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A short history of biological therapy for psoriatic arthritis

P. Mease

Swedish Medical Center, Division ABSTRACT diseases, including rheumatoid arthritis

of Rheumatology Research, Seattle, Psoriatic arthritis (PsA) is an inflam- (RA), psoriatic arthritis (PsA), ankylos-
Washington University of Washington matory disease characterised by the ing spondylitis (AS), psoriasis, inflam-
School of Medicine, Seattle,
clinical domains of arthritis, enthesitis, matory bowel disease (IBD), and multi-
Washington, USA.
dactylitis, spondylitis, and psoriasis, ple sclerosis (MS) as well as many oth-
Philip Mease, MD
often causing significant functional dis- ers, along with key developments in the
Please address correspondence to: ability, loss of quality of life, and prema- capacity to identify and produce protein
Dr Philip J. Mease,
Seattle Rheumatology Associates,
ture mortality. Prior to the introduction antibody therapeutics directed at inhib-
601 Broadway, Suite 600, of targeted biologic medications, such as iting specific cytokines and cells, came
Seattle, WA 98122, USA. TNF inhibitors, the capacity to control together to begin the era of biologic
E-mail: disease activity was limited, with only therapy of autoimmune disease. The
Received and accepted on September 25, modest effects noted in most patients first diseases to be targeted were promi-
2015. with traditional oral medications such as nent autoimmune diseases in the fields
Clin Exp Rheumatol 2015; 33 (Suppl. 93): methotrexate and sulfasalazine. The in- of rheumatology, dermatology, gastro-
S104-S108. troduction of TNF inhibitors substantial- enterology, and neurology, specifically
Copyright Clinical and ly changed the outlook of PsA patients, RA, psoriasis, IBD, and MS. Many of
Experimental Rheumatology 2015. yielding significant response in all rele- the molecular mechanisms driving these
vant clinical domains and demonstrating diseases have overlapping features and
Key words: psoriatic arthritis, the capacity to inhibit progressive struc- to an extent, development of therapeu-
psoriasis, TNF inhibition, IL12-23 tural damage of joints. However, not all tics overlapped, in other ways they have
inhibition, IL17 inhibition, patients responded to these agents and diverged, with the finding that drugs
IL23 inhibition many patients displayed initial response that provide efficacy in one disease may
which waned over time, partly due to im- not do so in another.
munogenicity (development of antibod- In the field of psoriasis, based on un-
ies which blocked full therapeutic effect derstanding of the key role of T lym-
of the biologic protein), or because of phocytes in disease pathogenesis, the
poor tolerability and/or adverse events. first biologic agents to be studied were
Thus, it has been important to develop co-stimulatory blockade agents, agents
new medicines which target other key that inhibit the second signal of lym-
cytokines and immunologic pathways, phocyte activation. The initial drugs
including ustekinumab which inhibits tested were alefacept and efaluzimab.
both IL12 and IL23 and thus is felt to These proved to be modestly efficacious
work in both the TH1 and TH7 pathways and were approved for the treatment of
of inflammation, has been approved for psoriasis. However, issues such as the
the treatment of PsA as well as psoriasis. potential for reduction of CD4 positive
IL17 inhibitors, including secukinumab T cells with alefacept, and unexpected
and ixekizumab have demonstrated sig- episodes of serious infection with efali-
nificant effectiveness in psoriasis and zumab, leading to its withdrawal, as well
PsA; abatacept, which modulates T cell as lesser degree of efficacy compared to
activity via inhibition the second signal the next wave of biologics, the TNF in-
of T cell activation is under study. This hibitors, led to cessation of use of these
article provides an historical overview agents for psoriasis. Phase 2 studies in
of this revolution; details of specific bio- PsA showed modest efficacy (1, 2), and
logical therapies will be provided in ad- thus proof-of-concept for T cell modula-
jacent articles in this supplement. tion role in PsA, but ultimately approval
Competing interests: P. Mease has in PsA was not sought because of poor
received research grants, consultancy, History of biological therapy for success in psoriasis.
