The following article is a part of conference coverage from the 2019 American College of Rheumatology/Association of Rheumatology Professionals (ACR/ARP) Annual Meeting, being held in Atlanta, Georgia. The team at Rheumatology Advisor will be reporting on the latest news and research conducted by leading experts in rheumatology. Check back for more from the 2019 ACR/ARP Annual Meeting.
ATLANTA — Selective interleukin-1 receptor associated kinase 4 (IRAK4) inhibitor may reduce clinical disease scores in patients with moderate to severe rheumatoid arthritis (RA), according to study results presented at the 2019 American College of Rheumatology/Association of Rheumatology Professionals (ACR/ARP) Annual Meeting, held November 8 to 13, 2019, in Atlanta, Georgia.
Investigators conducted a phase 2b, multicenter, double-blind, randomized clinical trial of PF-06650833 (ClinicalTrials.gov Identifier: NCT02996500), a selective, reversible IRAK4 inhibitor, for the treatment of RA. Patients with moderately to severely active RA and inadequate response to methotrexate were randomly assigned (6:6:6:5:5:5) to receive 12 weeks of PF-06650833 20 mg, 60 mg, 200 mg, or 400 mg modified-release tablets once daily; tofacitinib 5 mg twice daily; or placebo. The primary end point was change from baseline to week 12 in simplified disease activity index (SDAI) score. Investigators also evaluated change from baseline in Disease Activity Score 28 with 4 components-C-reactive protein (DAS28-4[CRP]) at week 12. In addition, secondary end points included the percentage of patients achieving improvement in American College of Rheumatology (ACR) 20, 50, and 70 scores. Adverse events (AEs) were monitored throughout the trial.
A total of 269 patients from 19 countries were randomly assigned to receive either PF-06650833 (n=187), tofacitinib (n=43), or placebo (n=39). Mean change from baseline to week 12 in SDAI score was significantly higher in the PF-06650833 group compared with the placebo group (P ≤.005) using a primary Bayesian analysis with an informative placebo before distribution. Compared with placebo, a greater percentage of patients receiving PF-06650833 200 mg (40.0%; P =.040) and 400 mg (43.8%; P =.016) achieved ACR50 response rates at week 12. Significant change from baseline in DAS28-4(CRP) was observed in the PF-06650833 60 mg, 200 mg, and 400 mg groups vs placebo (P <.05). A total of 222 AEs were reported during the trial, of which 64 were treatment-related and 8 were serious. Treatment-related AEs were not dose-dependent. The most common AEs were system organ class infections and infestations (20.4%; n=55); 3 patients developed herpes zoster, and 12 patients permanently discontinued treatment due to adverse events. No deaths were reported.
All dosing regimens of PF-06650833 were associated with improvements in clinical disease activity in patients with RA. Safety signals were assessed, with infections and infestations most commonly observed. PF-06650833 requires further study to identify the most effective dosing regimen and elucidate all safety signals.
Disclosure: This clinical trial was supported by Pfizer, Inc. Please see the original reference for a full list of authors’ disclosures.
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Danto SI, Shojaee N, Singh RSP, et al. Efficacy and safety of the selective interleukin-1 receptor associated kinase 4 inhibitor, PF-06650833, in patients with active rheumatoid arthritis and inadequate response to methotrexate. Presented at: 2019 ACR/ARP Annual Meeting; November 8-13, 2019; Atlanta, GA. Abstract 2909.