Study Populations and Design
MCIDs for the presenteeism, work productivity loss, and activity impairment domains of WPAI:SHP were derived separately using the intent-to-treat populations of SPIRIT-P1 and SPIRIT-P2. These studies and their patient populations were previously described by Mease and colleagues  and Nash and colleagues . SPIRIT-P1 and SPIRIT-P2 were multicenter, randomized, double-blind, placebo-controlled phase 3 trials. SPIRIT-P1 enrolled biologic-naïve patients. SPIRIT-P2 enrolled tumor necrosis factor inhibitor (TNFi)-experienced patients who were either inadequate responders or intolerant to TNFi therapies. Patients participating in the trials were 18 years or older, diagnosed with active PsA at least 6 months prior, met the classification criteria for psoriatic arthritis (CASPAR) criteria (at least 3/68 tender and 3/66 swollen joints), and had either a documented history of plaque psoriasis or active psoriatic skin lesions. Patients participating in SPIRIT-P1 were randomized 1:1:1:1 to receive placebo, 80 mg ixekizumab every 4 weeks (IXEQ4W), 80 mg ixekizumab every 2 weeks (IXEQ2W), or 40 mg adalimumab every 2 weeks. Patients participating in SPIRIT-P2 were randomized 1:1:1 to receive placebo, IXEQ4W, or IXEQ2W. Patients receiving ixekizumab received a 160-mg starting dose in both trials. Adalimumab was included as the active-reference arm in SPIRIT-P1. Both SPIRIT-P1 and SPIRIT-P2 were conducted in accordance with the ethical principles of the Declaration of Helsinki and in compliance with local laws and regulations. All participants provided informed consent. SPIRIT-P1 and SPIRIT-P2 protocols and consent forms were approved by each site’s institutional review board or ethics committee, including the Western Institutional Review Board for SPIRIT-P1 and the Bellberry Human Research Ethics Committee for SPIRIT-P2. The individual SPIRIT-P1 and SPIRIT-P2 sites are listed in the primary manuscript supplements [13, 14]. Both studies were registered on ClinicalTrials.gov (SPIRIT-P1: NCT01695239, SPIRIT-P2: NCT02349295).
WPAI:SHP  (V2.0) was administered during the double-blind treatment period (weeks 0–24) at prespecified time points, and continued in the extension periods. In the questionnaire template, “PROBLEM” was replaced with “psoriatic arthritis.” The questionnaire consisted of six questions assessing employment status, hours missed from work due to PsA, hours missed from work due to other reasons, actual hours worked, the impact of PsA on work productivity, and the impact of PsA on activities outside of work. The responses to these questions were used to derive four scores: percentage of absenteeism, percentage of presenteeism, work productivity loss (incorporates absenteeism and presenteeism), and the percentage of activity impairment outside of work. Higher scores indicate a higher degree of impairment.
MCIDs for the presenteeism, work productivity loss, and activity impairment domains of WPAI:SHP through week 24 were derived using the anchor-based method supplemented by the distribution-based method in accordance with FDA guidance  and Copay et al. . The patient populations of SPIRIT-P1 and SPIRIT-P2 were individually pooled and kept separate for all analyses. Anchor variables included the American College of Rheumatology (ACR) 20/50/70 responder indices, the minimal disease activity (MDA) , and the Health Assessment Questionnaire Disability Index (HAQ-DI) MCID (improvement ≥ 0.35) . Efficacy results for ACR20 [13, 14], ACR50 [13, 14], ACR70 [13, 14], MDA [14, 18], and HAQ-DI MCID [13, 14] were previously published. Per FDA guidance , a valid anchor is expected to be understandable, interpretable, and adequately associated with the WPAI:SHP instrument. ACR20/50/70, MDA, and HAQ-DI were considered to be understood and interpretable by rheumatologists for the purposes of these analyses. To validate our anchor choices in preparation for anchor-based analyses, we evaluated associations between WPAI:SHP domain scores and anchors using biserial correlation, logistic modeling, and analysis of covariance (ANCOVA). A threshold of 0.371 signified a large effect for the biserial correlation analysis . The concordance index (ranging from 0.5 to 1.0) from a logistic model is another metric that was used to quantify the association between anchor and WPAI:SHP domains. The larger the concordance index, the stronger the association. The ANCOVA models were employed to demonstrate a significantly greater improvement in the WPAI:SHP domains among patients who met the anchor than among those who did not meet the anchor. For the anchor-based method, we utilized the receiver operating characteristic (ROC) method to identify cutoffs for each WPAI:SHP domain that best differentiated each anchor. When a cutoff is set too low, we would expect to observe a high sensitivity and a negative predictive value. On the other hand, when a cutoff is set too high, both the sensitivity and the negative prediction value decrease while the specificity and positive predictive value increase. An ideal cutoff should balance the tradeoff while being greater than the half the standard deviation or SEM recommended by the distribution-based method. The distribution method used measures of instrument variability, including the standard error of measurement with an assessment of the reliability coefficient with a lower bound of 0.7, as reported by Crawford and colleagues , and multiplying by half of the standard deviation . The results of the anchor- and distribution-based method were used to triangulate MCIDs for the domains of WPAI:SHP . Analyses were performed using SAS (version 9.4).