Zeitschrift für

Rheumatologie
Originalien
Z Rheumatol
https://doi.org/10.1007/s00393-022-01315-0
Accepted: 12 December 2022
Comparison of the efficacy and
© The Author(s), under exclusive licence to safety of tocilizumab, sarilumab,
Springer Medizin Verlag GmbH, ein Teil von
Springer Nature 2023 and olokizumab in patients with
Redaktion
Ulf Müller-Ladner, Bad Nauheim
Uwe Lange, Bad Nauheim
active rheumatoid arthritis:
a network meta-analysis of
randomized controlled trials
Young Ho Lee1,2 · Gwan Gyu Song1
1
Department of Rheumatology, Korea University College of Medicine, Seoul, Korea (Republic of)
2
Division of Rheumatology, Department of Internal Medicine, Korea University Anam Hospital, Korea
University College of Medicine, Seongbuk-gu, Korea (Republic of)

Abstract

Objective: This study compared the relative efficacy and safety of olokizumab,
tocilizumab, and sarilumab in rheumatoid arthritis (RA) patients who were intolerant
or responding inadequately to methotrexate (MTX).
Methods: We performed a Bayesian network meta-analysis to combine direct and
indirect evidence from randomized controlled trials (RCTs) to examine the efficacy and
safety of olokizumab, tocilizumab, and sarilumab in RA patients who were intolerant or
responding inadequately to MTX.
Results: Six RCTs comprising 4439 patients met the inclusion criteria. Tocilizumab,
sarilumab, olokizumab, and adalimumab treatments achieved a significant American
College of Rheumatology 20% (ACR20) response rate compared with placebo. However,
tocilizumab was associated with the most favorable surface area using the cumulative
ranking curve (SUCRA) for the ACR20 response rate. The ranking probability based
on the SUCRA indicated that tocilizumab treatment had the highest probability of
providing the best ACR20 response rate, followed by sarilumab, olokizumab every
2 weeks (Q2W), olokizumab Q4W, adalimumab 40 mg, and placebo. The ACR50 and 70
response rates showed a distribution pattern similar to that of the ACR20 response rate.
However, olokizumab Q4W had a higher ranking probability than olokizumab Q2W.
The SUCRA rating showed that the placebo was the best intervention with the least
adverse events (AEs) and withdrawal due to AEs, followed by interleukin-6 inhibitors.
Conclusion: Tocilizumab, sarilumab, and olokizumab are more effective than
adalimumab and have similar efficacy and safety in RA patients with inadequate
responses to MTX.

Keywords
Tocilizumab · Sarilumab · Olokizumab · Rheumatoid arthritis · Network meta-analysis

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Zeitschrift für Rheumatologie 1

Originalien
Table 1 Characteristics of the individual studies included in the network meta-analysis
Study Subjects Total Drugs No. of No. No. No. No. of seri- No. of withl
number patients achieving achieving achieving ous adverse drawal due to
ACR20 ACR50 ACR70 events adverse events
A. Olokizumab
Smolen MTX-IRa 1648 Olokizumab Q2W 464 344 234 133 324 21
2022 [30] Olokizumab Q4W 479 342 240 129 338 30
Adalimumab 462 319 214 119 302 26
Placebo 243 113 55 27 154 9
Nasonov MTX-IRa 428 Olokizumab Q2W 143 98 61 28 83 7
2022 [24] Olokizumab Q4W 142 101 69 32 81 5
Placebo 143 49 11 3 62 1
B. Tocilizumab
Yazici 2012 DMARD-IR 614 Tocilizumab 409 184 123 65 290 27
[35] Placebo 205 52 23 4 122 8
Nishimoto MTX-IRa 125 Tocilizumab 61 49 30 18 37 2
2009 [25] Placebo 64 16 7 4 17 3
Smolen MTX-IRa 409 Tocilizumab 205 120 90 45 143 16
2008 [29] Placebo 204 54 22 4 129 13
Genovese DMARD-IR 1216 Tocilizumab 803 488 302 165 584 31
2008 [12] Placebo 413 101 37 12 253 8
C. Sarilumab
Bumester MTX-IR 597 Sarilumab 200 mg 184 132 84 43 9 11
2016 [4] Adalimumab 185 108 55 22 12 13
Placebob 398a 133 68 28 23 20
Fleischmann TNF 365 Sarilumab 200 mg 184 265 75 100 48 17
2016 [9] blocker-IR Placebo 181 133 33 28 23 8
Genovese MTX-IR 797 Sarilumab 200 mg 399 112 184 30 10 59
2015 [11] Placebo 398 61 68 13 6 20
Huizinga MTX-IR 104 Sarilumab 200 mg 52 34 21 9 0 4
2014 [15] Placebo 52 24 8 1 2 2
ACR20, 50, 70 American College of Rheumatology 20%, 50%, or 70% response rate, MTX methotrexate, IR incomplete response, Q2W Every 2 weeks,
Q4W Every 4 weeks, DMARD disease-modifying anti-rheumatic drug
a
An inadequate response to MTX or intolerant to or inappropriate for MTX. All patients received conventional synthetic DMARD(s)
b
For network meta-analysis, data of placebo plus MTX was included from the study by Genovese et al. [11]

