tested by means of a two-sided exact demonstrate substantial disease burden despite ongoing
test using a logistic regression model with baseline total generalised myasthenia gravis treatment.
score as a covariate and the three stratification factors as The number of cycles of assigned treatment received by
variables. The treatment effect was presented as an odds patients during the study is in the appendix (p 13). In
ratio (OR) with 95% CI and two-sided p value. If the efgartigimod-treated patients, the median duration of
primary endpoint met significance at the 5% two-sided cycle 1 (time from first infusion in cycle 1 until first
α level, secondary endpoints were tested at a 5% two-sided infusion in cycle 2 or final visit of study) was 10 weeks
significance level in hierarchical order using a fixed- (IQR 71–113 days) and for placebo-treated patients, the
sequence approach. The secondary endpoints of QMG median duration was 10 weeks (71–141 days).
responders in cycle 1 in the acetylcholine receptor A significantly higher proportion of acetylcholine
antibody-positive population, MG-ADL responders in receptor antibody-positive patients in the efgartigimod
cycle 1 in the overall population, and percentage of early group (44 [68%] of 65) were MG-ADL responders in cycle 1
MG-ADL responders in cycle 1 in the acetylcholine receptor (primary endpoint) than in the placebo group (19 [30%]
antibody-positive population were tested using the same of 64; OR 4·95 [95% CI 2·21–11·53], p<0·0001; table 2).
logistic regression model as for the primary endpoint. Additionally, a significantly greater proportion of patients

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Efgartigimod group Placebo group OR (95% CI) p value

MG-ADL responder in cycle 1 (primary endpoint) 44/65 (68%) 19/64 (30%) 4·95 (2·21–11·53) <0·0001
Quantitative Myasthenia Gravis responder in cycle 1 41/65 (63%) 9/64 (14%) 10·84 (4·18–31·20) <0·0001
MG-ADL responder in cycle 1 (all patients) 57/84 (68%) 31/83 (37%) 3·70 (1·85–7·58) <0·0001
Percentage of time with ≥2-point improvement in MG-ADL up to day 126 48·7% 26·6% ·· 0·0001
Median time from day 28 until no clinically meaningful improvement, days 35 (18–71) 8 (1–57) ·· 0·26
Early MG-ADL responder (cycle 1) 37/65 (57%) 16/64 (25%) ·· Not assessed*
Data are n/N (%), or median (IQR), unless stated otherwise. Analyses were done in acetylcholine receptor antibody-positive patients unless otherwise stated.
MG-ADL=Myasthenia Gravis Activities of Daily Living. *Secondary endpoints were tested in hierarchical order. The fifth secondary endpoint was not assessed because the
fourth secondary endpoint was not significant.

Table 2: Summary of primary and secondary endpoints

A B
0
Mean change in Quantitative Myasthenia Gravis score

–1 –1
Mean change in MG-ADL score

–2
–2
–3
* * *
–3 –4

–5
*
–4 * *
* *
–6
* Efgartigimod group *
*
–5 * Placebo group –7
* * *

C D
0 0
Mean change in Myasthenia Gravis Composite scale

–1 –1
–2
–2
Mean change in MG-QOL15r

–3
–3
–4
*
–5 * –4

–6 –5
–7 *
–6
–8 * *
* –7
–9 * *
*
–8 *
–10 *
* *
* *
–11 –9
0 1 2 3 4 5 6 7 8 10 0 1 2 3 4 5 6 7 8 10
Time since baseline (weeks) Time since baseline (weeks)

Figure 2: Change in MG-ADL (A), Quantitative Myasthenia Gravis score (B), Myasthenia Gravis Composite scale (C), and MG-QOL15r (D) during cycle 1,
in acetylcholine receptor antibody-positive patients
Error bars show standard error. MG-ADL=Myasthenia Gravis Activities of Daily Living. MG-QOL15r=15-item revised version of the Myasthenia Gravis Quality of Life
questionnaire. *p<0·05.

in the efgartigimod group (41 [63%] of 65) were QMG sustained through week 7 in all measures (figure 2). The
responders in cycle 1 than in the placebo group (nine [14%] maximum improvement in efgartigimod treated patients
of 64; OR 10·84 [95% CI 4·18–31·20], p<0·0001; table 2). occurred at week 5 for MG-QOL15r and week 4 for other
Patients in the efgartigimod group had greater total measures.
mean score improvements in MG-ADL, QMG, MCG, and A greater proportion of patients in the efgartigimod
MG-QOL15r in cycle 1, with statistically significant group than in the placebo group achieved higher levels of
differences from baseline observed from week 1 and improvement in MG-ADL (up to 9-point reduction) and

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 Articles

(1–57) with placebo (p=0·26 log-rank test; table 2).

A
9 14·3%
Minimum improvement in MG-ADL score
Efgartigimod group
Although a log-rank test was not significant, a Wilcoxon
0% Placebo group test done post hoc was significant (p=0·013).
Among cycle 1 MG-ADL responders, the duration of
responder status was 6–7 weeks in 14 (32%) of 44 patients,

8 20·6% 1·7%
8–11 weeks in ten (23%) patients, and 12 weeks or more
7 27·0% 3·3%
in 15 (34%) patients (data not shown).
6 39·7% 8·3%
In patients who received a second cycle, a greater
proportion of patients in the efgartigimod group (36 [71%]
5 55·6% 11·7% of 51) were MG-ADL responders compared with the
placebo group (11 [26%] of 43), with similar rates to cycle 1.
4 63·5% 23·3% Similar to cycle 1, there was a greater total mean score
improvement in MG-ADL and QMG in the efgartigimod
3 73·0% 36·7%
group than in the placebo group in the second treatment
2 77·8% 48·3% cycle (data not shown). Of the 44 acetylcholine receptor
antibody-positive patients in the efgartigimod group
who were MG-ADL responders in cycle 1, 32 qualified
B for retreatment and 29 (90%) of these were MG-ADL
10 25·8% 0%
responders again in cycle 2. Among 21 patients in the
efgartigimod group who were not MG-ADL responders
9 33·9% 0% during cycle 1, 19 were retreated and seven (37%) of these
Minimum improvement in Quantitative

were MG-ADL responders in cycle 2. Six (86%) of seven

8 37·1% 1·7% patients in the efgartigimod group who received a third
Myasthenia Gravis score

cycle were MG-ADL responders (data not shown).

