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

Abstract

Background: The 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.

Methods: Oral 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.

Results: Overall, 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.

Conclusions: This analysis suggests that disease-specific composite measures are appropriate for evaluating treatment efficacy on multiple disease domains in PsA.

Trial registration: OPAL Broaden: ClinicalTrials.gov Identifier: NCT01877668 , first posted June 12, 2013; OPAL Beyond: ClinicalTrials.gov Identifier: NCT01882439 , first posted June 20, 2013.

Keywords: Assessment; CPDAI; DAPSA; DAS28–3(CRP); PASDAS; Psoriatic arthritis.

Conflict of interest statement

Ethics approval and consent to participate

Studies were conducted in accordance with the International Conference on Harmonisation and Declaration of Helsinki. Study protocols and documentation were approved by the institutional review board or independent ethics committee at each investigational site.

Consent for publication

Not applicable.

Competing interests

PH has received research grants from AbbVie, Janssen, and Pfizer Inc and has received personal fees from AbbVie, Amgen, Janssen, Pfizer Inc, and UCB. LCC has received research grants from AbbVie, Celgene, Janssen, Novartis, and Pfizer Inc and has received personal fees from AbbVie, Amgen, BMS, Celgene, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer Inc, Prothena, and UCB. OF has received grants from AbbVie, BMS, and Pfizer Inc and has received personal fees from BMS, Celgene, Janssen, Novartis, Pfizer Inc, and UCB. PN has received grants or fees for participating as a speaker or in advisory boards from AbbVie, BMS, Janssen, Lilly, MSD, Novartis, Pfizer Inc, Roche, Sanofi, and UCB. ERS has received grants or personal fees for participating as speaker or in advisory boards from AbbVie, BMS, GlaxoSmithKline, Janssen, Lilly, Novartis, Pfizer Inc, Roche, Sandoz, and UCB. MEH has received consultant or personal fees for participating in advisory boards from AbbVie, Genzyme/Sanofi, Janssen, Lilly, Novartis, and UCB. MAH, KSK, TH, JW, and EK are employees of Pfizer Inc and hold stock/stock options in Pfizer Inc.

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Figures

Fig. 1

LS mean change from baseline in (a) PASDAS, (b) DAPSA, and (c) CPDAI. For complete data, see Additional file 1: Table S1. *P ≤0.05, **P <0.01, ***P <0.001 versus placebo. Abbreviations: BID twice daily, CPDAI Composite Psoriatic Disease Activity Index, DAPSA Disease Activity Index for Psoriatic Arthritis, LS least squares, OPAL Oral Psoriatic Arthritis triaL, PASDAS Psoriatic Arthritis Disease Activity Score, Q2W once every 2 weeks, SC subcutaneous, SE standard error

Fig. 2

PASDAS response rates for patients with baseline PASDAS >3.2 (FAS). *P≤0.05, ***P<0.001 versus placebo. PASDAS response was defined as the percentage of patients who had a PASDAS score ≤3.2 and a decrease from baseline in PASDAS score ≥1.6 at the relevant time point. A missing PASDAS response at a given time point was imputed as non-response. Abbreviations: BID twice daily, FAS full analysis set, N number of patients with baseline PASDAS >3.2 in the FAS, OPAL Oral Psoriatic Arthritis triaL, PASDAS Psoriatic Arthritis Disease Activity Score, Q2W once every 2 weeks, SC subcutaneous, SE standard error

Fig. 3

Change from baseline in composite endpoint scores by MDA response status across studies, a PASDAS, b DAPSA, c CPDAI, d DAS28-3 (CRP). For complete data, see Additional file 2: Table S2. MDA response was defined as five of the following seven criteria being met: TJC ≤1, SJC ≤1, Psoriasis Area and Severity Index score ≤1 or psoriasis BSA ≤3%, patient arthritis pain (VAS) ≤15 mm, patient’s global assessment of arthritis (VAS) ≤20 mm, HAQ-DI ≤0.5, tender entheseal points (using LEI) ≤1. Abbreviations: BID twice daily, BSA body surface area, CPDAI Composite Psoriatic Disease Activity Index, DAPSA Disease Activity Index for Psoriatic Arthritis, DAS28–3(CRP) 3-component Disease Activity Score using 28 joints with C-reactive protein, FAS full analysis set, HAQ-DI Health Assessment Questionnaire-Disability Index, LEI Leeds Enthesitis Index, MDA minimal disease activity, OPAL Oral Psoriatic Arthritis triaL, PASDAS Psoriatic Arthritis Disease Activity Score, Q2W once every 2 weeks, SC subcutaneous, SJC swollen joint count, TJC tender joint count, VAS visual analog scale