Safety and Efficacy of Long-term Tofacitinib Therapy in Patients with Active Psoriatic Arthritis – Interim Results of the OPAL Balance Study

Tofacitinib in OPAL Studies

Tofacitinib is an orally administered JAK inhibitor used in combination with methotrexate to treat active psoriatic arthritis in adult patients who do not respond adequately to or cannot tolerate disease-modifying antirheumatic drugs. The efficacy and safety of tofacitinib at doses of 5 and 10 mg twice daily in adults with psoriatic arthritis were evaluated in two randomized placebo-controlled phase III clinical studies, OPAL.

The OPAL Broaden study included 422 patients aged ≥ 18 years naive to previous treatment with tumor necrosis factor (TNF) inhibitors who had not achieved an adequate clinical response with ≥ 1 disease-modifying drug. The total duration of the study was 12 months. In the 6-month OPAL Beyond study, 394 patients who had not achieved an adequate clinical response with ≥ 1 TNF inhibitor were enrolled. Both studies demonstrated the superiority of tofacitinib over placebo after 3 months of therapy, with higher rates of adverse events with tofacitinib compared to placebo.

Following these two clinical studies, the long-term extension study OPAL Balance was designed, enrolling eligible patients from the OPAL Beyond and OPAL Broaden studies within ≤ 3 months of their completion. Patients entered the OPAL Balance study if they had completed the previous studies or had discontinued for reasons other than treatment-related adverse events. The goal of the extended study was to evaluate the long-term efficacy (up to 30 months) and safety (up to 36 months) of the therapy.

Study Methodology

The OPAL Balance study was designed as an open-label phase III clinical extension study, conducted at 124 clinical centers in 16 countries. Patients were administered tofacitinib at a dose of 5 mg twice daily, with the dose increased to 10 mg twice daily if there was insufficient clinical response after the first month of therapy or at any subsequent clinical follow-up. The dose of tofacitinib could later be reduced to the initial dose if adverse events were suspected. Patients could concurrently receive stable doses of oral corticosteroids, nonsteroidal anti-inflammatory drugs, or cyclooxygenase 2 (COX-2) inhibitors.

The primary objective of the study was to evaluate the long-term safety and tolerability of the therapy (in the form of adverse events and laboratory abnormalities), and the secondary objective was to evaluate the long-term efficacy of the therapy.

Interim Analysis Results

Definitive results of the study are not currently available; the presented data represent interim analysis results up to August 31, 2017.

A total of 686 patients (363 from the OPAL Broaden study and 323 from OPAL Beyond) participated in the OPAL Balance study. During the data collection period, 68.2% of the original number of patients (n = 468) remained in the study. The average duration of therapy was 614 days (range 1–1032 days). The total duration of therapy was 1153.2 patient years. After 36 months of therapy, adverse events were reported in 79.6% of patients, serious adverse events in 13.8%, and treatment discontinuation due to adverse events in 8.6%. Adverse events occurring in ≥ 5% of patients included upper respiratory tract infections, nasopharyngitis, urinary tract infection, bronchitis, and hypertension. A total of 5 patients died during the study (1 death during the 28-day risk period), with an incidence rate of 0.1/100 patient-years.

The incidence rate of adverse events of special interest was 1.7/100 patient-years for all cases of herpes zoster, 0.9 for serious infections, 0.3 for opportunistic infections, 0.8 for malignancies excluding non-melanoma skin cancer, 1.0 for non-melanoma skin cancers, 0.3 for major cardiovascular events, 0.1 for pulmonary embolism, and 0.4 for arterial thromboembolic disease.

There were no reports of deep vein thrombosis during the study. In terms of laboratory parameters, an increase ≥ 3 times above the upper limit was noted in ALT (4% of patients) and AST (2.2%). Changes in laboratory parameters were generally stable during the study, with a slight decrease in lymphocyte count observed.

Across all therapeutic groups, stable efficacy of the therapy was achieved over 30 months, evaluated by various clinical parameters (ACR20, ACR50, ACR70, PsARC, PASI75, MDA, and others).

Conclusion

Interim analysis of the OPAL Balance clinical study suggests that the efficacy and safety of tofacitinib in patients with active psoriatic arthritis are comparable in the long-term with the results of previous clinical studies evaluating tofacitinib over 6 and 12 months. Stable efficacy of therapy was observed even after 30 months of tofacitinib therapy across all therapeutic groups.

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Source: Nash P., Coates L. C., Kivitz A. J. et al. Safety and efficacy of tofacitinib in patients with active psoriatic arthritis: interim analysis of OPAL Balance, an open-label, long-term extension study. Rheumatol Ther 2020; 7 (3): 553–580, doi: 10.1007/s40744-020-00209-4.