and/or speakers fees from: AbbVie,
psoriatic arthritis
Amgen, Biogen Idec, Bristol Myers Squibb,
Celgene, Covagen, Crescendo, Genentech, In the 1990s, our deepening understand- TNF inhibitors
Janssen, Lilly, Merck, Novartis, Pfizer, ing of the molecular and cellular patho- The introduction of the TNF inhibitors
and UCB. genesis of autoimmune inflammatory (TNFi), the first biologic agents used

A short history of biological therapy for PsA / P. Mease

in the treatment of rheumatologic dis- sequent phase 3 trials with these two in clinical registries, such as the Con-
ease, in the late 1990s greatly strength- agents, which included radiographic as- sortium of Rheumatology Researchers
ened the capacity to achieve states of sessment of joint damage and response of North America (Corrona) (14), and
low disease activity or remission for to therapy, led to regulatory approval biologic registries in countries such as
conditions such as RA and the spon- for PsA (7, 8). Soon, other anti-TNFs, Norway (15) and Denmark (16).
dyloarthritides, including PsA. In parts including adalimumab, golimumab, It appears that average survival of
of the world where these therapies are and certolizumab pegol were studied, PsA patients on TNFi is in the range of
affordable, these agents have become showed similar degrees of effective- 2-4 years for the first TNFi tried and
the gold standard for management of ness and safety, and are now approved shorter duration for subsequent TNFi.
these diseases. The first proof-of-con- for PsA (9-11). The science of outcome Reasons for loss of effect of the TNFi
cept study of TNF inhibition in PsA measurement of PsA has also advanced appear to be multifactorial. In some,
was with etanercept. In an investigator- in parallel, resulting in more refined and intolerability or serious adverse effects
initiated study in Seattle, Mease and reliable assessment (12). may occur with time, in others, disease
Goffe explored the efficacy and safety However, even with the success of anti- activity may change and increase de-
of etanercept in 60 patients with mod- TNF therapy in general, not all patients spite the use of the TNFi; and in oth-
erate to severe PsA (3). achieve or maintain satisfactory states ers, gradual loss of efficacy may occur.
Given the paucity of previous clinical for a variety of reasons. Some patients Loss of efficacy may be due partly to
trials in PsA, there was little in the way may have a contraindication to use of development of immunogenicity to the
of a roadmap for assessing efficacy. The TNFi, for example those with multiple therapeutic protein, i.e. development
Psoriatic Arthritis Response Criteria sclerosis, and should not have a TNFi of an antibody response which may
(PsARC) had been used in a previous initiated. Others may have a relative wholly or partly neutralise treatment
trial of sulfasalazine in PsA (4), other- contraindication, such as severe conges- effect. This phenomenon has most
wise, measures used were derived from tive heart failure, lymphoma, or living clearly been documented with chimeric
RA and psoriasis trials (ACR response or working in an area endemic for tuber- antibody constructs such as infliximab,
criteria, Health Assessment Question- culosis or invasive fungal infections, in in which the antibody response may
naire, SF-36, Psoriasis Area and Sever- which case the patient or physician may be directed against the murine portion
ity Index (PASI), etc (5). In discussions be reluctant to initiate TNFi therapy. A of the molecule (17, 18). Neutralising
with the FDA, it was determined that significant number of patients do not re- antibodies appear more likely to oc-
patients already taking methotrex- spond to TNFi therapy. Depending what cur in monoclonal antibody constructs
ate (MTX) could continue to take this one considers a desirable response, in compared to the soluble receptor con-
drug, and be stratified to etanercept or typical clinical trials of TNFi therapy struct exemplified by etanercept (17,
placebo. in PsA, at least 40% do not achieve 18). Concomitant use of methotrexate
As it developed, half of the patients an ACR 20 response, at least 60% do may inhibit antibody formation against
in the trial were on background MTX, not achieve an ACR 50 response and TNFi (17, 18).