7 45·2% 1·7%
Predefined exploratory analyses did not show any
6 50·0% 5·2% efficacy differences based on gender, age, or baseline
MG-ADL (data not shown). Concomitant use of NSISTs
5 59·7% 12·1% also did not affect efficacy, with 18 (72%) MG-ADL
responders of the 25 acetylcholine receptor antibody-
4 64·5% 15·5%
positive patients in the efgartigimod group who were
3 74·2% 25·9%
not on NSISTs. Of the 45 acetylcholine receptor antibody-
positive efgartigimod-treated patients with previous
100 80 60 40 30 0 20 40 60 80 100 thymectomy, 27 (60%) were MG-ADL responders, com­
Cumulative percentage pared with 17 (85%) of 20 patients who had not previously
Figure 3: Minimum point improvement in MG-ADL (A) and Quantitative Myasthenia Gravis (B) score in
undergone thymectomy.
cycle 1, in acetylcholine receptor antibody-positive patients Results in the overall population were similar to those in
Minimum improvements 1 week after the last infusion of cycle 1 (week 4). MG-ADL=Myasthenia Gravis Activities the acetylcholine receptor antibody-positive population,
of Daily Living. including significantly more patients in the efgartigimod
group (57 [68%] of 84) who were MG-ADL responders in
QMG (up to 10-point reduction) score at week 4 (figure 3). cycle 1 than in the placebo group (31 [37%] of 83; OR 3·70
26 (40%) of 65 patients in the efgartigimod group attained [95% CI 1·85–7·58], p<0·0001; table 2).
an MG-ADL score of 0 or 1 (minimal symptom expres­ Predefined exploratory analyses showed that in
sion) in cycle 1 compared with seven (11%) of 63 in the acetylcholine receptor antibody-negative patients, there
placebo group (p<0·0001). was a similar number of MG-ADL responders in each
More patients in the efgartigimod group than the treatment group in cycle 1: 13 (68%) of 19 patients in the
placebo group were early MG-ADL responders (table 2). efgartigimod group versus 12 (63%) of 19 in the placebo
In the 44 acetylcholine receptor antibody-positive group. There were more QMG responders in the
MG-ADL responders in the efgartigimod group, the onset efgartigimod group than in the placebo group in cycle 1:
of response occurred by week 2 in 37 (84%) patients. ten (53%) versus seven (37%) patients. Six (32%) patients
Efgartigimod-treated patients showed a clinically in the efgartigimod group achieved minimal symptom
meaningful improvement in MG-ADL score for 48·7% of expression in cycle 1 versus three (16%) in the placebo
the time between start of study and day 126, compared group (data not shown).
with 26·6% of the same period in the placebo group A post-hoc analysis of acetylcholine receptor antibody-
(p=0·0001; table 2). negative patients assessed the proportion of patients who
The median time from day 28 to not having clinically were both MG-ADL and QMG responders in cycle 1:
meaningful improvement over the course of the study nine (47%) of 19 patients in the efgartigimod group
was 35 days (IQR 18–71) with efgartigimod and 8 days and four (21%) of 19 in the placebo group. Among the

532 www.thelancet.com/neurology Vol 20 July 2021

 Articles

acetylcholine receptor antibody-negative patients, six were

Efgartigimod group Placebo group
MUSK antibody-positive, three in each treatment group. (n=84) (n=83)
All six patients were MG-ADL responders in cycle 1.
Any adverse event 65 (77%) 70 (84%)
In acetylcholine receptor antibody-positive patients,
Any serious adverse event 4 (5%) 7 (8%)
there were mean maximum reductions of 61·3% (SD 0·9)
Any adverse event leading to 3 (4%) 3 (4%)
in IgG and 57·6% (1·3) in acetylcholine receptor anti­ discontinuation of study drug
bodies, 1 week after the fourth infusion in cycle 1 Any infection 39 (46%) 31 (37%)
(appendix p 14). Levels returned to baseline by week 12 Infusion-related reaction event 3 (4%) 8 (10%)
(9 weeks after the last infusion of cycle 1). Reductions
Most common adverse events
were similar across subtypes, with mean maximum
Headache 24 (29%) 23 (28%)
reductions of 68% (1·0) for IgG1, 60% (1·7) for IgG2,
Nasopharyngitis 10 (12%) 15 (18%)
63% (1·2) for IgG3, and 52% (1·7) for IgG4. Similar
Nausea 7 (8%) 9 (11%)
reductions in IgG and acetylcholine receptor antibodies
Diarrhoea 6 (7%) 9 (11%)
were seen with each treatment cycle. However, no
Upper respiratory tract 9 (11%) 4 (5%)
reductions in albumin levels were observed. infection
No deaths occurred during the study in either the Urinary tract infection 8 (10%) 4 (5%)
efgartigimod or placebo groups. 65 (77%) of 84 patients in
Data are n (%).
the efgartigimod group and 70 (84%) of 83 in the placebo
group had adverse events, with the most frequent being Table 3: Summary of adverse events in all patients
headache, nasopharyngitis, nausea, diarrhoea, upper
respiratory tract infections, and urinary tract infections
(table 3). Incidence of headache was similar between with generalised myasthenia gravis were consistent across
groups; nausea, diarrhoea, and nasopharyngitis occurred four myasthenia gravis-specific scales, and these benefits
in more placebo patients, and upper respiratory tract were observed early and were reproducible and durable.
infections and urinary tract infections occurred in more The study enrolled a broad population of patients
efgartigimod patients. Most adverse events were mild or with generalised myasthenia gravis, including both
moderate in severity, with nine (11%) patients with severe antibody-positive and acetylcholine receptor antibody-
events in the efgartigimod group and eight (10%) in the negative patients, with no requirement for patients to
placebo group. Four (5%) efgartigimod-treated patients have had specific myasthenia gravis medication. Most
had a serious adverse event, which were thrombocytosis, patients were receiving steroids or NSISTs; however,
rectal adenocarcinoma, myasthenia gravis worsening about 30% had not previously received an NSIST.
(each leading to treatment discontinuation), and depres­ At enrolment, despite ongoing myasthenia gravis
sion. In the placebo group, seven (8%) patients had a therapy, patients still had poor scores on the myasthenia
serious adverse event, including one case each of myo­ gravis strength and function scales. Treatment with
cardial ischaemia, atrial fibrillation, and spinal ligament efgartigimod provided significant, clinically meaningful,
ossification, which all led to treatment discontinuation. and durable clinical benefit to most of these patients.
The remaining events were upper respiratory infec­ Many patients had improvement beyond the clinically
tion, spinal compression fracture, myasthenia gravis meaningful threshold, achieving up to 9-point reductions
worsening, and myasthenia gravis crisis. Adverse events in MG-ADL and 10-point reductions in QMG. Minimal
related to infections occurred in 39 (46%) patients in symptom expression was achieved by 40% of acetyl­choline
the efgartigimod group and 31 (37%) in the placebo receptor antibody-positive efgartigimod-treated patients.
group. All infections were reported as mild-to-moderate Most patients had a clinically meaningful improvement in
severity except for three severe events, which were MG-ADL within 2 weeks of starting treatment. Although
influenza and pharyngitis in the efgartigimod group and 68% of acetylcholine receptor antibody-positive patients
upper respiratory tract infections in the placebo group. were MG-ADL responders with the first treatment cycle,
Infusion-related reactions were reported in three (4%) 78% of patients achieved this status during the study with
patients in the efgartigimod group and eight (10%) in the further treatment cycles.
placebo group, all mild in severity. There were no clin­ The early onset of action, observed benefit in patients
ically meaningful changes in haematology or chemistry with or without previous NSIST exposure, and the
parameters (including no decrease in albumin levels), favourable tolerability profile suggest that efgartigimod
electrocardiograms, or vital signs in either group. might be able to be used throughout disease continuum
of patients with generalised myasthenia gravis. Acetyl­
Discussion choline receptor antibodies cause a net reduction of
The ADAPT phase 3 trial showed that efgartigimod was functional acetylcholine receptors at the postsynaptic
well tolerated and efficacious in patients with generalised membrane. However, patients with general­ ised myas­
myasthenia gravis. The reduction in disease burden and thenia gravis also have increased acetylcholine receptor
improvement in strength and quality of life in patients synthesis and repopulation, shown through mRNA and

