ORAL-Shift: Tofacitinib noninferior to combination with methotrexate in RA
Patients with rheumatoid arthritis treated with tofacitinib experienced efficacy and safety outcomes comparable to patients treated with tofacitinib plus methotrexate, according to findings presented at the EULAR Annual Congress.
“The results of ORAL Shift provide important information on the use of [tofacitinib (Xeljanz XR, Pfizer)] as monotherapy after methotrexate withdrawal, which is significant as some people living with rheumatoid arthritis are unable or unwilling to use methotrexate,” Stanley B. Cohen, MD, of the Metroplex Clinical Research Center in Dallas, said in a press release.
Cohen and colleagues compared the efficacy and safety of a tofacitinib extended-release dose of 11 mg with or without methotrexate.
The phase 3b/4 study included patients who reached low disease activity (LDA) after 24 weeks of treatment with tofacitinib plus methotrexate. These patients were randomly assigned to a second 24-week treatment methotrexate withdrawal phase, in which patients were randomly assigned 1:1 to receive tofacitinib monotherapy or tofacitinib with continued methotrexate.
Change in DAS28-ESR served as the primary outcome measure, with noninferiority of tofacitinib monotherapy to combination therapy as the endpoint. The researchers also measured HAQ-DI response, ACR20/50/70 and Clinical Disease Activity Index (CDAI)-defined LDA.
Results showed a least squares mean change in DAS28-4(ESR) of 0.33 for the monotherapy group and 0.03 for tofacitinib plus methotrexate (mean difference = 0.3; 95% CI, 0.12-0.48) at week 48, demonstrating noninferiority, according to the researchers.
Additional findings showed a non-clinically meaningful benefit for tofacitinib monotherapy in outcomes including change in DAS28-4(CRP), SDAI and CDAI, according to the results. Comparable outcomes were reported between the two arms in terms of ACR and HAQ-DI responses, along with LDA rates. Both treatment regimens yielded similar remission rates.
The safety profile showed 10 serious adverse events and five discontinuations due to adverse events overall in the monotherapy group. The combination therapy yielded five serious adverse events and five discontinuations due to adverse events.
During the double-blind phase of the trial, 40.5% of patients in the monotherapy arm experienced adverse events, compared to 41% in the methotrexate group. The serious adverse event rates were 3.8% of patients in the monotherapy arm and 1.9% of those in the combination therapy arm.
“From a clinical perspective, these results give physicians data to help inform the decision to take appropriate patients off methotrexate,” Cohen said. – by Rob Volansky
Cohen SB, et al. LB0002. Presented at: EULAR Annual Congress; June 12-15, 2019; Madrid.
Disclosure: Cohen reports receiving grant or research support from and consulting for AbbVie, Eli Lilly, Genentech, Gilead and Pfizer.