ORAL Shift Phase IIIb/IV study of Xeljanz XR shows efficacy in rheumatoid arthritis

Pfizer Inc. announced positive results from ORAL Shift, a Phase IIIb/IV study in adult patients with moderately to severely active rheumatoid arthritis (RA). Patients who achieved low disease activity (LDA) with Xeljanz (tofacitinib) extended release (XR) 11 mg once daily (QD) plus methotrexate (MTX) after a 24-week open-label run-in period, were randomized to evaluate the efficacy and safety of Xeljanz XR 11 mg QD as monotherapy after MTX withdrawal compared with Xeljanz XR with continued MTX.

The study demonstrated non-inferiority of MTX withdrawal with Xeljanz XR 11 mg QD compared to Xeljanz XR 11 mg QD plus MTX at week 48 as measured by the primary endpoint, the change in the Disease Activity Score (DAS28-4[ESR]) from randomization at week 24 to the end of the double-blind MTX withdrawal phase at week 48. For the primary efficacy analysis, patients who achieved Clinical Disease Activity Index (CDAI) low disease activity at week 24 were randomized into the MTX withdrawal phase resulting in least squares (LS) mean changes in DAS28-4(ESR) from weeks 24 to 48 of 0.33 and 0.03 in the Xeljanz XR monotherapy and Xeljanz XR plus MTX groups, respectively [LS mean difference = 0.3; 95% CI, 0.12-0.48; non-inferiority p.

The safety findings in ORAL Shift include the most frequently reported adverse events (AEs) for each study group in the double-blind treatment period of nasopharyngitis, upper respiratory tract infection and bronchitis. Rates of AEs, serious AEs (SAEs) and discontinuations due to AEs were generally comparable between treatment arms. In the Xeljanz XR monotherapy group, there were 10 SAEs and 5 discontinuations due to AEs. In the Xeljanz XR plus MTX group, there were 5 SAEs and 5 discontinuations due to AEs. During the double-blind withdrawal phase of the study, AEs were reported in 40.5% of patients (n=107) in the Xeljanz XR monotherapy treatment group and 41.0% of patients (n=109) in the Xeljanz XR plus MTX treatment group.

In addition, SAEs were reported in 3.8% of patients (n=10) in the Xeljanz XR monotherapy treatment group and 1.9% of patients (n=5) in the Xeljanz XR plus MTX treatment group. In the double-blind treatment period, there were two deaths reported in the Xeljanz XR plus MTX treatment group. The study results will be presented during a late-breaking oral session at the Annual European Congress of Rheumatology (EULAR 2019) in Madrid, Spain (15 June).