www.thelancet.com/neurology Vol 20 July 2021 533

 Articles
protein production, presumably as compen­satory mech­
anisms.28,29 Because of this, the reduction of acetylcholine
receptor antibodies by efgartigimod after one infusion
could lead to a corresponding increase in acetylcholine
receptors at the postsynaptic membrane and potentially
account for the early onset of effect.
Although more patients in the efgartigimod group had
previously undergone thymectomy, a post-hoc analysis
showed that the proportion of patients who were MG-ADL
responders was lower in patients with previous thymec­
tomy. Therefore, the increased prevalence of thymectomy
in the efgartigimod group did not appear to favour
efgartigimod.
This phase 3 study tested efgartigimod adminis­
tered in treatment cycles, with the frequency of cycles
defined by the duration of clinical effect in each patient.
This individualised approach to treatment according to
patient’s need proved effective, with reproducible efficacy
after a second and third cycle.
A third of acetylcholine receptor antibody-positive
MG-ADL responders maintained a clinically meaningful
improvement in MG-ADL score for more than 12 weeks,
suggesting that a proportion of patients have clinical
benefit beyond the reduction in IgG and acetylcholine
receptor antibodies. Production of sufficient acetylcholine
receptor to restore the safety factor for neurotransmission
might explain the prolonged effect in some patients, with
appropriate reserves established to maintain neurotrans­
mission even after return of acetylcholine receptor
antibodies to normal levels.30
The secondary endpoint of time from day 28 of cycle 1
(1 week after the last infusion) until the patient not having
a clinically meaningful improvement was numerically
greater in the acetylcholine receptor antibody-positive
efgartigimod group than placebo (35 days compared to
8 days); however, it was not significant (log-rank test,
p=0·26). The log-rank test was not the most appropriate
test, because the data did not show proportional hazards.
Patients were likely to require retreatment at some point
in the future so the chance of the event occurring was not
equal throughout the duration of the study.
68% of acetylcholine receptor antibody-negative
efgartigimod-treated patients had a response, similar to
that in acetylcholine receptor antibody-positive patients,
but there was an unexpectedly high response rate in the
placebo group. A post-hoc analysis of acetylcholine
receptor antibody-negative patients who were both
MG-ADL and QMG responders in cycle 1 showed a treat­
ment effect, suggesting efgartigimod might be effective in
this patient population. There were only six patients with
anti-MUSK antibodies, three in each treatment group,
and all six were MG-ADL responders in cycle 1. Further
information regarding the efficacy in acetylcholine
receptor antibody-negative patients will be gained in the
ongoing open-label extension trial.
Efgartigimod reduced IgG levels in acetylcholine recep­
tor antibody-positive patients, with similar reductions
534
with each cycle and across IgG subtypes and a similar
reduction in the antibody-negative patients. The reduction
in acetylcholine receptor autoantibodies was similar to
that of IgG, and both paralleled the improve­ments in
symptoms. This showed that selective removal of IgG is
an effective treatment approach in generalised myasthenia
gravis, which is in line with the data available from
plasma exchange, a treatment that removes auto­ anti­
bodies and is considered highly efficacious but is limited
by its administrative challenges.
Existing treatments for generalised myasthenia gravis
are associated with burdensome short-term and long-
term side-effects that can limit their use. Efgartigimod
was well tolerated in this study, with most adverse events
mild or moderate in severity and low incidence of
infusion reactions. Although headache was the most
common adverse event, it occurred in equal numbers of
patients in both treatment groups. Efgartigimod did not
reduce albumin levels, demonstrating its selectivity for
the IgG binding site of FcRn and suggesting that it does
not alter the function of FcRn.
The rate of infections is of special interest because
patients with myasthenia gravis are predisposed to infec­
tions, probably exacerbated by concomitant immuno­
suppressive treatments.31,32 In the efgartigimod-treated
group, 46% of patients had an infection compared with
37% in the placebo group. Most infections were mild
to moderate, with only two graded as severe in the
efgartigimod-treated patients. Although longer term data
are required to assess the risk of infection, these results
are reassuring. Additionally, the action of efgartigimod is
selective, with transient and incomplete reduction of IgG
and no effect on other immunoglobulins. Preclinical
models have also shown that IgG production is not
impaired.33 Because of these factors, efgartigimod-treated
patients should retain the potential to mount an IgG
immune response.
Strengths of this study include the randomised placebo-
controlled design, using validated scales incorporating
physician and patient assessment, and endpoints requir­
ing a combination of clinically meaningful improve­ment
and sustained effect. The prolonged response requirement
aimed to reduce the placebo effect and more reliably
ascertain the treatment effect of efgartigimod. A broad
population of patients with generalised myasthenia gravis
was recruited.
Study limitations included the length of follow-up,
which will be addressed by the ongoing open-label exten­
sion study. The retreatment criteria requiring patients’
MG-ADL score to return to less than a 2-point reduction
from baseline was a rigorous ADAPT study criterion and
the usefulness in the real world will be established in
clinical practice. The inclusion of acetylcholine receptor
antibody-negative patients was important due to the
limited treatment options these patients have and their
lack of inclusion in previous clinical trials. However, only
a few of these patients were recruited, and the trial
www.thelancet.com/neurology Vol 20 July 2021

