Safety Profile of Tofacitinib Similar to Other Systemic Therapies in Psoriatic Arthritis

Psoriatic Arthritis on Hand
Psoriatic Arthritis on Hand
Researchers compared the incidence rates of adverse events in tofacitinib clinical trials and real-world observational data for other treatments.

For patients with psoriatic arthritis (PsA), tofacitinib demonstrates a safety profile similar to other systemic therapies used in real-world studies, according to research results published in Drug Safety.

Using data from 2 phase 3 clinical trials ( Identifiers: NCT01877668, NCT01882439, and NCT01976364, respectively), and 1 ongoing, long-term extension study, researchers compared incidence rates for adverse events of special interest from the tofacitinib PsA clinical program with those from PsA treatments collected through the US Truven MarketScan database.

Investigators defined 3 cohorts for analysis: the tofacitinib placebo-controlled cohort, which included data from the placebo-controlled part of the phase 3 studies from months 0 to 3; the tofacitinib dose-comparison cohort, which included the same treated patients at baseline but included data from the length of the entire study; and the all-tofacitinib comparison cohort, which included data from all patients who received ≥1 dose of tofacitinib in any of the studies. Investigators analyzed adverse events, serious adverse events, deaths, and adverse events leading to discontinuation.

The final placebo-controlled cohort included 474 tofacitinib-treated patients, 106 adalimumab-treated patients, and 236 placebo-treated patients. The final tofacitinib dose-comparison cohort included the same tofacitinib-treated patients as the placebo-controlled cohort. At baseline, the lowest percentage of patients who received corticosteroids (15.7%) was in the group receiving tofacitinib 10 mg twice per day, and the highest percentage (28.2%) was in the group receiving tofacitinib 5 mg twice per day. All patients received 1 background, conventional synthetic disease-modifying antirheumatic drug (DMARD), with most patients receiving methotrexate (75.5%-81.8%).

The all-tofacitinib comparison cohort included 783 tofacitinib-treated patients, with a total of 776 patient-years of tofacitinib across all dose exposures. Investigators identified data from 5799 patients through the US Truven MarketScan database, and their demographic data were comparable with data from patients in the all-tofacitinib comparison cohort.

Headache, nasopharyngitis, and upper respiratory tract infection were the most commonly reported adverse events in the placebo-controlled cohort. In the dose-comparison cohort, incidence rates (IRs) for serious adverse events over 12 months in the tofacitinib 5 mg and 10 mg groups were 7.9 (95% CI, 4.1-13.8) and 8.1 (95% CI, 4.2-14.2), respectively. Eleven patients discontinued receiving tofacitinib treatment because of adverse events (IR, 7.2 [95% CI, 3.6-12.8] and IR, 7.3 [95% CI, 3.7-13.1], for 5 mg and 10 mg, respectively).

In the tofacitinib dose-comparison cohort, 2 patients who received tofacitinib 5 mg and 3 patients who received tofacitinib 10 mg experienced serious infections (IR, 1.3 [95% CI, 0.2-4.7] and IR, 2.0 [95% CI, 0.4.-5.8], respectively). All serious infections were because of hospitalizations. Patients in the observational comparison cohort had an IR of 2.2 (95% CI, 1.4-3.2) for serious infections with biologic DMARDs, which ranged from 1.1 to 7.9 across all treatments.

Herpes zoster events were reported for 7 patients in the tofacitinib dose-comparison cohort (3 who received tofacitinib 5 mg and 4 who received tofacitinib 10 mg). Sixteen patients in the all-tofacitinib cohort also reported herpes zoster events (IR, 2.1 [95% CI, 1.2-3.3]). Three adjudicated opportunistic infections were noted in the all-tofacitinib comparison cohort (2 who received tofacitinib 5 mg and 1 who received tofacitinib 10 mg; IR, 0.4 [95% CI, 0.1-1.1]). In the observational comparison cohort, these IRs ranged from 0.9 to 3.8 across treatments.

Three patients in the all-tofacitinib comparison cohort reported major adverse cardiovascular events (IR, 0.4 [95% CI, 0.1-1.1]), with IRs for these events in the observational comparison cohort ranging from 0.0 to 0.7 across treatments.

Five patients in the all-tofacitinib comparison cohort reported malignancies (IR, 0.6 [95% CI, 0.2-1.5]), including bladder transitional cell carcinoma, renal cell carcinoma, and metastatic pancreatic cell carcinoma. Nonmelanoma skin cancer was reported in 4 patients in the all-tofacitinib comparison cohort (IR, 0.5 [95% CI 0.1-1.3]). In the observational comparison cohort, IRs for malignancies ranged from 0.0 to 1.1 across treatments, and IRs for nonmelanoma skin cancer ranged from 0.4 to 6.0.

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A total of 4 deaths were noted in the tofacitinib PsA clinical program; 2 in the all-tofacitinib comparison cohort among patients taking tofacitinib 5 mg, and 2 outside of the 28-day risk period. All deaths were unrelated to the study drug.

Study limitations included the use of limited time periods for comparison with placebo, limits in evaluations because of sample size, and differences in adverse event reporting across clinical trials.

“Tofacitinib had a safety profile that was generally consistent with patients with PsA receiving other therapies in real-world settings,” the researchers concluded. “Longer-term follow-up and larger patient populations will provide further information on the safety profile of tofacitinib in patients with PsA.”

Disclosure: This study was supported by Pfizer Inc. Please see the original reference for a full list of authors’ disclosures.


Burmester GR, Curtis JR, Yun H, et al. An integrated analysis of the safety of tofacitinib in psoriatic arthritis across Phase III and long-term extension studies with comparison to real-world observational data [published online January 31, 2020]. Drug Saf. doi:10.1007/s40264-020-00904