Tofacitinib, either at 5 mg or 10 mg twice daily, maintains its safety profile for at least 9.5 years, with sustained efficacy for at least 8 years in rheumatoid arthritis, according to data from a long-term extension study published in Arthritis Research & Therapy.
“The efficacy and safety of tofacitinib 5mg and 10mg twice daily administered as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs, mainly methotrexate, in patients with moderately to severely active RA, have been demonstrated in phase 2 and phase 3 randomized controlled trials (RCTs) of up to 24months’ duration,” Jürgen Wollenhaupt, MD, of Rheumatologie Hamburg in Germany, and colleagues wrote.
“The efficacy and safety of therapy is typically evaluated via double-blind RCTs,” they added. “As RA is a chronic disease requiring long-term treatment, it is important to assess the long-term effectiveness and safety of RA therapies to understand the potential lifelong impact on patients’ health and quality of life.”
Tofacitinib, either at 5 mg or 10 mg twice daily, maintains its safety profile for at least 9.5 years, with sustained efficacy for at least 8 years in RA, according to data.
To analyze the safety and efficacy of tofacitinib (Xeljanz, Pfizer), in doses of either 5 mg or 10 mg twice daily, for up to 9.5 years, Wollenhaupt and colleagues conducted the ORAL Sequel study, an open-label, follow-up long-term extension of patients who had completed the trial’s prior phases. These included two phase 1 studies, eight phase 2 studies and six phase 3 studies. The extension itself included 4,481 participants with RA from 414 centers across 43 countries. Of these, 3,358 patients received twice-daily doses of 10 mg, while 1,123 participants were treated with doses of 5 mg twice daily.
Throughout the study, patients continued to receive stable background therapy, including conventional synthetic DMARDs, with adjustments to either tofacitinib or background therapy permitted at the researchers’ discretion. The participants’ assignments to either dose group was based on their average total daily dose in previous phases. In these qualifying index studies, tofacitinib had been dosed at 1 mg, 3 mg, 5 mg, 10 mg, 15 mg or 30 mg twice daily, or at 20 mg once daily, either as monotherapy or in combination with background therapy.
According to Wollenhaupt and colleagues, the total drug exposure amounted to 16,291 patient-years. The researchers were able to collect and analyze safety data for up to 114 months for all tofacitinib doses, with efficacy data reported for up to 96 months for the 5-mg group and 72 months for the 10-mg group. However, discontinuation rates and low patient numbers limited their ability to interpret the data beyond those time periods. In total, 52% of participants ultimately discontinued treatment, 24% of whom stopped due to adverse events, and 4% due to insufficient response.
The researchers found that tofacitinib’s safety profile remained consistent with what had been reported in previous phases, with an incident rate of 6.8 adverse events leading to discontinuation per 100 patient-years. Incident rates for specific events included 3.4 for herpes zoster, 2.4 for serious infections, 0.8 for malignancies excluding nonmelanoma skin cancer, 0.4 for major adverse cardiovascular events and 0.3 for all-cause mortality. Meaningful improvements in RA signs and symptoms, as well as physical function, were maintained from previous index studies through 8 years.
“Tofacitinib 5mg and 10mg [twice daily] demonstrated a consistent safety profile and sustained efficacy in this open-label [long-term extension] ORAL Sequel study of patients with RA,” Wollenhaupt and colleagues wrote. “Safety data are reported up to 9.5years, and efficacy data up to 8years, based on adequate patient numbers to support conclusions.”
“Furthermore, the safety profile of tofacitinib in patients who initiated tofacitinib as monotherapy was generally similar to that observed when tofacitinib was initiated in combination with [conventional synthetic] DMARDs,” the researchers added. “Tofacitinib 5mg and 10mg [twice daily] provided sustained improvement in signs and symptoms of RA and improvements in physical function.” – by Jason Laday
Disclosures : Wollenhaupt reports consulting and speaker fees, as well as honoraria from, Pfizer. Please see the full study for additional author disclosures.