Table 2 Study numbers of biological

agents Introduction Notably, interleukin-6 (IL-6) is over-
Treatment Study Number of expressed in RA-affected tissues [26].
number patients Rheumatoid arthritis (RA) is a systemic Elevated IL-6 levels in the blood and syn-
Placebo 11 2381 autoimmune disease that causes persis- ovial fluid have been linked to synovitis,
Olokizumab Q2W 2 607 tent synovial joint inflammation, resulting systemic inflammation, bone metabolism,
Olokizumab Q4W 2 621 in disability and a poorer quality of life and joint deterioration [32]. Tocilizumab,
Tocilizumab 4 1478 [16, 18]. Conventional synthetic disease- a humanized anti-human IL-6 receptor
Adalimumab 2 647 modifying antirheumatic medications monoclonal antibody, is used to treat
Sarilumab 200 mg 5 899 (csDMARDs), such as methotrexate (MTX), individuals who have not responded to
are used to treat RA. Although MTX is tumor necrosis factor inhibitors or MTX.
Q2W every 2 weeks, Q4W every 4 weeks
a successful DMARD [8, 17], not all pa- It is used either alone or in combination
tients respond to this drug and 30% quit with MTX [29]. Sarilumab is a fully human,
treatment within a year of starting it, anti-IL-6 receptor α (IL-6Rα) monoclonal
often due to a lack of effectiveness or antibody that binds specifically to both
unacceptable side effects [2]. Patients soluble and membrane-bound IL-6 recep-
who do not respond to MTX are treated tors [10]. Olokizumab, a novel humanized
with biological DMARDs (bDMARDs). monoclonal antibody specific for IL-6, has
been developed to treat RA [9]. It binds

2 Zeitschrift für Rheumatologie

 Table 3 Network meta-analysis of the efficacy of all comparators along with odds ratios (upper number in each cell) and 95% credible interval (range)
A. ACR20. OR > 1 signifies that the treatment in the top left is better
Tocilizumab – – – – –
1.01 (0.77–1.32) Sarilumab 200 mg – – – –
1.16 (0.84–1.59) 1.15 (0.84–1.57) Olokizumab Q2W – – –
1.25 (0.91–1.71) 1.24 (0.91–1.68) 1.08 (0.84–1.39) Olokizumab Q4W – –
1.51 (1.12–2.02) 1.50 (1.13–1.97) 1.30 (1.01–1.68) 1.20 (0.94–1.55) Adalimumab –
4.12 (3.42–4.97) 4.09 (3.38–4.95) 3.55 (2.76–4.60) 3.29 (2.56–4.24) 2.74 (2.18–3.42) Placebo
B. ACR50
Tocilizumab – – – – –
1.24 (0.90–1.71) Sarilumab 200 mg – – – –
1.40 (0.97–2.01) 1.13 (0.82–1.55) Olokizumab Q4W – – –
1.46 (1.02–2.10) 1.18 (0.86–1.62) 1.04 (0.83–1.31) Olokizumab Q2W – –
1.89 (1.34–2.69) 1.53 (1.14–2.04) 1.36 (1.07–1.72) 1.30 (1.02–1.64) Adalimumab –
5.53 (4.34–7.13) 4.47 (3.64–5.51) 3.97 (3.04–5.17) 3.80 (2.91–4.95) 2.93 (2.29–3.72) Placebo
C. ACR70
Tocilizumab – – – – –
2.34 (1.45–3.82) Sarilumab 200 mg – – – –
3.03 (1.79–5.16) 1.29 (0.85–1.95) Olokizumab Q2W – – –
3.13 (1.85–5.29) 1.33 (0.88–2.02) 1.04 (0.80–1.33) Olokizumab Q4W – –
3.78 (2.26–6.32) 1.61 (1.10–2.36) 1.25 (0.95–1.65) 1.20 (0.92–1.59) Adalimumab –
10.16 (7.01–15.12) 4.34 (3.25–5.82) 3.36 (2.40–4.79) 3.25 (2.32–4.62) 2.70 (1.96–3.74) Placebo