was not statistically powered to assess efficacy in this
population.
The results of the phase 3 ADAPT trial suggest that the
novel mechanism of selective IgG reduction through
blocking of FcRn with efgartigimod is an effective and
well tolerated treatment for patients with generalised
myasthenia gravis.
Contributors
All authors had full access to the study design information and all data
in the study and had final responsibility for the decision to submit for
publication. JFH, VB, HM, AG, PU, TVa, JV, and RM contributed to the
concept or design of the study. All authors contributed to the analysis
and interpretation of data. JFH, AG, PU, and TVa accessed and verified
the data in the study. Cello Health Communications, a medical writing
company, produced the first draft of the paper based on input and
direction from all authors. All authors had full access to study data,
reviewed, edited, and provided final approval of the manuscript content,
and had final responsibility for the decision to submit for publication.
Declaration of interests
JFH has received research support from Alexion Pharmaceuticals,
argenx, the Centers for Disease Control and Prevention (Atlanta, GA,
USA), the Muscular Dystrophy Association, the National Institutes of
Health (NIH; including the National Institute of Neurological Disorders
and Stroke and the National Institute of Arthritis and Musculoskeletal
and Skin Diseases), Patient Centered Outcomes Research Institute,
and Ra Pharmaceuticals (now UCB); honoraria from Alexion
Pharmaceuticals, argenx, Immunovant, Ra Pharmaceuticals (now UCB),
Regeneron Pharmaceuticals, and Viela Bio; and non-financial support
from Alexion Pharmaceuticals, argenx, Ra Pharmaceuticals (now UCB),
and Toleranzia. VB has received research support from Commonwealth
Serum Laboratories, Grifols, UCB, Bionevia, Shire, and Octapharma.
TVu has served as a speaker for Alexion; has done consulting work for
argenx and UCB; and participated in trials in myasthenia gravis
sponsored by NIH, Alexion Pharmaceuticals, argenx, Ra, Viela Bio,
UCB, and Grifols. CK has served on advisory boards for Acceleron,
Akcea, Alexion, Alnylam, argenx, Biogen, CSL Behring, Cytokinetics,
and Sanofi-Genzyme; and received research grants from Genzyme and
Akcea. SP reports lecture honoraria from Pfizer, Teva Actavis, Berlin
Chemie Menarini, Mylan, Worwag, Adoc, and Salveo; research grants
from Kedrion, Octapharma, and Argenx; consultant fees from argenx,
Mylan, and Roche; and travel grants from Octapharma, Kedrion,
Teva Actavis, Sanofi Genzyme, Pfizer, Roche, Adoc, and Berlin Chemie
Menarini, all outside the submitted work. HM has served as a paid
consultant for Alexion Pharmaceuticals, argenx, and Ra Pharma;
and has received speaker honoraria from the Japan Blood Products
Organization and research support from the Ministry of Health, Labor,
and Welfare, Japan. AG, PU, and TVa are full-time employees of argenx,
Ghent, Belgium. KU has served as a paid consultant for argenx,
Ra Pharma, UCB Pharma, Viela Bio, and Regeneron Pharmaceuticals;
and has received speaker honoraria from Alexion Pharmaceuticals and
the Japan Blood Products Organization. JV receives research support
from Target to B consortium, Prinses Beatrix Spierfonds, and argenx;
has been involved in trials or consultancies for argenx, Alexion,
and Ra pharma; JV is coinventor on patent applications based on
MUSK-related research; and is a member of the European Reference
Network for Rare Neuromuscular Diseases; and JV’s institution received
royalties from Immuno-Biological Laboratories. RM has received
personal compensation for consulting, serving on a scientific advisory
board, speaking, or other activities with BioMarin, Catalyst, Alexion
Pharmaceuticals, UCB, and argenx. All other authors declare no
competing interests.
Data sharing
argenx is committed to responsible data sharing regarding the clinical
trials they fund. Included in this commitment is access to anonymised,
individual, and trial-level data (analysis datasets), and other information
(eg, protocols and clinical study reports), as long as the trials are not part
of an ongoing or planned regulatory submission. This includes requests
for clinical trial data for unlicensed products and indications. These
www.thelancet.com/neurology Vol 20 July 2021
Articles
clinical trial data can be requested by qualified researchers who engage
in rigorous independent scientific research and will only be provided
after review and approval of a research proposal and statistical analysis
plan and execution of a data sharing agreement. Data requests can be
submitted at any time and the data will be accessible for 12 months.
Requests can be submitted to ESR@argenx.com.
Acknowledgments
We thank all the study participants, investigators, and trial teams for
their participation in the trial. We would also like to acknowledge the
support provided by Benjamin Van Hoorick, Patricia Crabbe,
and Caroline T’joen. Medical writing assistance was provided by Cello
Health Communications (funded by argenx) and Brant Hubbard
(argenx). The ADAPT study was sponsored by argenx.
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 1

Table of Contents

Table 1. List of Study Investigators and Sites……………………………………...pages 2 - 11

Table 2. Inclusion and Exclusion Criteria……………………………………...…pages 11 - 12

Table 3. Number of cycles received by all patients……………………………………..page 13

Figure 1. Change in antibody levels…………………………………………………….page 14

Table 4. ADAPT Investigator Study Group…………………………………………….page 15

1
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Supplemental Table 1. List of Investigators and Sites

Investigator Site Country

AZ Sint-Lucas & Volkskliniek, Campus Sint-Lucas,
Jan De Bleecker Belgium
Neurology
AZ Sint-Lucas & Volkskliniek, Campus Sint-Lucas,
Belgium
Kathy De Koning Neurology
AZ Sint-Lucas & Volkskliniek, Campus Sint-Lucas,
Belgium
Katrien De Mey Neurology
AZ Sint-Lucas & Volkskliniek, Campus Sint-Lucas,
Belgium
Annelien De Pue Neurology
Rudolf Mercelis Antwerp University Hospital, Department of Neurology Belgium

Antwerp University Hospital, Department of Neurology Belgium

Maren Wyckmans
Antwerp University Hospital, Department of Neurology Belgium
Caroline Vinck
Antwerp University Hospital, Department of Neurology Belgium
Linda Wagemaekers
Antwerp University Hospital, Department of Neurology Belgium
Jonathan Baets
Vera Bril Toronto General Hospital, University Health Network Canada

Toronto General Hospital, University Health Network Canada

Eduardo Ng
Toronto General Hospital, University Health Network Canada
Jafar Shabanpour
Toronto General Hospital, University Health Network Canada
Lubna Daniyal
Toronto General Hospital, University Health Network Canada
Shabber Mannan
Toronto General Hospital, University Health Network Canada
Hans Katzberg
Angela Genge Montreal Neurological Institute & Hospital Canada

Zaeem Siddiqi University of Alberta Hospital Canada

Czech
Jana Junkerová Neurology Clinic, Faculty Hospital Ostrava
Republic
Czech
Neurology Clinic, Faculty Hospital Ostrava
Jana Horakova Republic
Czech
Neurology Clinic, Faculty Hospital Ostrava
Katerina Reguliova Republic
General Faculty Hospital Prague, Neurology Clinic - Czech
Michaela Tyblova
Centre for Myastenia Gravis Republic

