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

Philip Helliwell,Laura C Coates,Enrique R Soriano,Elizabeth Kudlacz,Ming-Ann Hsu,Oliver Fitzgerald,Joseph Wu,Thijs Hendrikx,Keith S Kanik,Peter Nash,M Elaine Husni

doi:10.1186/s13075-018-1739-0

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.

Highlights

The multiple disease domains affected in psoriatic arthritis (PsA) may make composite endpoints appropriate for assessing changes in disease activity over time
Tofacitinib had greater efficacy than placebo on the basis of the primary endpoints: a higher proportion of patients receiving tofacitinib than placebo achieved greater than or equal to 20% improvement according to the criteria of the American College of Rheumatology (ACR20 response) at month 3, and the mean change from baseline to month 3 in Health Assessment Questionnaire-Disability Index (HAQ-DI) score was greater in patients receiving tofacitinib versus placebo at month 3
Following advancement from placebo to tofacitinib treatments at month 3, patients showed similar improvements in disease activity at month 6 to those observed in patients receiving tofacitinib 5 or 10 mg Twice daily (BID) throughout (Additional file 1: Table S1 and Fig. 1a); this improvement was maintained until the end of the 12-month Oral Psoriatic Arthritis triaL (OPAL) Broaden study (Table 2 and Fig. 1a) and was larger in patients in the placebo advancing to tofacitinib 10 mg BID group than the placebo advancing to tofacitinib 5 mg BID group

Summary

Introduction

The multiple disease domains affected in psoriatic arthritis (PsA) may make composite endpoints appropriate for assessing changes in disease activity over time. Owing to the multiple diverse disease manifestations involved in PsA, the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) bases its treatment recommendations on the domains affecting an individual [1]. Composite endpoints, which allow the assessment of multiple clinical outcomes in a single instrument, have been suggested to be useful to assess changes in the multiple disease domains of PsA over time [3, 4]. A number of composite endpoints have been developed for PsA in order to assess multiple aspects of disease activity and identify patients who have achieved treatment targets of remission or minimal disease activity (MDA). There is no clear agreement on a standardized composite assessment approach that provides the optimal combination of individual variables [6], agreement has been reached on a core domain set of variables that should be included [7]

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Results

Discussion

Conclusion