to the IL-6 receptor site 3 and blocks the
interaction of IL-6 and IL-6 receptor dimer
with the signal-transducing β-receptor
subunit glycoprotein 130 of the receptor
complex [28]. Olokizumab was shown
to be considerably more effective than
placebo in clinical studies of RA [24, 30].
Olokizumab, similar to tocilizumab,
is an effective therapeutic drug in trials
of individuals with RA with an insuffi-
cient response to MTX. However, the
head-to-head effectiveness and safety of
tocilizumab, sarilumab, and olokizumab
has not been determined in these patients.
In the absence of direct comparison trials
of the relevant comparators [12, 24, 25,
29, 30, 35], information from random-
ized controlled trials (RCTs) of various
therapies must be combined to evaluate
the impact of different therapies. Using
a network meta-analysis, the current study
assessed the effectiveness and safety of
tocilizumab, sarilumab, and olokizumab
in patients with active RA and insufficient
response to MTX.
Methods
Identification of eligible studies and
data extraction
We searched for studies that examined
the efficacy and safety of olokizumab,
sarilumab, and tocilizumab in patients
with active RA who had an inadequate
response to MTX or were intolerant to
MTX. A literature search was performed
using MEDLINE, EMBASE, the Cochrane
Controlled Trials Register, and the Ameri-
can College of Rheumatology (ACR) and
the European League Against Rheuma-
tism (EULAR) conference proceedings to
identify available articles (up to Septem-
ber 2022). The following keywords and
subject terms were used: “olokizumab,”
“tocilizumab,” “sarilumab,” and “RA.” All
references cited in the studies were re-
viewed to identify additional reports
excluded from electronic databases. The
inclusion criteria for RCTs in the present
study were as follows: (1) the study
compared olokizumab, tocilizumab, or
sarilumab with a placebo to treat active
RA that inadequately responded to MTX;
(2) the study provided endpoints for the
clinical efficacy and safety of olokizumab,
tocilizumab, or sarilumab at 12–24 weeks;
(3) the study included patients diagnosed
with RA based on the ACR criteria for
RA [14] or the 2010 ACR/EULAR classifi-
cation criteria [1]. The exclusion criteria
were as follows: (1) studies that included
duplicate data and (2) studies that did
not contain adequate data for inclusion.
The primary endpoint for efficacy was the
number of patients who achieved an ACR
20% (ACR20) response rate as a preferred
outcome measure for testing efficacy.
The primary safety outcome crucial for
assessing risks was the number of patients
with serious adverse events (AEs). The
secondary endpoint for efficacy was the
number of patients who achieved an ACR
50% (ACR50) or 70% (ACR70) response
rate. Data were extracted from the original
studies by two independent reviewers.
The secondary endpoint for efficacy was
the number of patients who withdrew
owing to AEs. Any discrepancies between
reviewers were resolved by consensus.
The following information was extracted
from each study: first author; year of
publication; country of the study; doses
of IL-6 inhibitors and adalimumab; time
of outcome evaluation; and efficacy and
safety outcomes at 12–24 weeks. We
quantified the methodological qualities
of the three included studies using Jadad

Zeitschrift für Rheumatologie 3

Originalien
ond best, and so on, or into a ranking for
each treatment called the “surface under
the cumulative ranking curve” (SUCRA)
[27]. SUCRA is expressed as a percentage
(e.g., a value of 100% for SUCRA would be
obtained when a particular treatment is
guaranteed to be the best, and a value of
0% would guarantee that it is the worst
treatment). League tables were used to
organize summary estimates by ranking
treatments according to the strength of
their impact on the outcome based on
their respective SUCRA values [27]. We
reported the pairwise odds ratio (OR)
and 95% credible interval (CrI or Bayesian
CI) and adjusted them for multiple-arm
trials. Pooled results were considered
statistically significant when the span of
the 95% CrI did not include 1.