2
 3

General Faculty Hospital Prague, Neurology Clinic - Czech

Ivana Jurajdova Centre for Myastenia Gravis Republic
General Faculty Hospital Prague, Neurology Clinic - Czech
Iveta Novakova Centre for Myastenia Gravis Republic
General Faculty Hospital Prague, Neurology Clinic - Czech
Michala Jakubikova Centre for Myastenia Gravis Republic
General Faculty Hospital Prague, Neurology Clinic - Czech
Jiri Pitha Centre for Myastenia Gravis Republic
Czech
Stanislav Vohanka Fakultní nemocnice Brno
Republic
Czech
Fakultní nemocnice Brno
Katerina Havelkova Republic
Czech
Fakultní nemocnice Brno
Tomas Horak Republic
Czech
Fakultní nemocnice Brno
Josef Bednarik Republic
Czech
Fakultní nemocnice Brno
Mageda Horakova Republic
Charité - Universitätsmedizin Berlin, Department of
Andreas Meisel Germany
Neurology, NeuroCure Clinical Research Center
Charité - Universitätsmedizin Berlin, Department of
Germany
Dike Remstedt Neurology, NeuroCure Clinical Research Center
Charité - Universitätsmedizin Berlin, Department of
Germany
Claudia Heibutzki Neurology, NeuroCure Clinical Research Center
Charité - Universitätsmedizin Berlin, Department of
Germany
Siegfried Kohler Neurology, NeuroCure Clinical Research Center
Charité - Universitätsmedizin Berlin, Department of
Germany
Sarah Hoffman Neurology, NeuroCure Clinical Research Center
Charité - Universitätsmedizin Berlin, Department of
Germany
Frauke Stascheit Neurology, NeuroCure Clinical Research Center
Copenhagen Neuromuscular Center, 8077,
John Vissing Denmark
Rigshospitalet, Universitu of Copenhagen
Copenhagen Neuromuscular Center, 8077,
Denmark
Lizzie Zafirakos Rigshospitalet, Universitu of Copenhagen
Copenhagen Neuromuscular Center, 8077,
Denmark
Kuldeep Kumar Khatri Rigshospitalet, Universitu of Copenhagen
Copenhagen Neuromuscular Center, 8077,
Denmark
Anne Autzen Rigshospitalet, Universitu of Copenhagen
Mads Peter Godtfeldt Copenhagen Neuromuscular Center, 8077,
Denmark
Stemmerik Rigshospitalet, Universitu of Copenhagen

Henning Andersen Aarhus University Hospital Denmark

Hôpital de la Timone, Service de Neurologie et
Shahram Attarian France
Maladies Neuromusculaires
Temur Margania Ltd. "New Hospitals", Department of Neurology Georgia

3
 4

Roman Sakarishvili Ltd Petre Sarajishvili Institute of Neurology Georgia

Pineo Medical Ecosystem Ltd., Department of

Alexander Tsiskaridze Georgia
Neurology Service
Jahn Ferenc Dél-pesti Kórház és Rendelőintézet,
Csilla Rózsa Hungaray
Neurológiai Osztály,
Jahn Ferenc Dél-pesti Kórház és Rendelőintézet,
Hungaray
Gedeonne Margo Jakab Neurológiai Osztály,
Jahn Ferenc Dél-pesti Kórház és Rendelőintézet,
Hungaray
Szilvia Toth Neurológiai Osztály,
Jahn Ferenc Dél-pesti Kórház és Rendelőintézet,
Hungaray
Gyorgyi Szabo Neurológiai Osztály,
Jahn Ferenc Dél-pesti Kórház és Rendelőintézet,
Hungaray
David Bors Neurológiai Osztály,
Jahn Ferenc Dél-pesti Kórház és Rendelőintézet,
Hungaray
Eniko Szabo Neurológiai Osztály,
lstituto Neurologico Carlo Besta, I.R.C.C.S U.O.
Renato Mantegazza Italy
Neuroimmunologia e malattie neuromuscolari
lstituto Neurologico Carlo Besta, I.R.C.C.S U.O.
Italy
Angela Campanella Neuroimmunologia e malattie neuromuscolari
lstituto Neurologico Carlo Besta, I.R.C.C.S U.O.
Italy
Fiammetta Vanoli Neuroimmunologia e malattie neuromuscolari
lstituto Neurologico Carlo Besta, I.R.C.C.S U.O.
Italy
Rita Frangiamore Neuroimmunologia e malattie neuromuscolari
lstituto Neurologico Carlo Besta, I.R.C.C.S U.O.
Italy
Carlo Antozzi Neuroimmunologia e malattie neuromuscolari
lstituto Neurologico Carlo Besta, I.R.C.C.S U.O.
Italy
Silvia Bonanno Neuroimmunologia e malattie neuromuscolari
lstituto Neurologico Carlo Besta, I.R.C.C.S U.O.
Italy
Lorenzo Maggi Neuroimmunologia e malattie neuromuscolari
lstituto Neurologico Carlo Besta, I.R.C.C.S U.O.
Italy
Riccardo Giossi Neuroimmunologia e malattie neuromuscolari
Azienda Ospedaliera Universitaria FEDERICO II,
Francesco Saccà Dipartimento di Neuroscienze, Scienze Riproduttive E Italy
Odontostomatologia
Azienda Ospedaliera Universitaria FEDERICO II,
Dipartimento di Neuroscienze, Scienze Riproduttive E Italy
Angela Marsili Odontostomatologia
Azienda Ospedaliera Universitaria FEDERICO II,
Dipartimento di Neuroscienze, Scienze Riproduttive E Italy
Tiziana Imbriglio Odontostomatologia
Neurology Unit, Sant'Andrea Hospital-University of
Giovanni Antonini Italy
Rome La Sapienza
Neurology Unit, Sant'Andrea Hospital-University of
Girolamo Alfieri Italy
Rome La Sapienza
Neurology Unit, Sant'Andrea Hospital-University of
Italy
Stefania Morino Rome La Sapienza

4
 5

Neurology Unit, Sant'Andrea Hospital-University of

Italy
Matteo Garibaldi Rome La Sapienza
Neurology Unit, Sant'Andrea Hospital-University of
Italy
Laura Fionda Rome La Sapienza
Neurology Unit, Sant'Andrea Hospital-University of
Italy
Luca Leonardi Rome La Sapienza
Toho University Hospital Ohashi Medical Center,
Shingo Konno Japan
Department of Neurology
Akiyuki Uzawa Chiba University Hospital, Department of Neurology Japan

Chiba University Hospital, Department of Neurology Japan

Kaoru Sakuma
Chiba University Hospital, Department of Neurology Japan
Chiho Watanabe
Chiba University Hospital, Department of Neurology Japan
Yukiko Ozawa
Chiba University Hospital, Department of Neurology Japan
Manato Yasuda
Chiba University Hospital, Department of Neurology Japan
Yosuke Onishi
Makoto Samukawa Kindai University Hospital, Department of Neurology Japan

