Phase III results support tofacitinib for psoriatic arthritis
medwireNews: Results of two phase III trials published in The New England Journal of Medicine suggest that the Janus kinase (JAK) inhibitor tofacitinib could be a promising treatment option for different populations of patients with psoriatic arthritis (PsA).
In the OPAL Broaden study, reported previously at the EULAR 2017 meeting, Philip Mease (Seattle Rheumatology Associates, Washington, USA) and colleagues demonstrated that tofacitinib had superior efficacy to placebo among PsA patients who had previously experienced an inadequate response to conventional DMARD treatment.
The second study, OPAL Beyond, extended these results, finding that tofacitinib was also beneficial in patients with active PsA and an inadequate response to treatment with one or more tumor necrosis factor inhibitors, which are given when conventional DMARDs are ineffective.
Dafna Gladman (Toronto Western Hospital, Ontario, Canada) and co-investigators randomly assigned patients to receive treatment with oral tofacitinib at a dose of 5 or 10 mg twice daily for 6 months, or to receive placebo for 3 months followed by tofacitinib 5 mg or 10 mg until month 6.
At the 3-month follow-up, 50% of 131 participants receiving tofacitinib 5 mg and 47% of 132 patients in the tofacitinib 10 mg group achieved at least a 20% improvement in ACR criteria (ACR20) from baseline, compared with 24% of 131 patients receiving placebo, a significant difference.
Patients in the tofacitinib 5 mg and 10 mg groups also experienced significantly greater improvements in Health Assessment Questionnaire–Disability Index scores from baseline to month 3 than those given placebo, with corresponding decreases of 0.39 and 0.35 versus 0.14 points.
When skin responses were analyzed, a significantly greater proportion of participants receiving the 10 mg dose of tofacitinib versus placebo had an improvement in Psoriasis Area and Severity Index scores of at least 75% (PASI75) at month 3 (43 vs 14%). However, the 5 mg dose of tofacitinib was not superior to placebo in terms of PASI75 response rates.
Patients receiving tofacitinib 5 mg or 10 mg compared with placebo were more likely to experience adverse events (AEs) during the first 3 months of the study, with rates of 55%, 53%, and 44%, respectively. Serious AEs were reported in a corresponding 1%, 2%, and 2% of participants.
Over the full 6-month study period, 71% of patients receiving tofacitinib 5 mg and 73% of those receiving the 10 mg dose throughout the study experienced AEs. Among those who switched from placebo to tofacitinib 5 mg or 10 mg at month 3, AEs occurred in a respective 61% and 58% of patients.
Three patients receiving tofacitinib and none in the placebo groups developed nonserious herpes zoster infections throughout the study, one of which was adjudicated as an opportunistic infection.
“Although all biologic DMARDs and tofacitinib are broadly immunosuppressive, tofacitinib appears to carry an additional risk of herpes zoster infection,” say Robert Colbert and Michael Ward (National Institutes of Health, Bethesda, Maryland, USA) in an accompanying editorial, noting that differences in safety profiles will help to guide the choice of PsA treatment.
And they believe that taken together, the results of the OPAL Broaden and OPAL Beyond studies suggest that tofacitinib “has a place in the arsenal of drugs for the treatment of psoriatic arthritis.”
Looking to the future, the editorialists call for comparisons of tofacitinib with other biologic treatments to inform the place of the JAK inhibitor in the PsA treatment algorithm.
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