so the trial naturally yielded 4 similar at least 80% do not achieve an ACR Indirect evidence that immunogenicity
arms: etanercept versus MTX, with or 70 response by 24 weeks of treatment may shorten duration of TNFi effec-
without MTX background. A minimum (13). Reasons for primary non-response tiveness is derived from registry stud-
of 3 tender and swollen joints was al- include true lack of clinical effect, in- ies, in which it has been demonstrated
lowed, partly in order to understand tolerability, serious adverse effects, as that infliximab survival is shorter in PsA
the response of the oligoarticular form well as other issues such as structural when this agent is used as monotherapy
of PsA (many of these design features damage or the presence of concomitant versus used in combination with metho-
continue to be used in PsA trials to fibromyalgia which does not respond to trexate (14, 15). By contrast, this differ-
date). At the 12 week primary end- immunomodulatory therapy and thus ence has not been noted with etanercept,
point of the study, highly statistically blunt assessed therapeutic response. potentially resulting from less immu-
significant improvement was observed Sometimes such a primary non-re- nogenicity associated with this agent
in all clinical domains measured in the sponder will have a response when a (14). In sum, many PsA patients either
etanercept arm of the study, and no new second TNFi is tried, but registry data do not initially achieve or gradually lose
safety issues emerged. Presence or ab- suggest that achievement of a good re- response to TNFi, generating a need for
sence of background MTX did not in- sponse is not as likely in patients who therapies with different mechanisms
fluence outcomes. have demonstrated non-response to tri- of action and demonstrated ability to
In parallel, Antoni (Germany) and oth- al of a first TNFi. In those who do have modify disease activity both de novo
ers were studying infliximab in PsA in a satisfactory response to a first TNFi, and post TNFi inadequate response.
a similarly designed trial (6). This too we are learning that survival on the Furthermore, development of therapies
showed significant effect. In addition to TNFi, i.e. durability of a satisfactory with different administration frequency
arthritis and skin disease, improvement response, can be quite variable, ranging and improved safety profile appeals to
was seen in enthesitis and dactylitis, from months to many years. The data patient and physician preference.
also key clinical domains in PsA. Sub- for this comes from observations made A caveat about the above referenced

A short history of biological therapy for PsA / P. Mease

trials is that there are several disparate established for many years. Trials in Co-stimulatory blockade
ways in which PsA may present clini- early patients are now underway. modulating T lymphocyte function
cally. The predominant clinical pres- Abatacept
entation is polyarticular disease. Some Targeting the TH17 cell axis in PsA Abatacept is a co-stimulatory blockade
patients may predominantly manifest Studies conducted over the last few agent which inhibits T cell activation
oligoarticular (<5 involved joints) dis- years have shown that IL23, IL17, and through second signal inhibition. The
ease or arthritis mutilans, a rare form in IL22, key cytokines involved in the first signal of T cell activation is the
which the distal joints become severely pathway of TH17 lymphocyte activa- interaction between the major histocom-
damaged and may dissolve. These sub- tion and effector activities (Fig. 1) (19), patibility complex MHC and the T cell
sets have not been adequately assessed are richly expressed in psoriatic skin receptor (TCR). A second signal is
in standard clinical trials of PsA. Al- lesions and the blood and synovium of needed for full T cell activation. A num-
though subset analysis of trials sug- PsA patients. Their roles in pathophysi- ber of receptor-ligand pairs act as second
gests that these patients also respond to ology include hyperproliferation of ke- signals, including CD80/86 on an anti-
biologic therapy, an in depth study of ratinocytes, promotion of synovitis, and gen presenting cell and CD28 on the T
response has not been conducted. activation of a variety of effector cells cell surface. The natural inhibitor of this
Axial disease, e.g. sacroiliitis, syn- involved in cartilage and bone destruc- second signal interaction is CTLA4Ig.
