Tofacitinib plus MTX found noninferior to adalimumab plus MTX

In patients with rheumatoid arthritis, a regimen of tofacitinib given 5 mg twice daily plus methotrexate delivered efficacy similar to that of adalimumab plus methotrexate, according to a study presented at the 2017 EULAR Annual Congress.

“ORAL Strategy is a phase 3b/4, double-blind, head-to-head noninferiority study that compared the efficacy and safety of Xeljanz [tofacitinib, Pfizer] 5 mg twice daily as both monotherapy and in combination with [methotrexate] MTX to Humira [adalimumab, AbbVie] 40 mg every other week with methotrexate,” researcher Roy Fleischmann, MD, told Healio Rheumatology. “It also compared the efficacy and safety of Xeljanz monotherapy with Xeljanz in combination with methotrexate.”

Roy Fleischmann

Researchers evaluated 1,146 patients with active rheumatoid arthritis, defined as at least four tender/painful joints on motion and at least four swollen joints at baseline, insufficiently controlled with MTX. They randomly assigned patients at a 1:1:1 ratio to undergo treatment with one of the following regimens: tofacitinib 5-mg BID (n=384); tofacitinib 5-mg BID plus MTX (n=376); or subcutaneous adalimumab (ADA) 40 mg every other week plus MTX 15 mg to 25 mg/week (n=386). Most patients were female and white. The mean age was 49.7±50.7 years. The median disease duration was 5.4 to 6.1 years and the mean health assessment disability index score was 1.6.

The primary endpoint was ACR50 at 6 months. The tofacitinib regimens would be considered noninferior to the ADA plus MTX treatment if the lower bound of 98.34% two-sided confidence intervals of the difference in 6-month ACR50 response was larger than -13% (based on meta-analysis of ADA trials). Superiority was established if the difference was larger than 0%. Safety was evaluated throughout the duration of the trial. The study was completed by 80.2% to 82.6% across groups.

At 6 months, the following ACR50 response rates were observed in the groups: 38.3% for 5 mg mono BID; 46.0% for 5-mg BID-MTX; and 43.8% for ADA plus MTX. The 5-mg BID-MTX was found to be noninferior to ADA plus MTX; but 5-mg mono BID did not achieve noninferiority vs. ADA plus MTX. Moreover, 5-mg monotherapy BID was not inferior to BIX plus MTX; a numerical difference was observed in this comparison, but not a statistically different. In this patient population, tofacitinib monotherapy did achieve the efficacy expected of an effective immunomodulator. The secondary efficacy analyses were generally similar to the primary analysis. Comparable rates of adverse events (5-mg BID plus MTX, 61.4%; 5-mg BID monotherapy, 58.9%; ADA plus MTX, 65.5%) serious adverse events (5-mg BID plus MTX, 7.2%; 5-mg BID monotherapy 9.1%, and ADA plus MTX, 6.2%) and discontinuation due to adverse event rates were seen across groups. The most common adverse events for each study group were upper respiratory tract infections, alanine aminotransferase increase, nasopharyngitis, urinary tract infections and nausea.

The rate of increased alanine aminotransferase was numerically lower with 5-mg BID vs. the other two groups.

“Although Xeljanz monotherapy did not demonstrate noninferiority to either combination arm, the clinical responses observed are reflective of that in the phase 3 clinical program,” Fleischmann said, “This affirms that Xeljanz is a viable option, both in combination with MTX and as monotherapy for patients who do not respond to or are intolerant to methotrexate.” – by Jennifer Byrne

Reference:

Fleischmann R, et al. Abstract #LB0003. Presented at: EULAR Annual Congress; June 14-17, 2017; Madrid.

Disclosures: Fleischmann reports he receives grant/research support from Abbott, Amgen, Astellas, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Genentech, Eli Lilly, Janssen, Novartis, Pfizer, Regeneron Pharmaceuticals, Sanofi Aventis, Roche and UCB; and is a consultant for Abbott, Akros, Amgen, Bristol-Myers Squibb, Celgene, Genentech, Eli Lilly, Janssen, Novartis, Pfizer, Sanofi Aventis and UCB. Please see the full study for a list of the other authors’ relevant disclosures.