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Tofacitinib for Psoriatic Arthritis in Patients with an Inadequate Response to TNF Inhibitors
Dafna Gladman1, William Rigby1, Valderilio F Azevedo1
1From the University of Toronto, Toronto Western Hospital, Toronto (D.G.); Geisel School of Medicine at Dartmouth, Dartmouth-Hitchcock Medical Center, Lebanon, NH (W.R.); Universidade Federal do Paraná, Curitiba, Brazil (V.F.A.); Goethe University and Fraunhofer Institute for Molecular Biology and Applied Ecology Project Group Translational Medicine and Pharmacology (TMP), Frankfurt, Germany (F.B.); Hospital Universitario Marqués de Valdecilla, Instituto de Investigación Marqués de Valdecilla, Santander, Spain (R.B.); Specjalistyczne Gabinety Lekarskie DERMED, Lodz, Poland (A.K.); Pfizer, Groton, CT (E.K., C.W., S.M., K.S.K.); and Pfizer, Collegeville, PA (T.H.).
Background:
Tofacitinib is an oral Janus kinase inhibitor that is under investigation for the treatment of psoriatic arthritis. We evaluated tofacitinib in patients with active psoriatic arthritis who had previously had an inadequate response to tumor necrosis factor (TNF) inhibitors.
Methods:
In this 6-month randomized, placebo-controlled, double-blind, phase 3 trial, we randomly assigned 395 patients, in a 2:2:1:1 ratio, to four regimens: 5 mg of tofacitinib administered orally twice daily (132 patients); 10 mg of tofacitinib twice daily (132 patients); placebo, with a switch to 5 mg of tofacitinib twice daily at 3 months (66 patients); or placebo, with a switch to 10 mg of tofacitinib twice daily at 3 months (65 patients). Data from the patients who received placebo during the first 3 months of the trial were pooled. The primary end points were the percentage of patients who had at least 20% improvement according to the criteria of the American College of Rheumatology (ACR20 response) and the change from baseline score on the Health Assessment Questionnaire-Disability Index (HAQ-DI; scores range from 0 to 3, with higher scores indicating greater disability) at the month 3 analysis.
Results:
At 3 months, the rates of ACR20 response were 50% with the 5-mg dose of tofacitinib and 47% with the 10-mg dose, as compared with 24% with placebo (P<0.001 for both comparisons); the corresponding mean changes from baseline in HAQ-DI score were -0.39 and -0.35, as compared with -0.14 (P<0.001 for both comparisons). Serious adverse events occurred in 4% of the patients who received the 5-mg dose of tofacitinib continuously and in 6% who received the 10-mg dose continuously. Over the course of 6 months, there were four serious infections, three herpes zoster infections, one myocardial infarction, and one ischemic stroke among the patients who received tofacitinib continuously. Elevations of aspartate and alanine aminotransferase concentrations of three or more times the upper limit of the normal range occurred in more patients who received tofacitinib continuously than in patients who received placebo followed by tofacitinib.
Conclusions:
In this trial involving patients with active psoriatic arthritis who had had an inadequate response to TNF inhibitors, tofacitinib was more effective than placebo over 3 months in reducing disease activity. Adverse events were more frequent with tofacitinib than with placebo. (Funded by Pfizer; OPAL Beyond ClinicalTrials.gov number, NCT01882439 .).
Insights
Tofacitinib effectively treated active psoriatic arthritis in patients unresponsive to TNF inhibitors, showing significant improvements in ACR20 response and HAQ-DI scores. Adverse events were more frequent with tofacitinib compared to placebo.
Area of Science:
- Rheumatology
- Immunology
- Pharmacology
Background:
- Psoriatic arthritis is a chronic inflammatory condition affecting joints and skin.
- Tumor necrosis factor (TNF) inhibitors are a common treatment, but some patients show inadequate response.
- Tofacitinib, an oral Janus kinase (JAK) inhibitor, is being investigated for psoriatic arthritis.
Purpose of the Study:
- To evaluate the efficacy and safety of tofacitinib in patients with active psoriatic arthritis.
- To assess tofacitinib's effectiveness in patients with prior inadequate response to TNF inhibitors.
Main Methods:
- A 6-month, randomized, placebo-controlled, double-blind, phase 3 trial.
- 395 patients were assigned to receive 5 mg or 10 mg of tofacitinib twice daily, or placebo with a switch to tofacitinib at 3 months.
- Primary endpoints included American College of Rheumatology 20% improvement (ACR20) and Health Assessment Questionnaire-Disability Index (HAQ-DI) change at 3 months.
Main Results:
- At 3 months, ACR20 response rates were 50% (5 mg) and 47% (10 mg) for tofacitinib versus 24% for placebo (P<0.001).
- Mean HAQ-DI score changes were -0.39 (5 mg) and -0.35 (10 mg) for tofacitinib, versus -0.14 for placebo (P<0.001).
- Serious adverse events were more frequent in the tofacitinib groups; specific events included infections, myocardial infarction, and ischemic stroke.
Conclusions:
- Tofacitinib demonstrated superior efficacy over placebo in reducing disease activity in psoriatic arthritis patients with inadequate response to TNF inhibitors.
- Adverse events, including serious ones, were more common with tofacitinib treatment.
- The study highlights tofacitinib as a potential therapeutic option for refractory psoriatic arthritis, warranting careful monitoring for side effects.
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