Dose-Dependent ACR20 Response Rates in RA With Peficitinib
JAK inhibitors block the activity of an array of inflammatory cytokines implicated in the pathogenesis of RA.
Use of the Janus kinase (JAK) inhibitor peficitinib in combination with certain conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) results in a dose-dependent ACR20 (the percentage of patients meeting the American College of Rheumatology 20% improvement criteria) response rate in patients with rheumatoid arthritis (RA) over 12 weeks, according to results from a recent phase 2b dose-finding study published in Arthritis & Rheumatology.1
JAK inhibitors block the activity of an array of inflammatory cytokines implicated in the pathogenesis of RA.2 Peficitinib is among several JAK inhibitors currently being tested for RA. Other JAK inhibitors currently in development include baricitinib, filgotinib, and ABT-494.
Study co-investigator Alan J. Kivitz, MD, CPI, noted that despite the availability of numerous therapies for RA, new agents are still needed. “If one looks at the response rates for existing therapies, we might be content with an ACR20 of 70% to 80%, an ACR50 of 40%, and an ACR70 of 20%. But looked at conversely, that still means that large numbers of patients for any particular therapy are not getting the optimal improvement.” ACR20, ACR50, and ACR70 represent improvements in tender or swollen joint counts and other disease activity measures ≥20%, 50%, and 70%, respectively.
In order to evaluate the efficacy, safety, and dose response of once-daily oral peficitinib over 12 weeks in patients with moderate to severe RA who had not responded to treatment with csDMARDs, the investigators randomly assigned 289 patients at 41 sites in 6 countries to receive peficitinib 25 mg (n=59), peficitinib 50 mg (n=57), peficitinib 100 mg (n=58), peficitinib 150 mg (n=64), or placebo (n=51). Patients were allowed to continue to take anti-inflammatory drugs, specific csDMARDs (hydroxychloroquine, chloroquine, or sulfasalazine), and/or oral corticosteroids.
Results showed that 22.0%, 36.8%, 48.3%, 56.3%, and 29.4% of patients who received peficitinib 25 mg, 50 mg, 100 mg, 150 mg, and placebo, respectively, achieved an ACR20 response, the study's primary end point. These results were statistically significant compared with placebo only for the 100 mg peficitinib (P <.05) and 150 mg peficitinib (P <.01). Statistically significant differences for the peficitinib 100 mg and 150 mg groups vs placebo were also found for secondary end points of ACR50 response and change from baseline DAS28-CRP (Disease activity score in 28 joints using the C-reactive protein level). No significant difference in adverse events was noted in the peficitinib or placebo groups.
Summary & Clinical Applicability
“To fully assess the efficacy and safety of this novel JAK inhibitor, longer-term and larger-scale phase III studies of peficitinib 100 mg and 150 mg are currently ongoing (ClinicalTrials.gov Identifiers NCT02308163 and NCT02305849),” wrote the investigators. “In conclusion, orally administered once daily peficitinib without concomitant use of [methotrexate] reduced the symptoms of RA, and a dose-dependent response was observed in the ACR20 and ACR50 response rates as well as in the change from baseline DAS28-CRP,” wrote the researchers.
Limitations & Disclosures
- The study duration was short (12 weeks)
- The patient population examined was small (289)
- Concomitant use of hydroxychloroquine, chloroquine, and sulfasalazine was required by regulators, thus precluding the examination of true peficitinib monotherapy
Astellas Pharma Global Development was involved in the study design and in the collection, analysis, and interpretation of the data.
- Genovese MC, Greenwald M, Codding C, et al. Peficitinib, a JAK inhibitor, in combination with limited conventional synthetic disease-modifying antirheumatic drugs in the treatment of moderate-to-severe rheumatoid arthritis. Arthritis Rheumatol Hoboken NJ. 2017;69:932-942. doi:10.1002/art.40054
- Banerjee S, Biehl A, Gadina M, Hasni S, Schwartz DM. JAK–STAT signaling as a target for inflammatory and autoimmune diseases: current and future prospects. Drugs. 2017;77:521-546. doi:10.1007/s40265-017-0701-9