OP0079 Ustekinumab is Effective in Inhibiting Radiographic Progression in Patients with Active Psoriatic Arthritis: Integrated Data Analysis of Two Phase 3, Randomized, Placebo-Controlled Studies
Iain B. McInnesChristopher T. RitchlinProton RahmanL. PuigAlice B. GottliebMichael SongB. RandazzoS. LiY. WangAlan M. MendelsohnArthur Kavanaugh
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Abstract:
Objectives
To evaluate the effect of ustekinumab (UST), an IL-12/23 p40 inhibitor, on inhibition of progression of structural damage in patients with active psoriatic arthritis (PsA) at wk24 and wk52 in the PSUMMIT 1 and PSUMMIT 2 trials.Methods
Adult PsA patients with active disease (≥5 SJC and ≥5 TJC; CRP≥0.3mg/dL [ULN 1.0 mg/dL]) despite DMARD and/or NSAID therapy (PSUMMIT 1, n=615; PSUMMIT 2, n=132) or previously treated with DMARD and/or NSAID, and prior anti-TNFα therapy (PSUMMIT 2, n=180) were randomized to UST45mg, 90mg, or PBO at wks 0, 4, and q12wks, thereafter. At wk16, patients with <5% improvement in TJC & SJC entered blinded early escape [EE] (PBO$→ $UST45mg; UST45mg$→ $90mg; 90mg$→ $90mg). No concomitant DMARDs with the exception of MTX (approximately 50% of patients in each study) were permitted. Radiographs of hands and feet were taken at wks 0, 24, and 52 regardless of EE status, or at the time of study drug discontinuation (unless radiographs were completed within the prior 8wks). Erosions and joint space narrowing (JSN) were evaluated by independent readers blinded to treatment, patient IDs and image time sequence using PsA modified van der Heijde-Sharp (vdH-S) method (total score ranging from 0-528). The major secondary endpoint of change from baseline in total vdH-S scores at wk24 was analyzed based on a pre-specified integrated data analysis using data combined from both studies. Imputation of missing data was done using linear extrapolation or median change of 0.Results
Baseline disease characteristics including total vdH-S, TJC, SJC and CRP were comparable between PSUMMIT 1 & 2. In the integrated analyses, both UST 45 mg and 90 mg treated patients demonstrated a significant difference in change from baseline in total vdH-S scores at wk24 vs PBO (Table). Moreover, continued inhibition was demonstrated through wk 52; patients randomized to PBO who initiated UST at wk16 or 24 demonstrated slowing of radiographic progression by wk52 (mean change in total vdH-S wk24 to wk52 of 0.08). These observations were reproduced when PSUMMIT 1 was evaluated alone. In PSUMMIT 2, a demonstrable effect of UST on inhibition of structural damage progression could not be discerned; these results may have been impacted by missing radiographic data, especially among PBO-treated patients (23% missing radiographs).Conclusions
Based upon the pre-specified integrated data analysis, ustekinumab inhibits radiographic progression at wk24.Disclosure of Interest
I. McInnes Grant/research support: Abbott, BMS, Janssen, Pfizer, Roche, Merck/Schering-Plough, and UCB., C. Ritchlin Grant/research support: Amgen, Janssen, and UCB., Consultant for: Abbott, Amgen, Janssen, Regeneron, Roche, and UCB., P. Rahman Grant/research support: Abbott, Amgen, Janssen, Merck/Schering-Plough, and Wyeth., L. Puig Grant/research support: Abbott, Amgen, Celgene, Janssen, Merck/Schering-Plough, and Pfizer., A. Gottlieb Grant/research support: Amgen, Abbott, Celgene, Immune Control, Janssen, Lilly, Novartis, Novo Nordisk, Pfizer, and UCB., Consultant for: Abbott, Actelion, Amgen,Astellas, Belersdorf, BMS, Canfite, Celgene, DemiPsor, Incyte, Janssen, Lilly ICOS, Merck, Novartis, Novo Nordisk, Pfizer, Teva, and UCB., M. Song Employee of: Janssen Research & Development, LLC, B. Randazzo Employee of: Janssen Research & Development, LLC, S. Li Employee of: Janssen Research & Development, LLC, Y. Wang Employee of: Janssen Research & Development, LLC, A. Mendelsohn Employee of: Janssen Research & Development, LLC, A. Kavanaugh Grant/research support: Abbott, Amgen, Janssen, and UCB.DOI
10.1136/annrheumdis-2014-eular.2263Keywords:
Ustekinumab
Discontinuation
Concomitant
Background. Early detection of psoriatic arthritis in patients with psoriasis remains an unmet medical need. Early diagnosis and treatment initiation in patients with psoriatic arthritis decreases the risk of adverse patient outcomes and improves patients quality of life.
Aims. To describe a period between psoriasis and psoriatic arthritis onset and a period between psoriatic arthritis onset and diagnosis in Russian patients with moderate to severe psoriasis.
Materials and methods. Analysis of data from the psoriasis patient registry. Patients aged 18 years and older with an established diagnosis of psoriasis and psoriatic arthritis were included in the analysis. Noninclusion criteria: no data on psoriasis and/or psoriatic arthritis onset (for the period between psoriasis and psoriatic arthritis onset description); no data on psoriatic arthritis onset and/or diagnosis (for the period between psoriatic arthritis onset and diagnosis description).
Results. Sample size for the descriptive characteristic of period between psoriasis and psoriatic arthritis onset was 891 patients; sample size for the descriptive characteristic of period between psoriatic arthritis onset and diagnosis was 849 patients.
