Updated Phase 3 Results of Tofacitinib Therapy Trial

Washington, DC—After 2 years of treatment with tofacitinib in combination with methotrexate (MTX), patients with active rheumatoid arthritis (RA) with prior inadequate response to MTX showed reduction in progression of structural damage as well as improvement in signs and symptoms of disease activity and physical functioning, investigators reported at the ACR meeting.

The findings were presented during a poster session at the ACR meeting. The poster was titled Tofacitinib, an Oral Janus Kinase Inhibitor, in Combination with Methotrexate, Reduced the Progression of Structural Damage in Patients with Rheumatoid Arthritis: Year 2 Efficacy and Safety Results From a 24-Month Phase 3 Study.

In November, the FDA approved tofacitinib to treat adults with moderately to severely active RA who had an inadequate response to or were intolerant of methotrexate.

In the phase 3, 24-month, randomized, placebo-controlled trial, 797 patients with active RA with an inadequate response to MTX were randomized to 5 mg of tofacitinib twice daily (n=321),
10 mg of tofacitinib twice daily (n=316), placebo advanced to 5 mg of tofacitinib twice daily (n=81), or placebo advanced to 10 mg of tofacitinib twice daily (n=79). All patients included in the study were at least 18 years of age with a diagnosis of active RA based on the ACR 1987 revised criteria, and had failed to achieve adequate response to stable doses of MTX. Eligible patients also were required to have evidence of either >3 distinct joint erosions on hand and wrist or foot radiographs or a positive IgM rheumatoid factor or antibodies to cyclic citrullinated peptide.

Patients in the placebo groups who were considered nonresponders at 3 months (those who did not achieve a >20% improvement in swollen and tender joint counts at month 3) were blindly advanced to the tofacitinib dose in their randomization sequences. All patients remaining on placebo at 6 months were blindly advanced to tofacitinib 5 or 10 mg twice daily. Patients who were nonresponders in the tofacitinib 5- and 10-mg twice-daily arms at 3 months remained on the same dose of tofacitinib for the duration of the study.

The study found that tofacitinib demonstrated efficacy at 24 months based on all the measures of efficacy used in the study (ACR response, Disease Activity Score 28 based on erythrocyte sedimentation rates, as well as mean changes from baseline for the modified Total Sharp Scores).

In addition, the study found that most adverse events at 24 months were mild or moderate. The number of patients that withdrew due to adverse events related to tofacitinib included 36 (11.2%) on 5 mg twice daily, 37 (11.7%) on 10 mg twice daily, 8 (9.9%) on placebo to 5 mg twice daily, and 10 (12.7%) on placebo to 10 mg twice daily. Overall, 8 patients had 1 opportunistic infection and 4 patients (all on 5 mg twice daily) died. Of the 4 deaths, 1 was an acute myocardial infarction not considered related to tofacitinib, and the other 3 that were considered to be related to tofacitinib included cardio-respiratory arrest, cardiac failure, and congestive cardiac and renal failure.

Désirée van der Heijde, MD, the study’s lead author from the Leiden University Medical Center in Leiden, The Netherlands, said these results build on preliminary 6-month results showing that the inhibition of structural damage as well as improvements in signs and symptoms, disease activity, and physical function with tofacitinib are maintained through 24 months. Dr. van der Heijde said that the safety data are consistent with other phase 3 studies of shorter duration with no new safety signals.

This study was supported by Pfizer Inc.