Vinod Chandran, MBBS, MD, DM, PhD
Although PsA affects men and women equally, the impact of the disease is often worse in women. In a large study from the Netherlands , in which 855 patients were carefully evaluated and follow up, Mulder MLM et al show that both subjective and objective measures of disease activity is more severe in women than men. The PsA Disease Activity Score, a validated composite measure of PsA disease activity, was also higher in women than men. The impact of disease on quality of life and function was significantly more in women and they were less often meeting treatment target. Further research into the impact of sex and gender in PsA is warranted and sex/gender-specific measures for managing PsA is required.
Janus kinase inhibitors (JAKi) are important new molecules increasingly being used in the management of inflammatory diseases. Tofacitinib is already available for the treatment of PsA. McInnes IB et al published results on the efficacy of u padacitinib, a more selective JAK1i already approved for treatment of RA, in treating PsA. In this phase 3 trial involving 1,704 patients with PsA who had an inadequate response to at least 1 nonbiologic disease-modifying antirheumatic drugs, the p roportion of patients achieving at least 20% improvement in American College of Rheumatology (ACR20) response was significantly higher with upadacitinib 15 mg (70.6%) and 30 mg (78.5%) than with placebo (36.2%; P less than .001). Upadacitinib 15mg was found to have comparable efficacy as adalimumab (ACR20 65.0%), a well-established anti-TNF agent. However, adverse events were more frequent with upadacitinib.
Adverse events when on treatment with JAKi have recently come into sharp focus. Reassuringly, results from the OPAL Balance study , a 36-month, long-term extension phase 3 study involving 686 adult patients with active PsA on treatment with tofacitinib confirmed the long-term safety and efficacy of tofacitinib in patients with PsA. Nash P et al reported 1 instance of mortality occurred in tofacitinib group during the risk period (incidence, 0.1 patients with events [95% confidence interval, 0.0-0.3] per 100 person-years). The incidences of adverse events for herpes zoster, serious infections, opportunistic infections, adjudicated malignancies, and major adverse cardiovascular events were consistent with previous reports. However, given the reports of higher adverse events with tofacitinib compared to anti-TNF drugs in high-risk rheumatoid arthritis patients, more data is required to fully understand the risk profile of JAKi in patients with immune-mediated inflammatory diseases, including PsA.
With several drugs currently available to treat PsA and the paucity of head-to-head trials between them, choosing the most efficacious drug for treating patients with PsA has become challenging. To address this issue a network meta-analysis of 26 phase 3, randomized controlled trials that evaluated 13 targeted therapies among adults with active PsA was conducted. In a study sponsored by Janssen, Mease PJ et al report that g uselkumab 100 mg every 8 weeks and every 4 weeks were comparable to anti IL-17A and subcutaneous anti-TNF agents for achieving ACR20 response. Guselkumab showed better Psoriasis Area Severity Index 90 and 75 responses than most of the other agents. The results indicate that guselkumab is as effective as other established agents in treating PsA, but formal head-to-head clinical trials will provide better evidence of relative efficacy and safety.