Test for inconsistency

Inconsistency is the disagreement be-
tween direct and indirect evidence [7].
Therefore, an assessment of inconsistency
is crucial when conducting a network
meta-analysis [13]. To assess the network
inconsistency between the direct and in-
direct estimates in each loop, we plotted
the posterior mean deviance of individual
data points in the inconsistency model
against their posterior mean deviance in
the consistency model [34].

Results

Studies included in the meta-

Fig. 1 8 Bayesian network meta-analysis of randomized controlled trials examining relative effec- analysis
tiveness according to the number of patients achieving the American College of Rheumatology 20%
response rate (ACR20) A total of 1005 studies were identified
through electronic or manual searches;
scores, with the quality classified as high the different arms were arranged based 33 were selected for a full-text review
(score of 3–5) or low (score of 0–2), and on the probability of the treatment to based on the title and abstract details.
conducted a network meta-analysis fol- be ranked as the best-performing regi- However, 23 studies were excluded be-
lowing the guidelines provided by the men. We adopted a Bayesian fixed-effects cause they were duplicates or irrelevant.
PRISMA statement [23]. model for network meta-analysis using Thus, 10 RCTs met the inclusion criteria [4,
NetMetaXL [3] and WinBUGS statistical 9, 11, 12, 15, 24, 25, 29, 30, 35]. The search
Evaluation of statistical associations analysis program, version 1.4.3 (MRC Bio- results contained ten pairwise compar-
for network meta-analysis statistics Unit, Institute of Public Health, isons, including seven direct comparisons,
Cambridge, UK). We used the Markov and five interventions. Various dosages of
The results from different arms were chain Monte Carlo method to obtain the the biologics were reported: olokizumab
analyzed simultaneously for RCTs that pooled effect sizes [5]. All chains were run at a dose of 64 mg was administered intra-
compared multiple doses of olokizumab, with 10,000 burn-in iterations followed by venously every 2 or 4 weeks (QW2, QW4);
tocilizumab, sarilumab, and placebo in 10,000 monitoring iterations. The relative tocilizumab at 8 mg/kg was administered
different arms. The efficacy and toler- effects were converted into a probability intravenously every 4 weeks; sarilumab
ability of the biologics and placebo in that a particular treatment was best, sec- 200 mg was administered subcutaneously

4 Zeitschrift für Rheumatologie

 every 2 weeks; and adalimumab 40 mg
was administered subcutaneously every
2 weeks. The Jadad scores of the studies
were between 3 and 5, indicating high-
quality studies (. Tables 1 and 2). The rel-
evant features of the studies included in
the meta-analysis are listed in . Tables 1
and 2.

Network meta-analysis of the

efficacy of tocilizumab, sarilumab,
and olokizumab in RCTs
Tocilizumab is listed at the top left of the
diagonal of the league table (. Table 3) be-
causeitwas associated withthemostfavor-
able SUCRA for the ACR20 response rate.
Tocilizumab showed a significantly higher
ACR20 response rate compared with adal-
imumab or placebo (. Table 3; . Fig. 1).
Tocilizumab, sarilumab, olokizumab, and
adalimumab treatments achieved a signifi-
cant ACR20 response compared to placebo
(. Tables 3 and 4; . Fig. 1). SUCRA simpli-
fies information on the effect of each treat-
ment into a single number to guide the de-
cision-making process. The ranking prob-
ability based on the SUCRA indicated that
tocilizumab had the highest probability of
being considered the best treatment op-
tion for achieving the ACR20 response rate,
followed by sarilumab, olokizumab Q2W,
olokizumab Q4W, adalimumab 40 mg, and
placebo (. Table 5). The ACR50 and 70 re-
sponse rates showed a distribution pattern
similar to that of the ACR20 response rate,
except for olokizumab Q4W, which had
Fig. 1 8 (continued) Bayesian network meta-analysis of randomized controlled trials examining rela- a higher ranking probability than olok-
tive effectiveness according to the number of patients achieving the American College of Rheumatol- izumab Q2W (. Table 3).
ogy 50% response rate (ACR50)
Network meta-analysis of the safety
of tocilizumab, sarilumab, and
olokizumab in RCTs
Concerning AEs and withdrawal due to
AEs, the SUCRA rating likelihood showed
that placebo was the best intervention, fol-
lowed by IL-6 inhibitors (. Tables 4 and 6).
Olokizumab was associated with fewer
AEs than tocilizumab, while tocilizumab
was associated with fewer withdrawals
than olokizumab; the difference was not
statistically significant based on SUCRA
(. Table 6; . Fig. 2).

