Tofacitinib Monotherapy Offers Significant Benefits for Active RA

San Diego—In patients with rheumatoid arthritis (RA), tofacitinib monotherapy significantly inhibits progression of structural damage, improves signs and symptoms of disease, and improves function over 2 years compared to patients treated with methotrexate monotherapy, according to a study presented during a poster session at the ACR/ARHP meeting.

This was a phase 3, international, multicenter, double-blind, parallel group study that compared the efficacy and safety of tofacitinib monotherapy with methotrexate monotherapy in methotrexate-naïve patients with active RA.

Lead investigator, Roy M. Fleischman, MD, Metroplex Clinical Research Center, Dallas, Texas, and colleagues randomized 956 patients to receive tofacitinib 5 mg twice daily (n=373), tofacitinib 10 mg twice daily (n=397), or methotrexate 10 mg/week with 5 mg/week increments every 4 weeks to 20 mg/week, for a mean methotrexate dose of 18.5 mg/week at the end of the 3 month titration (n=186).

All patients in the study were >18 years of age, had no prior treatment with methotrexate, had active RA as defined by the American College of Rheumatology (ACR) 1987 revised criteria, and had >3 joint erosions and/or were rheumatoid factor-positive and/or anti-cyclic citrullinated peptide-positive.

The primary end points at 6 months were mean change from baseline in van der Heijde modified total Sharp score (mTSS) and ACR70 response rate. Key secondary end points included mTSS at 12 and 24 months; erosion and joint space narrowing scores at 6, 12, and 24 months; ACR20, ACR50, and ACR70 response rates at all visits; proportion of patients achieving disease activity score 28-4 (DAS28; ie, DAS-defined remission as DAS28<2.6); low disease activity (ie, DAS28 <3.2) at all visits; and Health Assessment Questionnaire-Disability Index (HAQ-DI) at all visits.

At 24-months, the study found that the mean changes from baseline in mTSS and ACR20/50/70 response rates were all significantly superior in patients treated with either dose of tofacitinib monotherapy compared to methotrexate monotherapy.

Patients treated with tofacitinib 5 mg twice daily and tofacitinib 10 mg twice daily, compared to those treated with methotrexate monotherapy, had significantly superior clinical outcomes as indicated by significantly superior ACR70 response (34.4% and 37.6% vs 15.2%, respectively; P<.0001), least squares (LS) mean change from baseline in DAS28-4 (-2.99 and -3.16 vs -2.40, respectively; P=<.0001), rate of DAS28-4<2.6 (20.8% and 22.3% vs 9.94%, respectively; P<.001 and P<.0001, respectively), and rate of DAS28-4<3.2 (34.8% and 36.0% vs 15.8%, respectively; P<.0001).

Tofacitinib at 5 mg and 10 mg was also significantly superior to methotrexate monotherapy in functional scores, as indicated by differences in the LS mean change from baseline in HAQ-DI (-0.90 and -1.01 versus -0.70, respectively; P<.001 and P<.0001, respectively), as well as radiographic measurements as indicated by LS mean change from baseline in mTSS (0.55 and 0.28 vs 2.08, respectively; P<.001 and P<.0001, respectively) and LS mean change from baseline in erosion score (0.16 and 0.16 vs 0.98, respectively; P<.0001).

In terms of safety, higher rates of herpes zoster infections occurred at a higher incidence with tofacitinib compared to methotrexate. Tofacitinib was also associated with decreases in neutrophil and lymphocyte counts, as well as increases in creatinine and lipid levels. Patients treated with methotrexate had higher incidence of gastrointestinal disorders and higher, albeit infrequent, incidence of transaminase elevations >3x upper limit of normal. Overall, the study reported 6 malignancies and 4 deaths.