desmophyte formation, and facet ar- tion (20-24). Trials of therapeutic agents This molecule is mimicked by abata-
thropathy can occur in PsA. Such spon- which inhibit IL12/23, IL23 and IL17, cept, which by binding to CD80/86, in-
dylitis has not been assessed in PsA detailed in other articles in this supple- hibits CD28 binding, thus inhibiting the
clinical trials with definitive clinical ment, demonstrate significant benefit second signal and reducing T cell acti-
or imaging metrics due to the variable in various clinical domains of psoriasis vation. Abatacept is approved for the
nature in which spondylitis presents and PsA (25-27). treatment of RA. A phase 2 study of 170
and the amount of effort and resource PsA patients, using various doses of the
needed to assess this domain. Thus, our Biologic agents approved for RA intravenous formulation of abatacept,
assumptions about treatment of spon- are they beneficial for PsA? demonstrated significant improvement
dylitis in PsA has been derived from Brief descriptions of biologic agents ap- of ACR20 response (28). Magnetic reso-
outcomes of ankylosing spondylitis proved for the treatment of RA, that have nance imaging (MRI) study of hands or
trials. There has been very little study been tested or are being tested in PsA, feet at 24 weeks demonstrated improved
of treatment of early PsA; most tri- which are not detailed in adjacent articles synovitis, erosion, and osteitis scores.
als have enrolled patients with disease in this supplement are presented below. Skin psoriasis responses were modest.

Fig. 1. T Cell differentiation pathways (19).

A short history of biological therapy for PsA / P. Mease

This medication is now in development 35) demonstrating modest effect on ar- and outcome measures in collaboration
in its subcutaneous form for the treat- thritis; however,virtually no effect on with the Outcome Measures in Clini-
ment of PsA. skin psoriasis has been noted. cal Trials (OMERACT) association,
collaborate in translational research,
IL-6 inhibition IL-1 inhibition develop evidence-based treatment rec-
Interleukin 6 (IL6) is a pleiotropic pro- Interleukin 1 is a cytokine produced ommendations, and pursue education-
inflammatory cytokine which has a in excessive amounts in inflammatory al initiatives globally. GRAPPA is a
significant role in RA pathogenesis and conditions such as RA and PsA. The unique example of two different disci-
has been demonstrated to be elevated biological agent, anakinra, and IL-1 plines of medicine, rheumatology and
in PsA synovitis and psoriasis skin le- inhibitor, is approved for the treatment dermatology, working collaboratively
sions (29). Tocilizumab, an IL-6 recep- of RA, but clinically has proven disap- in research and education efforts with
tor blocker, is approved for RA. Case pointing and is used primarily for adult a disease that crosses over traditional
reports of its use in PsA have shown onset juvenile arthritis. Anakinra has medical discipline boundaries.
both positive and negative results (30). not been shown to be efficacious in
PsA; a placebo-controlled study which Conclusion
Clazakizumab included MRI and synovial biopsy as- Our capacity to achieve therapeutic
Clazakizumab is a direct IL-6 inhibitor sessment did not demonstrate a differ- benefit for the heterogeneous clinical
that has demonstrated efficacy in RA ence between placebo and anakinra in aspects of PsA, including arthritis, en-
(31). This agent was studied in a phase PsA (36). thesitis, dactylitis, spondylitis, and pso-
2 trial with 165 PsA patients, 70% riasis has been significantly improved
of whom were on background MTX Collateral benefits of the by the introduction of parenteral biolog-
(32). ACR20 response was observed development of biologics for the ic therapies. The first introduced biolog-
in 29/46/52/39% of patients in the pla- treatment of PsA ic therapies which inhibit TNF- have
cebo/25 mg/100 mg/200 mg monthly Increased interest in PsA globally gen- achieved enduring states of low disease
groups at the Week 16 primary endpoint, erated by these treatment advances, as activity or remission in many, but not
which was statistically significant in the well as funding by government, the all patients. Furthermore, efficacy may
100 mg group. PASI 75 responses were pharmaceutical industry, and private be lost over time due to a number of
observed in 12/15/17/5% of placebo/25 donors, has led to an exponential in- factors, including issues of tolerability
mg/100 mg/200 mg groups. Improve- crease of interest in PsA. Increases and safety or development of immuno-
ments in enthesitis and dactylitis were have been seen in genetic, translation- genicity. Thus, it has been important to
most noted in the 100 mg group. al, clinical, outcomes, and treatment develop and test biologic agents with a