Kimiaki Utsugisawa General Hanamaki Hospital Japan

Tomoko Tsuda
General Hanamaki Hospital Japan

Yasushi Suzuki Sendai Medical Center, Department of Neurology Japan

Sendai Medical Center, Department of Neurology Japan

Sayaka Ishida
Sendai Medical Center, Department of Neurology Japan
Genya Watanabe
International University of Health and Welfare, Mita
Hiroyuki Murai Japan
Hospital, Department of Neurology

Masanori Takahashi Osaka University Hospital, Department of Neurology Japan

Osaka University Hospital, Department of Neurology Japan

Hiroko Nakamura
Osaka University Hospital, Department of Neurology Japan
Erina Sugano
Osaka University Hospital, Department of Neurology Japan
Tomoya Kubota
Sapporo Medical University Hospital, Division of
Tomihiro Imai Japan
Neurology
Sapporo Medical University Hospital, Division of
Japan
Mari Suzuki. Neurology

5
 6

Sapporo Medical University Hospital, Division of

Japan
Ayako Mori Neurology
Sapporo Medical University Hospital, Division of
Japan
Daisuke Yamamoto Neurology
Sapporo Medical University Hospital, Division of
Japan
Kazuna Ikeda Neurology
Sapporo Medical University Hospital, Division of
Japan
Shin Hisahara Neurology
Tokyo Medical University Hospital, Department of
Masayuki Masuda Japan
Neurology
Tokyo Medical University Hospital, Department of
Japan
Miki Takaki Neurology
Tokyo Medical University Hospital, Department of
Japan
Kanako Minemoto Neurology
Tokyo Medical University Hospital, Department of
Japan
Nobuhiro Ido Neurology
Tokyo Medical University Hospital, Department of
Japan
Makiko Naito Neurology
Tokyo Medical University Hospital, Department of
Japan
Yoshihiko Okubo Neurology

Takamichi Sugimoto Hiroshima City Hiroshima Citizens Hospital Japan

Hiroshima City Hiroshima Citizens Hospital Japan

Yuka Takematsu
Hiroshima City Hiroshima Citizens Hospital Japan
Ayumi Kamei
Hiroshima City Hiroshima Citizens Hospital Japan
Mihiro Shimizu
Hiroshima City Hiroshima Citizens Hospital Japan
Hiroyuki Naito
Hiroshima City Hiroshima Citizens Hospital Japan
Eiichi Nomura
Johannes Verschuuren Leids Universitair Medisch Centrum (LUMC) Netherlands

Leids Universitair Medisch Centrum (LUMC) Netherlands

Marjolein Van Heur
Leids Universitair Medisch Centrum (LUMC) Netherlands
Anne-Marie Peters
Leids Universitair Medisch Centrum (LUMC) Netherlands
Martijn Tannemaat
Leids Universitair Medisch Centrum (LUMC) Netherlands
Annabel Ruiter
Leids Universitair Medisch Centrum (LUMC) Netherlands
Kevin Keene
University Clinical Center, Department of Adult
Malgorzata Bilinska Poland
Neurology

6
 7

Marek Halas University Clinical Center, Department of Adult

Poland
Neurology
Krakow Academy of Neurology, Center of Clinical
Andrzej Szczudlik Poland
Neurology
Krakow Academy of Neurology, Center of Clinical
Poland
Marta Pinkosz Neurology
Krakow Academy of Neurology, Center of Clinical
Poland
Monika Frasinska Neurology
Krakow Academy of Neurology, Center of Clinical
Poland
Grazyna Zwolinska Neurology
Independent Public Central Hospital in Warsaw,
Anna Kostera-Pruszczyk Poland
Neurology Clinic
Independent Public Central Hospital in Warsaw,
Poland
Aleksandra Golenia Neurology Clinic
Independent Public Central Hospital in Warsaw,
Poland
Piotr Szczudlik Neurology Clinic
NZOZ Wielospecjalistyczna Poradnia Lekarska
Lech Szczechowski Poland
"Synapsis"
Ewelina Marek NZOZ Wielospecjalistyczna Poradnia Lekarska
Poland
"Synapsis"
Samara Regional Clinical Hospital, Department of
Irina Poverennova Russia
Neurosurgery
Samara Regional Clinical Hospital, Department of
Russia
Lubov Urtaeva Neurosurgery
Samara Regional Clinical Hospital, Department of
Russia
Nadezhda Kuznetsova Neurosurgery
Samara Regional Clinical Hospital, Department of
Russia
Tatiana Romanova Neurosurgery
Novosibirsk Regional Hospital, Regional Center of
Malkova Nadezhda Multiple Sclerosis and other Autoimmune Disorders of Russia
Nervous System
Novosibirsk Regional Hospital, Regional Center of
Multiple Sclerosis and other Autoimmune Disorders of Russia
Elena Lapochka Nervous System
Novosibirsk Regional Hospital, Regional Center of
Multiple Sclerosis and other Autoimmune Disorders of Russia
Denis Korobko Nervous System
Novosibirsk Regional Hospital, Regional Center of
Multiple Sclerosis and other Autoimmune Disorders of Russia
Ilona Vergunova Nervous System
Novosibirsk Regional Hospital, Regional Center of
Multiple Sclerosis and other Autoimmune Disorders of Russia
Anna Melnikova Nervous System
Novosibirsk Regional Hospital, Regional Center of
Multiple Sclerosis and other Autoimmune Disorders of Russia
Ekaterina Bulatova Nervous System
Nizhegorodsky Regional Clinical Hospital named after
Elena Antipenko Russia
NA Semashko

7
 8

Stojan Peric Clinical Center of Serbia, Clinic for Neurology Serbia

Clinical Center of Serbia, Clinic for Neurology Serbia

Ivo Bozovic
Clinical Center of Serbia, Clinic for Neurology Serbia
Dragana Lavrnic
Clinical Center of Serbia, Clinic for Neurology Serbia
Vidosava Rakocevic Stojanovic
University of Southern California, Healthcare United
Said Beydoun
Consultation Center II States
University of Southern California, Healthcare United
Salma Akhter Consultation Center II States
University of Southern California, Healthcare United
Ali Malekniazi Consultation Center II States
University of Southern California, Healthcare United
Leila Darki Consultation Center II States
University of Southern California, Healthcare United
Norianne Pimentel Consultation Center II States
University of Southern California, Healthcare United
Victoria Cannon Consultation Center II States
United
James F. Howard Jr. The University of North Carolina
States
United
The University of North Carolina
Manisha Chopra States
United
The University of North Carolina
Rebecca Traub States
UCI ALS & Neuromuscular Center, Neuromuscular United
Tahseen Mozaffar
Clinical Trials Unit States
UCI ALS & Neuromuscular Center, Neuromuscular United
Ivonne Turner Clinical Trials Unit States
UCI ALS & Neuromuscular Center, Neuromuscular United
Ali Habib Clinical Trials Unit States
UCI ALS & Neuromuscular Center, Neuromuscular United
Namita Goyal Clinical Trials Unit States
UCI ALS & Neuromuscular Center, Neuromuscular United
Manisha Kak Clinical Trials Unit States
United
Tuan Vu University of South Florida
States
United
University of South Florida
Erik Velasquez States
United
University of South Florida
Lucy Lam States
United
University of South Florida
Niraja Suresh States
United
University of South Florida
Jerrica Farias States