Psoriatic arthritis onset preceeded cutaneous manifestation of psoriasis in 2.5% of patients. Concurrent onset of cutaneous psoriasis and psoriatic arthritis (within one year) had 10.7% of patients. In 86.8% of patients, cutaneous manifestation of psoriasis preceded manifestation of psoriatic arthritis.
Exclusively of patients with psoriatic arthritis developed before or concurrently with cutaneous manifestation of psoriasis, the mean duration of period between psoriasis and psoriatic arthritis onset was 13.7 10.3 years, the median [IQR] 12 [619] years.
In 24% of patients psoriatic arthritis was diagnosed 1 year and more after its onset. The mean (SD) period from signs and|or symptoms onset till psoriatic arthritis diagnosis was 3.9 5.0 years; median [IQR] was 2 [14.5] years.
Conclusions. A diagnostic delay in 24% Russian patients with psoriatic arthritis is one year or more. In this subgroup of patients the mean delay in diagnosis of psoriatic arthritis is about 4 years.
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Psoriatic arthritis occurs commonly in those with psoriasis and is associated with progressive joint destruction, physical disability, reduced quality of life and increased mortality. For many patients the currently available treatment options including the anti-TNF treatments are inadequate. Recent data suggest that ustekinumab can provide an effective treatment option in these patients. We discuss the role of ustekinumab in the treatment of psoriatic arthritis and highlight areas requiring further work.
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Psoriatic arthritis is an inflammatory arthritis associated with psoriasis. The IL-23/IL-17 axis is an important pathway in the development of psoriatic disease. Ustekinumab is a fully human monoclonal IgG1 antibody that binds to the p40 subunit of IL-12 and IL-23, which, in turn, inhibits downstream signaling pathways. PSUMMIT-1 and PSUMMIT-2 are two pivotal Phase III trials demonstrating global improvement in primary and secondary outcomes including inhibition of radiographic progression. Therapeutic benefit of ustekinumab for synovitis appears independent of previous disease modifying antirheumatic disease or anti-TNF exposure. At present, the data support the use of ustekinumab in the treatment of psoriatic arthritis after the failure of NSAIDs and conventional disease modifying antirheumatic diseases as an alternative to, or after failure of an anti-TNF agent.
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Abstract: Psoriatic arthritis occurs in 30% of psoriasis patients, and the treatment can be challenging in some patients. Recently, the US Food and Drug Administration approved ustekinumab, a fully human monoclonal antibody, for the management of psoriatic arthritis. In this article, we review large-scale randomized clinical trials addressing the efficacy and safety profile of ustekinumab for the treatment of psoriatic arthritis. Keywords: psoriatic arthritis, psoriasis, ustekinumab
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Ustekinumab, which is approved for the treatment of moderate to severe psoriasis, has been shown in phase II clinical trials to be efficacious in controlling the signs and symptoms of psoriatic arthritis. Ustekinumab appears to be well tolerated, but its longterm safety profile is not yet known.
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Background: Psoriasis is a chronic inflammatory disease involving the skin and/or joints. Till 2016, there were five biologic agents for psoriatic arthritis treatment in Taiwan: etanercept, adalimumab, golimumab, ustekinumab, and secukinumab. Although European guidelines recommend tumor necrosis factor-α (TNF-α) inhibitors as the first-line biologic agents for axial disease of psoriatic arthritis, the drug survival of biologic agents in Asian populations remains unclear. Objectives: We investigated 5-year drug survival of biologic agents in patients with psoriatic arthritis. Methods: We used Kaohsiung Medical University Hospital Research Database to evaluate real-world 5-year drug survival of biologic agents for psoriatic arthritis in a medical center from southern Taiwan. Results: The 5-year drug survival rates of ustekinumab, etanercept, and adalimumab were significantly different. Ustekinumab and etanercept showed higher 5-year survival rates for psoriatic disease than adalimumab. Golimumab and secukinumab had a short follow-up time to obtain a conclusive 5-year survival rate. Conclusion: Considering that TNF-α inhibitors are often the first-line biologic agents for psoriatic arthritis in guidelines in western countries, the finding that ustekinumab is superior to TNF-α inhibitor adalimumab in terms of 5-year survival for psoriatic disease may imply that the therapeutic response of biologic agents may differ between different ethnic groups.
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Ustekinumab is a human monoclonal antibody that binds to the shared p40 subunit of interleukin (IL) 12 and IL-23. It is approved in the United States for adults (>18 years) with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy. In 1 phase 2 trial of ustekinumab for treatment of psoriatic arthritis, joint disease improved.We report 4 cases of ustekinumab monotherapy for plaque psoriasis that resulted in disabling flares of known psoriatic arthritis or unmasked previously occult joint disease. In all of our cases, psoriasis improved dramatically with ustekinumab therapy while psoriatic arthritis flared.Despite early results of a phase 2 ustekinumab trial suggesting efficacy for both plaque psoriasis and psoriatic arthritis, our case series raises concern that ustekinumab may unmask or aggravate joint disease in selected patients. These data underscore the need for further investigation of ustekinumab's effects on psoriatic arthritis.
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Given the potential consequences of joint damage for patients with psoriatic arthritis, we believe that the optimization of screening methods and the investigation of arthritis in patients with psoriasis are a medical priority. It is very useful to identify predictors of arthritis in patients with psoriasis. In fact, there is a consensus among doctors that the large gap between the diagnosis of psoriasis and that of psoriatic arthritis should be narrowed. In order to better manage patients with psoriasis, the authors review and discuss recent publications on the evidence of current predictors of arthritis in patients with psoriasis.
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