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Originalien

Inconsistency and sensitivity

analysis
Inconsistency plots were used to assess
network inconsistencies between direct
and indirect estimates, revealing a low pos-
sibility of inconsistencies that might sig-
nificantly affect the network meta-analysis
results. This was confirmed using random-
and fixed-effects models, indicating that
the results of this network meta-analysis
were robust (. Fig. 1).

Discussion
We performed a network meta-analysis
to assess the effectiveness and safety of
tocilizumab, sarilumab, and olokizumab
in patients with active RA showing an
unsatisfactory response to MTX. Based
on ACR20 responses, our network meta-
analysis found that tocilizumab was the
most effective therapy for active RA that
did not respond well to MTX, followed by
sarilumab, olokizumab Q2W, olokizumab
Q4W, adalimumab 40 mg, and placebo.
The ACR50 and 70 response rates followed
a pattern similar to that of the ACR20 re-
sponse rate. No significant differences in
AEs or withdrawals due to AEs were iden-
tified among tocilizumab, sarilumab, and
olokizumab, indicating that both biologi-
cals had a comparable profile.
IL-6 binds to IL-6R to exert biological
effects; once this complex is established,
signaling pathways in the target cell may
be triggered [33]. Direct targeting of the
Fig. 1 8 (continued) Bayesian network meta-analysis of randomized controlled trials examining rela- cytokine or its receptor is a particular in-
tive effectiveness according to the number of patients achieving the American College of Rheumatol- hibitory mechanism of IL-6-blocking bi-
ogy 70% response rate (ACR70) ologics. Effective treatment of RA with
tocilizumab has led to developing new bi-
ologics targeting IL-6 or IL-6R. Different IL-
6 inhibitor, such as anti-IL-6R (sarilumab),
is effective in treating RA, regardless of
whether the specific inhibitory mechanism
involves direct cytokine or receptor target-
ing. Olokizumab is a direct inhibitor of the
IL-6 ligand, which distinguishes it from
already licensed IL-6 receptor inhibitors
[28]. Several antibodies targeting the IL-6
pathway have been developed in addition
to olokizumab [6, 22]. Targeted proteins
(IL-6 or IL6R), the targeted phase of the
IL-6 signaling complex cascade, method
of administration, immunoglobulin type,

6 Zeitschrift für Rheumatologie

Table 4 Network meta-analysis of the safety of all comparators along with odds ratios (upper number in each cell) and 95% credible interval (range)
A. Serious adverse events. OR < 1 signifies that the treatment at the top left is better
Olokizumab Q4W – – – – –
0.89 (0.46–1.69) Placebo – – – –
0.87 (0.47–1.63) 0.99 (0.53–1.86) Olokizumab Q2W – – –
0.71 (0.40–1.25) 0.80 (0.49–1.32) 0.82 (0.46–1.41) Adalimumab – –
0.61 (0.30–1.25) 0.69 (0.48–0.98) 0.70 (0.34–1.41) 0.86 (0.48–1.52) Sarilumab 200 mg –
0.59 (0.27–1.29) 0.66 (0.42–1.02) 0.67 (0.31–1.45) 0.83 (0.43–1.60) 0.96 (0.55–1.68) Tocilizumab
B. Withdrawal due to adverse events
Placebo – – – – –
0.64 (0.41–0.96) Tocilizumab – – – –
0.55 (0.29–1.02) 0.86 (0.40–1.84) Olokizumab Q2W – – –
0.48 (0.29–0.79) 0.75 (0.39–1.46) 0.87 (0.51–1.47) Adalimumab – –
0.44 (0.24–0.80) 0.69 (0.33–1.46) 0.81 (0.48–1.35) 0.92 (0.56–1.54) Olokizumab Q4W –
0.43 (0.30–0.60) 0.67 (0.39–1.18) 0.78 (0.40–1.54) 0.90 (0.52–1.56) 0.98 (0.51–1.87) Sarilumab 200 mg