The safety profile included issues ex- research over the last 15 years, as well different mechanism of action than TNF
pected for an IL-6 inhibiting agent, as educational efforts directed toward inhibition. Agents which have shown ef-
including increased risk for infection clinicians and patients, and interest fectiveness in psoriasis, as well as PsA
and elevation of hepatic transaminases by regulatory and other governmental thus far tested, and have been approved
and lipids. Demonstration of appar- bodies. Dafna Gladman has supervised for use or are in development include
ently greater effect in joints than skin an exemplary PsA clinical registry in those which inhibit IL-12/23 usteki-
suggests a differential role for IL6 in Toronto for decades and is now joined numab, IL-17 secukinumab, ixekizum-
the pathogenesis of synovitis as com- by several national clinical registries ab, IL-23 guselkumab, tildrikizumab,
pared to psoriasis. A true dose effect in countries such as the United States BI-655066, co-stimulatory blockade
was not demonstrated, given the under- (Corrona), Sweden, Denmark, Norway, agents abatacept, as well as other
performance of the highest dose group, United Kingdom, Italy, and numerous agents with novel mechanisms of action
due partly to use of non-responder im- other nations and centers. These regis- in the therapeutic pipeline. Over time,
putation analysis and a greater number tries provide important data about the we have become more sophisticated in
of adverse effects and dropouts in the natural history of disease, outcomes, our ability to assess disease activity in
higher dose group. co-morbidities. An international group PsA, which along with our improved
of investigators from rheumatology understanding of disease pathogenesis
B lymphocyte inhibition and dermatology has come together and development of drugs targeting key
Rituximab, which works by ablating B in an organisation known as GRAPPA pro-inflammatory pathways, is leading
lymphocytes, is approved for the treat- (Group for Research and Assessment to more rational and targeted treatment
ment of RA and vasculitis. Although of Psoriasis and Psoriatic Arthritis). and better outcomes for patients with
some B cell aggregation has been noted Since its inception in 2003, this group PsA. Research and awareness about PsA
in PsA synovium (33), B lymphocytes has now grown to over 600 rheuma- has expanded rapidly partly due to the
are not considered to be as prominent tologists, dermatologists, and other successes achieved by biologic therapy,
a part of the pathophysiology of PsA interested stakeholders, including rep- bringing two disciplines of medicine,
as RA. Small cohorts of PsA patients resentatives of patient service leagues, rheumatology and dermatology, to work
have been treated with rituximab (34, to develop and refine a disease core set together collaboratively.

A short history of biological therapy for PsA / P. Mease

Acknowledgements Psoriasis Severity Index (NAPSI), Modified egative spondylarthritides. Arthritis Rheum
Nail Psoriasis Severity Index (mNAPSI), 2008; 58: 2307-17.
Catherine Loeffler assisted with the
Mander/Newcastle Enthesitis Index (MEI), 24. SUZUKI E, MELLINS ED, GERSHWIN ME et
manuscript preparation. Leeds Enthesitis Index (LEI), Spondyloar- al.: The IL-23/IL-17 axis in psoriatic arthri-
thritis Research Consortium of Canada tis. Autoimmun Rev 2014; 13: 496-502.
References (SPARCC), Maastricht Ankylosing Spondy- 25. TAUSEND W, DOWNING C, TYRING S: Sys-
1. MEASE PJ, GLADMAN DD, KEYSTONE EC: litis Enthesis Score (MASES), Leeds Dacty- tematic review of interleukin-12, interleu-
Alefacept in combination with methotrexate litis Index (LDI), Patient Global for Psoriatic kin-17, and interleukin-23 pathway inhibitors
for the treatment of psoriatic arthritis: Re- Arthritis, Dermatology Life Quality Index for the treatment of moderate-to-severe chron-
sults of a randomized, double-blind, placebo- (DLQI), Psoriatic Arthritis Quality of Life ic plaque psoriasis: ustekinumab, briakinum-
controlled study. Arthritis Rheum 2006; 54: (PsAQOL), Functional Assessment of Chron- ab, tildrakizumab, guselkumab, secukinumab,
1638-45. ic Illness Therapy-Fatigue (FACIT-F), Pso- ixekizumab, and brodalumab. J Cutan Med
2. PAPP K, MEASE P, GAROVOY M et al.: Efali- riatic Arthritis Response Criteria (PsARC), Surg 2014; 18: 156-69.
zumab in patients with psoriatic arthritis: re- Psoriatic Arthritis Joint Activity Index (PsA- 26. LEONARDI CL, GORDON KB: New and
sults of a phase II randomized double-blind JAI), Disease Activity in Psoriatic Arthritis emerging therapies in psoriasis. Semin Cutan
placebo controlled study. J Cutan Med Surg (DAPSA), and Composite Psoriatic Disease Med Surg 2014; 33 (Suppl. 2): S37-41.