8
 9

United
Sarah Jones University of Virginia Health System
States
United
University of Virginia Health System
Mary Wagoner States
United
University of Virginia Health System
Debbie Eggleston States
United
Tulio Bertorini Wesley Neurology Clinic
States
United
Wesley Neurology Clinic
Cindy Benzel States
United
Wesley Neurology Clinic
Robert Henegar States
United
Wesley Neurology Clinic
Rekha Pillai States
University of Texas Health Science Center at San United
Ratna Bharavaju-Sanka
Antonio States
University of Texas Health Science Center at San United
Carolyn Paiz Antonio States
University of Texas Health Science Center at San United
Carlayne Jackson Antonio States
Medical University of South Carolina, Department of United
Katherine Ruzhansky
Neurology States
United
Chafic Karam Oregon Health & Science University
States
United
Oregon Health & Science University
Diana Dimitrova States
United
Oregon Health & Science University
Amy Visser States
United
Oregon Health & Science University
Nizar Chahin States
United
Todd Levine HonorHealth Neurology, 3501 N. Scottsdale Road
States
United
Robert Lisak Wayne State University, Department of Neurology
States
United
Wayne State University, Department of Neurology
Kelly Jia States
United
Wayne State University, Department of Neurology
Flicia Mada States
United
Wayne State University, Department of Neurology
Evanthia Bernitsas States
University of Kansas Medical Center, Department of United
Mamatha Pasnoor
Neuromuscular Research States
University of Kansas Medical Center, Department of United
Katherine Roath Neuromuscular Research States
University of Kansas Medical Center, Department of United
Samantha Colgan Neuromuscular Research States

9
 10

University of Kansas Medical Center, Department of United

Melissa Currence Neuromuscular Research States
University of Kansas Medical Center, Department of United
Andrew Heim Neuromuscular Research States
University of Kansas Medical Center, Department of United
Richard Barohn Neuromuscular Research States
University of Kansas Medical Center, Department of United
Mazen Dimachkie Neuromuscular Research States
University of Kansas Medical Center, Department of United
Jeffrey Statland Neuromuscular Research States
University of Kansas Medical Center, Department of United
Omar Jawdat Neuromuscular Research States
University of Kansas Medical Center, Department of United
Duaa Jabari Neuromuscular Research States
University of Kansas Medical Center, Department of United
Constantine Farmakidis Neuromuscular Research States
Southern Illinois University School of Medicine, United
James Gilchrist
Department of Neurology States
United
Yuebing Li Cleveland Clinic Foundation, Neuromuscular Center
States
United
Cleveland Clinic Foundation, Neuromuscular Center
Irys Caristo States
United
Cleveland Clinic Foundation, Neuromuscular Center
Debbie Hastings States
United
Cleveland Clinic Foundation, Neuromuscular Center
John Anthony Morren States
United
Michael Weiss University of Washington, Department of Neurology
States
United
Srikanth Muppidi Stanford Neuromuscular Research
States
United
Stanford Neuromuscular Research
Tia Nguyen States
United
Stanford Neuromuscular Research
Lesly Welsh States
United
Stanford Neuromuscular Research
Yuen So States
United
Stanford Neuromuscular Research
Neelam Goyal States
United
Michael Pulley University of Florida Health Science Center Jacksonville
States
United
University of Florida Health Science Center Jacksonville
Cathy Bailey States
United
University of Florida Health Science Center Jacksonville
Lisa Smith States
United
University of Florida Health Science Center Jacksonville
Alan Berger States

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North County Neurology Associates, Research United

Gregory Sahagian
Department States
North County Neurology Associates, Research United
Yasmin Camberos Department States
North County Neurology Associates, Research United
Benjamin Frishberg Department States

Table 2. Inclusion and Exclusion Criteria.

Inclusions Criteria
• Patients with the ability to understand the requirements of the trial, provide written
informed consent, and comply with the trial protocol procedures.
• Adult patients with gMG.
• All serotypes, regardless of Ab status and including MuSK, LRP4, and AChR-Ab- in
addition to AChR-Ab+.
• MGFA Class II-IV gMG. The confirmation of the diagnosis should be documented
and supported by ≥1 of the following 3 tests:
• MGFA Class II-IV gMG. The confirmation of the diagnosis should be documented
and supported by ≥1 of the following 3 tests:
o History of abnormal neuromuscular transmission demonstrated by single-fiber
electromyography or repetitive nerve stimulation
o History of positive edrophonium chloride test
o Patient has demonstrated improvement in MG signs on oral
acetylcholinesterase inhibitors as assessed by the treating physician
• MG-ADL score ≥5, with ≥50% of the total score due to non-ocular symptoms
• Receiving a stable dose of ≥1 of the following gMG treatments prior to randomization:
acetylcholinesterase inhibitors (no dose change for 2 weeks prior to screening),
steroids (at least 3 months of treatment, no dose change for 1 month) or NSIST (at
least 6 months of treatment, no dose change for 3 months)

Exclusion Criteria:
• Have been treated with IVIg/plasma exchange in the past month, with rituximab or
eculizumab in the past 6 months, with an investigational drug within 3 months or 5
half-lives of the drug (whichever is longer) prior to screening, or had a thymectomy in
the past 3 months or a planned thymectomy during the trial period.
• MGFA Class I and V patients
• Have hepatitis B or C, HIV, severe infections, or malignancies
• Have low IgG serum levels (<6 g/L)
• Female patients who are pregnant or lactating, or are intending to become pregnant
• Male patients who are sexually active and do not intend to use effective methods of
contraception during the trial or within 90 days after the last dosing or male patients
who plan to donate sperm during the trial or within 90 days after the last dosing
• History of any known bacterial, viral, or fungal infection or any major episode of
infection that required hospitalization or injectable antimicrobial therapy in the last 8
weeks prior to screening
• History of autoimmune disease other than MG (e.g. thyroiditis, rheumatoid arthritis,
etc.) that would interfere with an accurate assessment of clinical symptoms
• Documented lack of clinical response to PLEX

