Xeljanz appears safe for UC treatment despite herpes zoster risk - Healio

Xeljanz — a small-molecule Janus kinase inhibitor — appeared safe for the treatment of patients with moderate-to-severe ulcerative colitis, based on more than four years of data from global clinical trials published in Clinical Gastroenterology and Hepatology.

William J. Sandborn, MD, of the division of gastroenterology at the University of California San Diego, and colleagues wrote that the drug’s (tofacitinib, Pfizer) safety profile in UC generally mirrored that of anti-TNF therapies and with tofacitinib for rheumatoid arthritis except for higher rates of herpes zoster.

“Increased rates of [herpes zoster] have previously been observed with tofacitinib in other disease populations. In the UC maintenance cohort, a dose relationship in the risk of [herpes zoster] was demonstrated,” they wrote. “Most [herpes zoster] events were limited to cutaneous involvement over one or two adjacent dermatomes and did not require permanent discontinuation.”

To explore the drug’s safety profile, researchers analyzed data from patients who received placebo or tofacitinib (5 mg or 10mg) twice daily. They assessed the data based on three cohorts; induction (phase 2 or 3 induction studies; n = 1,220), maintenance (phase 3 maintenance study; n = 592) and overall (phase 2, phase 3, open-label, or long-term extension studies; n = 1,157) and determined incidence rates for adverse events as patients with events per 100 patient-years of exposure.

Investigators found that a numerically higher incidence rate for herpes zoster among patients who received 5 mg tofacitinib twice daily (incidence rate [IR] = 2.1; 95% CI, 0.4–6) and a statistically higher incidence rate for patients who received 10 mg tofacitinib twice daily (IR = 6.6; 95% CI, 3.2–12.2) compared with placebo (IR = 1; 95 % CI, 0–5.4).

In the overall cohort, researchers found similar rates of adverse events as have been experienced in anti-TNF agents, as well as tofacitinib for the treatment of rheumatoid arthritis.

“The safety profile of tofacitinib in the UC clinical development program was manageable,” Sandborn and colleagues wrote. “Tofacitinib treatment in patients with UC was associated with dose dependent risk of [herpes zoster]. Compared to prior experience with tofacitinib in rheumatoid arthritis, no new or unexpected safety signals were identified. These safety findings support the long-term use of tofacitinib 5 and 10 mg [twice daily] in patients with moderately to severely active UC.” – by Alex Young

Disclosures: The studies were sponsored by Pfizer. Sandborn reports receiving grant support, personal fees or non-financial support from the ACG, Actavis, Actogenix NV, Adherion Pharmaceuticals, Akros Pharma, Am Pharma BV, Ambrx Inc., Amgen, Ardelyx, Arena Pharmaceuticals, Atlantic Pharmaceuticals, Avaxia Biologics, Baxter Healthcare, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, the Broad Foundation, Catabasis Pharmaceuticals, Celgene, Celgene Cellular Therapeutics, Chiasma, Cosmo Pharmaceuticals, Dr. August Wolff, Eisai, Eli Lilly, Exact Sciences, Ferring Pharmaceuticals, Ferring Research Institute, Forward Pharma, Galapagos, Genentech, Gilead Sciences, Hakko Lexicon Pharmaceuticals, Immune Pharmaceuticals, Index Pharmaceuticals, Ironwood Pharmaceuticals, Janssen, Kirin, Kyowa Lipid Therapeutics GmbH, Luitpold Pharmaceuticals, MedImmune (AstraZeneca), Mesoblast Inc., Millennium Pharmaceuticals, Nestle, Novo Nordisk, Nutrition Science Partners, Orexigen, Palatin, Pfizer, Prometheus Laboratories, Qu Biologics, Regeneron, Ritter Pharmaceuticals, Salix Pharmaceuticals, Santarus, Seattle Genetics, Seres Health, Shire, Sigmoid Biotechnologies, Takeda, Teva Pharmaceuticals, Theradiag, Theravance, TiGenix, Tillotts Pharma, Toray Industries Inc., UCB Pharma, The University of Western Ontario (owner of Robarts Clinical Trials), Vascular Biogenics, Vertex Pharmaceuticals, Warner Chilcott, and Zyngenia. Please see the full study for all other authors relevant financial disclosures.

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