2006 11: 57-66. Activity Index (CPDAI). Arthritis Care Res 27. MEASE PJ: Inhibition of interleukin-17, inter-
3. MEASE PJ, GOFFE BS, METZ J et al.: Etaner- (Hoboken) 2011; 63 (Suppl. 11): S64-85. leukin-23 and the TH17 cell pathway in the
cept in the treatment of psoriatic arthritis and 13. MEASE P: Psoriatic arthritis and spondyloar- treatment of psoriatic arthritis and psoriasis.
psoriasis: a randomised trial. Lancet 2000; thritis assessment and management update. Curr Opin Rheumatol 2015; 27: 127-33.
356: 385-90. Curr Opin Rheumatol 2013; 25: 287-96. 28. MEASE P, GENOVESE MC, GLADSTEIN G
4. CLEGG DO, REDA DJ, MEJIAS E et al.: 14. MEASE P, COLLIER D, KARKI N et al.: et al.: Abatacept in the treatment of patients
Comparison of sulfasalazine and placebo in Persistence and predictors of biologic TNFi with psoriatic arthritis: results of a six-month,
the treatment of psoriatic arthritis. A Depart- therapy among biologic nave psoriatic ar- multicenter, randomized, double-blind, place-
ment of Veterans Affairs Cooperative Study. thritis patients in a US registry. Arthritis and bo-controlled, phase II trial. Arthritis Rheum
Arthritis Rheum 1996; 39: 2013-20. Rheum 2014; 66 (S10): abs 1853. 2011; 63: 939-48.
5. MEASE PJ: Psoriatic arthritis: update on patho- 15. FAGERLI KM, LIE E, van der HEIJDE D et 29. FONSECA JE, SANTOS MJ, CANHAO H et al.:
physiology, assessment and management. Ann al.: The role of methotrexate co-medication Interleukin-6 as a key player in systemic
Rheum Dis 2011; 70 (Suppl. 1): i77-84. in TNF-inhibitor treatment in patients with inflammation and joint destruction. Autoim-
6. ANTONI CE, KAVANAUGH A, KIRKHAM B et psoriatic arthritis: results from 440 patients mun Rev 2009; 8: 538-42.
al.: Sustained benefits of infliximab therapy included in the NOR-DMARD study. Ann 30. COSTA L, CASO F, CANTARINI L et al.: Effi-
for dermatologic and articular manifesta- Rheum Dis 2014; 73: 132-7. cacy of tocilizumab in a patient with refrac-
tions of psoriatic arthritis: results from the 16. JORGENSEN TS, KRISTENSEN LE, CHRIS- tory psoriatic arthritis. Clin Rheumatol 2014;
infliximab multinational psoriatic arthritis TENSEN R et al.: Effectiveness and drug ad- 33: 1355-7.
controlled trial (IMPACT). Arthritis Rheum herence of biologic monotherapy in routine 31. MEASE P, STRAND V, SHALAMBERIDZE L
2005; 52: 1227-36. care of patients with rheumatoid arthritis: a et al.: A phase II, double-blind, randomised,
7. MEASE P, KIVITZ A, BURCH F et al.: Etaner- cohort study of patients registered in the Dan- placebo-controlled study of BMS945429
cept treatment of psoriatic arthritis: safety, ish biologics registry. Rheumatology (Ox- (ALD518) in patients with rheumatoid ar-
efficacy, and effect on disease progression. ford) 2015. thritis with an inadequate response to metho-
Arthritis Rheum 2004; 50: 2264-72. 17. THOMAS SS, BORAZAN N, BARROSO N et trexate. Ann Rheum Dis 2012; 71: 1183-9.