Table 5 Rank probability of efficacy of Table 6 Rank probability ofsafety ofolok- and/or antibody design are all potential
olokizumab, tocilizumab, and sarilumab izumab, tocilizumab, and sarilumab based distinguishing criteria for these antibodies.
based on the number of patients who on the number of patients who experienced As the current investigation has several
achieved an ACR20, ACR50, and ACR70 re- serious adverse events and withdrawal due
limitations, our results should be inter-
sponse to adverse events
preted with caution. First, a 6-month fol-
Treatment SUCRA Treatment SUCRA
low-up of the safety profile of IL-6-blocking
A. ACR20 A. Adverse events
biologics was inadequate for determining
Tocilizumab 0.851 Olokizumab Q4W 0.802
all relevant safety issues connected with
Sarilumab 200 mg 0.841 Placebo 0.7269 biologicals, particularly for evaluating un-
Olokizumab Q2W 0.615 Olokizumab Q2W 0.654 common occurrences or events requiring
Olokizumab Q4W 0.474 Adalimumab 0.394 longer exposure durations. Second, the
Adalimumab 0.220 Sarilumab 200 mg 0.224 included studies varied in terms of design
Placebo 0.000 Tocilizumab 0.200 and clinical aspects. As a result, these inter-
B. ACR50 B. Withdrawal due to adverse events study differences may have affected our
Tocilizumab 0.970 Placebo 0.990 results. Third, this investigation did not
Sarilumab 200 mg 0.741 Tocilizumab 0.643 thoroughly discuss the effectiveness and
Olokizumab Q4W 0.582 Olokizumab Q2W 0.523 safety of the biologicals. Notably, because
Olokizumab Q2W 0.5027 Adalimumab 0.3543 of the low incidence of AEs, the number of
Adalimumab 0.205 Olokizumab Q4W 0.258 withdrawals due to AEs was insufficient to
Placebo 0.000 Sarilumab 200 mg 0.232 evaluate safety. Fourth, this meta-analysis
included only a limited number of studies.
C. ACR70 SUCRA surface under the cumulative rank-
ing curve, Q2W every 2 weeks, Q4W every This study had insufficient power to inves-
Tocilizumab 1.000
4 weeks tigate biologics’ relative effectiveness and
Sarilumab 200 mg 0.758
safety.
Olokizumab Q2W 0.533 However, this meta-analysis does offer
Olokizumab Q4W 0.479 meaningful information. First, the RCTs
Adalimumab 0.231 employed in this network meta-analysis
Placebo 0.000 were of good quality, with credible find-
ACR20 American College of Rheumatol- ings. Second, the number of patients in
ogy 20% response, ACR50 50% response, each sample ranged from 125 to 1648,
ACR70 70% response, SUCRA surface under
the cumulative ranking curve, Q2W every
with 4439 patients in this study. Third, net-
2 weeks, Q4W every 4 weeks work meta-analysis combines all relevant
data to enable simple head-to-head com-
parisons of various treatment approaches.
Finally, in contrast to individual tests, more
trustworthy and high-resolution findings
have been produced using statistical analy-
sis and by pooling separate research data
[19–21, 31]. To our knowledge, this is

Zeitschrift für Rheumatologie 7

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Fig. 2 8 Bayesian network meta-analysis of randomized controlled trials examining relative safety
according to the number of serious adverse events

