| Samenvatting: | <p><strong>Introduction: </strong>Pain is a multidimensional factor and core domain of psoriatic arthritis (PsA). This analysis aimed to quantify the role of potential inflammation-associated outcomes on pain reduction in patients with PsA receiving tofacitinib, using mediation modeling.</p>
<p><strong>Methods: </strong>Pooled data were from two phase 3 studies (OPAL Broaden and OPAL Beyond) of patients with active PsA treated with tofacitinib 5 mg twice daily or placebo. Mediation modeling was utilized to quantify the indirect effects (via Itch Severity Item [ISI], C-reactive protein [CRP] levels, swollen joint count [SJC], Psoriasis Area and Severity Index [PASI], and enthesitis [using Leeds Enthesitis Index]) and direct effects (representing all other factors) of tofacitinib treatment on pain improvement.</p>
<p><strong>Results: </strong>The initial model showed that tofacitinib treatment affects pain, primarily indirectly, via ISI, CRP, SJC, PASI, and enthesitis (overall 84.0%; <em>P</em> = 0.0009), with 16.0% (<em>P</em> = 0.5274) attributable to the direct effect. The model was respecified to exclude SJC and PASI. Analysis of the final model revealed that 29.5% (<em>P</em> = 0.0579) of tofacitinib treatment effect on pain was attributable to the direct effect, and 70.5% (<em>P</em> < 0.0001) was attributable to the indirect effect. ISI, CRP, and enthesitis mediated 37.4% (<em>P</em> = 0.0002), 15.3% (<em>P</em> = 0.0107), and 17.8% (<em>P</em> = 0.0157) of the tofacitinib treatment effect on pain, respectively.</p>
<p><strong>Conclusions: </strong>The majority of the effect of tofacitinib on pain was collectively mediated by itch, CRP, and enthesitis, with itch being the primary mediator of treatment effect.</p>
<p><strong>Trial Registration</strong>: NCT01877668, NCT01882439.</p>
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