8. ANTONI C, KRUEGER GG, de VLAM K et al.: al.: Comparative immunogenicity of TNF in- 32. MEASE PJ, GOTTLIEB A, BERMAN A et al.:
Infliximab improves signs and symptoms of hibitors: impact on clinical efficacy and tol- A phase IIb, randomized, double-blind, pla-
psoriatic arthritis: results of the IMPACT 2 erability in the management of autoimmune cebo-controlled, dose-ranging, multicenter
trial. Ann Rheum Dis 2005; 64: 1150-7. diseases. A systematic review and meta-anal- study to evaluate the efficacy and safety of
9. MEASE P, GLADMAN D, RITCHLIN C: Adali- ysis. BioDrugs 2015; 29: 241-58. clazakizumab, an anti-IL-6 monoclonal anti-
mumab in the treatment of patients with mod- 18. ZISAPEL M, ZISMAN D, MADAR-BALAKIR- body, in adults with active psoriatic arthritis.
erately to severely active psoriatic arthritis: SKI N et al.: Prevalence of TNF-alpha block- Arthritis Rheum 2014; 66 (S10, abstract 952).
Results of ADEPT. Arthritis Rheum 2005; 58: er immunogenicity in psoriatic arthritis. J 33. CELIS R, PLANELL N, FERNANDEZ-SUEIRO
3279-89. Rheumatol 2015; 42: 73-8. JL et al.: Synovial cytokine expression in pso-
10. KAVANAUGH A, MCINNES I, MEASE P et al.: 19. PATEL DD, LEE DM, KOLBINGER F et al.: riatic arthritis and associations with lymphoid
Golimumab, a new human tumor necrosis Effect of IL-17A blockade with secukinumab neogenesis and clinical features. Arthritis Res
factor alpha antibody, administered every four in autoimmune diseases. Ann Rheum Dis Ther 2012; 14: R93.
weeks as a subcutaneous injection in psoriatic 2013; 72 (Suppl. 2): ii116-23. 34. MEASE PJ: Is there a role for rituximab in the
arthritis: Twenty-four-week efficacy and safe- 20. FRLETA M, SIEBERT S, McINNES IB: The treatment of spondyloarthritis and psoriatic
ty results of a randomized, placebo-controlled interleukin-17 pathway in psoriasis and pso- arthritis? J Rheumatol 2012; 39: 2235-7.
study. Arthritis Rheum 2009; 60: 976-86. riatic arthritis: disease pathogenesis and pos- 35. MEASE P, KAVANAUGH A, GENOVESE M et
11. MEASE PJ, FLEISCHMANN R, DEODHAR AA sibilities of treatment. Curr Rheumatol Rep al.: Rituximab in psoriatic arthritis provides
et al.: Effect of certolizumab pegol on signs 2014; 16: 414. modest clinical improvement and reduces ex-
and symptoms in patients with psoriatic ar- 21. NESTLE FO, KAPLAN DH, BARKER J: Psoria- pression of inflammatory biomarkers in skin
thritis: 24-week results of a Phase 3 double- sis. N Engl J Med 2009; 361: 496-509. lesions. Arthritis Rheum 2010; 62 (10 Suppl.):
blind randomised placebo-controlled study 22. RAYCHAUDHURI SP: Role of IL-17 in pso- S818.
(RAPID-PsA). Ann Rheum Dis 2014; 73: 48- riasis and psoriatic arthritis. Clin Rev Allergy 36. CUNNANE G, MADIGAN A, MURPHY E et al.:
55. Immunol 2013; 44: 183-93. The effects of treatment with interleukin-1
12. MEASE PJ: Measures of psoriatic arthritis: 23. JANDUS C, BIOLEY G, RIVALS JP et al.: In- receptor antagonist on the inflamed synovial
Tender and Swollen Joint Assessment, Pso- creased numbers of circulating polyfunction- membrane in rheumatoid arthritis. Rheuma-
riasis Area and Severity Index (PASI), Nail al Th17 memory cells in patients with seron- tology (Oxford) 2001; 40: 62-9.