8 Zeitschrift für Rheumatologie


Fig. 2 8 (continued) Bayesian network meta-analysis of randomized controlled trials examining rela-
tive safety according to the number of withdrawals due to adverse events
the first Bayesian network meta-analysis to
systematically and concurrently examine
tocilizumab, sarilumab, and olokizumab
in patients with active RA intolerant to or
not responding well to MTX. Until further
RCTs are conducted, this may be the best
evidence available on this issue.
Conclusion
This Bayesian network meta-analysis
demonstrated that tocilizumab, sarilumab,
and olokizumab are more efficacious than
adalimumab. Further, tocilizumab, sar-
ilumab, and olokizumab have comparable
efficacy and safety in patients with RA
who did not respond to MTX. Long-term
trials involving a large number of patients
with active RA who do not respond effec-
tively to MTX are required to assess the
relative effectiveness and safety of these
IL-6 inhibitors.
Corresponding address
Young Ho Lee, MD, PhD
Division of Rheumatology, Department of
Internal Medicine, Korea University Anam
Hospital, Korea University College of Medicine
73, Goryeodae-ro, 02841 Seongbuk-gu, Seoul,
Korea (Republic of)
lyhcgh@korea.ac.kr
Declarations
Conflict of interest. Y. Ho Lee and G. Gyu Song
declare that they have no competing interests.
For this article no studies with human participants
or animals were performed by any of the authors. All
studies mentioned were in accordance with the ethical
standards indicated in each case.
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10 Zeitschrift für Rheumatologie
Zusammenfassung
Vergleich der Wirksamkeit und Sicherheit von Tocilizumab, Sarilumab
und Olokizumab bei Patienten mit aktiver rheumatoider Arthritis:
Netzwerk-Metaanalyse von randomisierten kontrollierten Studien
Ziel: In der vorliegenden Studie wurde die relative Wirksamkeit und Sicherheit von
Olokizumab, Tocilizumab und Sarilumab bei Patienten mit rheumatoider Arthritis (RA)
verglichen, bei denen eine Unverträglichkeit und unzureichende Therapieantwort auf
Methotrexat (MTX) bestand.
Methoden: Es wurde eine Bayes-Netzwerk-Metaanalyse durchgeführt, um direkte und
indirekte Evidenz aus randomisierten kontrollierten Studien (RCT) für die Untersuchung
der Wirksamkeit und Sicherheit von Olokizumab, Tocilizumab und Sarilumab bei
RA-Patienten zu kombinieren, bei denen eine Unverträglichkeit und unzureichende
Therapieantwort auf Methotrexat (MTX) bestand.
Ergebnisse: Die Einschlusskriterien wurden von 6 RCT mit 4439 Patienten erfüllt.
Unter Therapie mit Tocilizumab, Sarilumab, Olokizumab und Adalimumab wurde
eine signifikante ACR20-Responserate (American College of Rheumatology 20 %) im
Vergleich mit Placebo erzielt. Jedoch ging Tocilizumab mit der günstigsten SUCRA
(„surface area using the cumulative ranking curve“) für die ACR20-Responserate einher.
Die Rankingwahrscheinlichkeit auf Grundlage der SUCRA zeigte, dass die Therapie
mit Tocilizumab die höchste Wahrscheinlichkeit für die beste ACR20-Responserate
aufwies, es folgten Sarilumab, Olokizumab alle 2 Wochen (Q2W), Olokizumab
Q4W, Adalimumab 40 mg und Placebo. Die ACR50- und ACR70-Responseraten
wiesen ein Verteilungsmuster auf, das dem der ACR20-Responserate ähnlich war.
Allerdings bestand für Olokizumab Q4W eine höhere Rankingwahrscheinlichkeit als für
Olokizumab Q2W. Das SUCRA-Rating ergab, dass Placebo die beste Intervention mit
den wenigsten unerwünschten Ereignissen (AE) und Therapieabbruch aufgrund von
AE war, es folgten Interleukin(IL)-6-Inhibitoren.
Schlussfolgerung: Tocilizumab, Sarilumab und Olokizumab sind wirksamer als
Adalimumab und weisen eine ähnliche Wirksamkeit und Sicherheit bei RA-Patienten
mit unzureichender Therapieantwort auf MTX auf.
Schlüsselwörter
Tocilizumab · Sarilumab · Olokizumab · Rheumatoide Arthritis · Netzwerk-Metaanalyse
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