Disease-specific composite measures for psoriatic arthritis are highly responsive to a Janus kinase inhibitor treatment that targets multiple domains of disease

Abstract

BackgroundThe multiple disease domains affected in psoriatic arthritis (PsA) may make composite endpoints appropriate for assessing changes in disease activity over time. Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA. Data from two phase 3 studies of patients with PsA were used to evaluate the effect of tofacitinib on composite endpoints.MethodsOral Psoriatic Arthritis triaL (OPAL) Broaden was a 12-month study of tumor necrosis factor inhibitor (TNFi)-naïve patients with an inadequate response to at least one conventional synthetic disease-modifying anti-rheumatic drug; OPAL Beyond was a 6-month study of patients with inadequate response to TNFi. Patients with active PsA received tofacitinib 5 or 10 mg doses twice daily (BID), adalimumab 40 mg subcutaneous injection once every 2 weeks (OPAL Broaden only), or placebo advancing at month 3 to tofacitinib 5 or 10 mg BID. The disease-specific composites were Psoriatic Arthritis Disease Activity Score (PASDAS), Disease Activity Index for Reactive Arthritis/Psoriatic Arthritis (DAPSA), and Composite Psoriatic Disease Activity Index (CPDAI). Change from baseline in composite endpoints was also assessed for minimal disease activity (MDA) responders versus non-responders.ResultsOverall, 422 patients from OPAL Broaden and 394 patients from OPAL Beyond were treated. The mean changes from baseline to month 3 for tofacitinib 5 mg BID, tofacitinib 10 mg BID (standard error; effect size) were OPAL Broaden: PASDAS, −2.0 (0.14; 1.73), −2.4 (0.14; 2.4); DAPSA, −20.2 (1.72; 0.9), −24.4 (1.73; 1.23); and CPDAI, −2.9 (0.34; 1.03), −4.2 (0.36; 1.53); OPAL Beyond: PASDAS, −1.9 (0.14; 1.53), −2.1 (0.14; 1.84); DAPSA, −22.5 (1.67; 0.81), −21.0 (1.70; 0.84); and CPDAI, −3.3 (0.31; 1.41), −3.4 (0.31; 1.45). Greater changes from baseline to month 3 (P ≤0.05) were seen with both doses of tofacitinib versus placebo for all endpoints except CPDAI for tofacitinib 5 mg BID in OPAL Broaden. Effect sizes generally increased from 3 to 6 months. Mean changes from baseline were greater in MDA responders than MDA non-responders for all composite endpoints across all time points and treatments.ConclusionsThis analysis suggests that disease-specific composite measures are appropriate for evaluating treatment efficacy on multiple disease domains in PsA.Trial registrationOPAL Broaden: ClinicalTrials.gov Identifier: NCT01877668, first posted June 12, 2013; OPAL Beyond: ClinicalTrials.gov Identifier: NCT01882439, first posted June 20, 2013.Electronic supplementary materialThe online version of this article (10.1186/s13075-018-1739-0) contains supplementary material, which is available to authorized users.

<p>Tofacitinib in the management of active psoriatic arthritis: patient selection and perspectives</p>

“…Tofacitinib (Xeljanz, Pfizer Inc.) is an orally administered inhibitor of predominantly JAK1 and JAK3, with functional selectivity over JAK2. 4,13,14 Blockade of the JAK receptor downregulates the production of cytokines important in the pathogenesis of PsA, including TNF-α, IL-17, IL-6, IL-23. 14,15 Tofacitinib is currently approved for the treatment of PsA, rheumatoid arthritis, and ulcerative colitis.…”

“…Psoriatic arthritis (PsA) is a chronic, inflammatory musculoskeletal disease that is characterized by peripheral arthritis, enthesitis, dactylitis, and spondylitis with or without nail and skin lesions. 1,2 It is a systemic disease that develops in up to 40% of psoriasis patients in their lifetime [3][4][5] with manifestations that include pain, swelling, stiffness, and entheses of the peripheral joints and/or axial skeleton. Dactylitis, fusiform full thickness swelling of fingers or toes, can develop in about half of individuals with PsA.…”

Measuring Outcomes in Psoriatic Arthritis

“…MDA criteria have good responsiveness to change and are able to differentiate between drug plus placebo (101,102,108–110) and active comparators (111,112). MDA criteria have good responsiveness in LOS (113).…”

“…DAPSA has good responsiveness to change in trials and is able to differentiate between drug and placebo (101,108,115,119), but the effect size is lower than that of the PASDAS in most trial post hoc analyses (101,119,120). DAPSA has lower responsiveness than other composite disease measures in LOS (121).…”

Results of studying the clinical efficacy and safety of tofacitinib in the treatment of psoriatic arthritis

“…В последние годы для лечения ПсА используется также ингибитор Янус-киназ (JAK) тофацитиниб (ТОФА), который по влиянию на основные клинические проявления ПсА сопоставим с ингибитором ФНОα адалимумабом (АДА) [7,8]. Установлено, что ТОФА, как и ингибиторы ФНОα, ИЛ12/23, ИЛ17, обладает способностью существенно замедлять прогрессирование структурных изменений при ПсА [9][10][11].…”