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• Patients who previously participated in a clinical trial with efgartigimod

• Patients who received a vaccination (e.g., influenza vaccine) within the last 4 weeks
prior to screening
• Patients with clinical evidence of other significant serious disease or patients who
underwent a recent major surgery, which could confound the results of the trial or put
the patient at undue risk. Patients with renal/hepatic function impairment could be
included
• Patients who have a history of malignancy, including malignant thymoma, or
myeloproliferative or lymphoproliferative disorders, unless deemed cured by adequate
treatment with no evidence of recurrence for ≥3 years before screening. Patients with
completely excised non-melanoma skin cancer (such as basal cell carcinoma or
squamous cell carcinoma) or cervical carcinoma in situ would be permitted at any time
• Patients with worsening muscle weakness secondary to concurrent infections or
medications (aminoglycosides, fluoroquinolones, beta-blockers, etc.)
AChR-Ab+, acetylcholine receptor autoantibody positive; gMG, generalized myasthenia gravis; HIV, human
immunodeficiency virus; IgG, immunoglobulin G; IVIg, intravenous immunoglobulin G; LRP4, lipoprotein
receptor-related protein-4; MG, myasthenia gravis; MG-ADL, Myasthenia Gravis Activities of Daily Living;
MuSK, muscle-specific kinase; NSIT, non-steroidal immunosuppressive therapy; PLEX, plasma exchange

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Table 2: Number of cycles received by all patients

Efgartigimod (n=84) Placebo (n=83)

Maximum Patients, n (%) Discontinued Patients, n (%) Discontinued

number of treatment during treatment during

cycles cycle cycle

1 21 (25%) 4 26 (31⸱3%) 9

2 56 (66⸱7%) 1 54 (65⸱1%) 1

3 7 (8⸱3%) 0 3 (3⸱6%) 0

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Figure 4

Figure 1: Change in antibody levels: Mean change over time in C1 of IgG and AChR-Ab
levels in AChR-Ab+ patients.

14
 15

Table 4. ADAPT Investigator Study Group

Jan De Bleeker

Kathy De Koning

Katrien De Mey

Annelien De Pue

Rudolf Mercelis

Maren Wyckmans

Caroline Vinck

Linda Wagemaekers

Jonathan Baets

Eduardo Ng

Jafar Shabanpour

Lubna Daniyal

Shabber Mannan

Hans Katzberg

Angela Genge

Zaeem Siddiqi

Jana Junkerová

Jana Horakova

Katerina Reguliova

Michaela Tyblova

Ivana Jurajdova

Iveta Novakova

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 16

Michala Jakubikova

Jiri Pitha

Stanislav Vohanka

Katerina Havelkova

Tomas Horak

Josef Bednarik

Mageda Horakova

Andreas Meisel

Dike Remstedt

Claudia Heibutzki

Siegfried Kohler

Sarah Hoffman

Frauke Stascheit

John Vissing

Lizzie Zafirakos

Kuldeep Kumar Khatri

Anne Autzen

Mads Peter Godtfeldt Stemmerik

Henning Andersen

Shahram Attarian

Alexander Tsiskaridze

Csilla Rózsa

Gedeonne Margo Jakab

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 17

Szilvia Toth

Gyorgyi Szabo

David Bors

Eniko Szabo

Angela Campanella

Fiammetta Vanoli

Rita Frangiamore

Carlo Antozzi

Silvia Bonanno

Lorenzo Maggi

Riccardo Giossi

Francesco Saccà

Angela Marsili

Tiziana Imbriglio

Giovanni Antonini

Girolamo Alfieri

Stefania Morino

Matteo Garibaldi

Laura Fionda

Luca Leonardi

Shingo Konno

Akiyuki Uzawa

Kaoru Sakuma

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 18

Chiho Watanabe

Yukiko Ozawa

Manato Yasuda

Yosuke Onishi

Makoto Samukawa

Tomoko Tsuda

Yasushi Suzuki

Sayaka Ishida

Genya Watanabe

Masanori Takahashi

Hiroko Nakamura

Erina Sugano

Tomoya Kubota

Tomihiro Imai

Mari Suzuki.

Ayako Mori

Daisuke Yamamoto

Kazuna Ikeda

Shin Hisahara

Masayuki Masuda

Miki Takaki

Kanako Minemoto

Nobuhiro Ido

18
 19

Makiko Naito

Yoshihiko Okubo

Takamichi Sugimoto

Yuka Takematsu

Ayumi Kamei

Mihiro Shimizu

Hiroyuki Naito

Eiichi Nomura

Marjolein Van Heur

Anne-Marie Peters

Martijn Tannemaat

Annabel Ruiter

Kevin Keene

Marek Halas

Andrzej Szczudlik

Marta Pinkosz

Monika Frasinska

Grazyna Zwolinska

Anna Kostera-Pruszczyk

Aleksandra Golenia

Piotr Szczudlik

Lech Szczechowski

Ewelina Marek

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 20

Irina Poverennova

Lubov Urtaeva

Nadezhda Kuznetsova

Tatiana Romanova

Malkova Nadezhda

Elena Lapochka

Denis Korobko

Ilona Vergunova

Anna Melnikova

Ekaterina Bulatova

Elena Antipenko

Ivo Bozovic

Dragana Lavrnic

Vidosava Rakocevic Stojanovic

Said Beydoun

Salma Akhter

Ali Malekniazi

Leila Darki

Norianne Pimentel

Victoria Cannon

Manisha Chopra

Rebecca Traub

Tahseen Mozaffar

20
 21

Ivonne Turner

Ali Habib

Namita Goyal

Manisha Kak

Erik Velasquez

Lucy Lam

Niraja Suresh

Jerrica Farias

Sarah Jones

Mary Wagoner

Debbie Eggleston

Tulio Bertorini

Cindy Benzel

Robert Henegar

Rekha Pillai

Ratna Bharavaju-Sanka

Carolyn Paiz

Carlayne Jackson

Katherine Ruzhansky

Diana Dimitrova

Amy Visser

Nizar Chahin

Todd Levine

21
 22

Robert Lisak

Kelly Jia

Flicia Mada

Evanthia Bernitsas

Mamatha Pasnoor

Katherine Roath

Samantha Colgan

Melissa Currence

Andrew Heim

Richard Barohn

Mazen Dimachkie

Jeffrey Statland

Omar Jawdat

Duaa Jabari

Constantine Farmakidis

James Gilchrist

Yuebing Li

Irys Caristo

Debbie Hastings

John Anthony Morren

Michael Weiss

Srikanth Muppidi

Tia Nguyen

22
 23

Lesly Welsh

Yuen So

Neelam Goyal

Michael Pulley

Cathy Bailey

Lisa Smith

Alan Berger

Gregory Sahagian

Yasmin Camberos

Benjamin Frishberg

23