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MADRID—Tofacitinib (a JAK inhibitor) used with methotrexate (MTX) is not inferior to adalimumab (a TNF inhibitor) plus MTX in rheumatoid arthritis (RA) patients who’ve had an inadequate response to MTX alone, according to results of a Phase 3B/4 trial presented in a session at the Annual European Congress of Rheumatology (EULAR).
The findings came in a one-year trial, called the ORAL Strategy, with three active treatment arms, meant to compare tofacitinib alone with tofacitinib plus MTX, tofacinitib alone with adalimumab plus MTX, and tofacitinib plus MTX with adalimumab plus MTX (see Table 1, below).1
Table 1: ORAL Strategy
| Enrollment: | 1132 |
| Study Start Date: | August 2014 |
| Study Completion Date: | December 2016 |
| Primary Completion Date: | December 2016 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
| Experimental: Tofacitinib 5 mg twice daily with methotrexate | Drug: Tofacitinib with methotrexate Tofacitinib 5 mg twice daily, oral for 12 months Methotrexate (previous stable dose 15–25 mg) every week, oral for 12 months Placebo for adalimumab every other week, subcutaneous for 12 months |
| Experimental: Tofacitinib 5 mg twice daily monotherapy | Drug: Tofacitinib without methotrexate Tofacitinib 5 mg twice daily, oral for 12 months Placebo for methotrexate (previous stable dose) every week, oral for 12 months Placebo for adalimumab every other week, subcutaneous for 12 months |
| Active Comparator: Adalimumab with methotrexate | Biological: Adalimumab with methotrexate; Placebo for tofacitinib twice daily, oral for 12 months Methotrexate (previous stable dose 15–25 mg) every week, oral for 12 months Adalimumab 40 mg every other week, subcutaneous for 12 months |
Source: ClinicalTrials.gov, NCT02187055
In the other comparisons, performed using an efficacy threshold derived from a meta-analysis of adalimumab trials, tofacitinib alone landed in a kind of statistical limbo when compared with adalimumab plus MTX: It wasn’t shown to be worse, nor was it shown to be superior. The same was found for tofacitinib alone compared with tofacitinib plus MTX.
The main point of the trial was to settle remaining questions from tofacitinib’s Phase 3 trial, which suggested that perhaps tofacitinib alone was better than tofacitinib with MTX—which was found not to be true in this trial—and that tofacitinib with MTX was better than adalimumab.
The Trial
One thousand one hundred and forty-six patients were randomized: 384 were treated with 5 mg tofacitinib monotherapy orally twice a day, 5 mg tofacitinib twice a day plus MTX or adalimumab plus MTX.
There was no significant difference between the groups, with 46% of the tofacitinib plus MTX patients achieving an ACR50 response after six months, compared with 43.8% of adalimumab plus MTX patients and 38.3% of the tofacitinib-alone patients. In a subsequent analysis, tofacitinib plus MTX was not found to be superior to adalimumab plus MTX.