Xeljanz appears safe for long-term UC treatment despite herpes zoster risk
WASHINGTON — Xeljanz, an oral small molecule Janus kinase inhibitor recently approved for ulcerative colitis, showed “an overall manageable safety profile” at up to 4.4 years in patients with UC, although there was a dose-dependent risk for herpes zoster, according to data from the OCTAVE studies presented at Digestive Disease Week.
“Based on the maintenance and overall cohorts, the risk of serious infection, opportunistic infection, herpes zoster, malignancy, non-melanoma skin cancer or [major adverse cardiovascular events] didn’t seem to increase with longer duration of tofacitinib [Xeljanz, Pfizer] up to 4.4 years,” William J. Sandborn, MD, of University of California, San Diego, said during his presentation. “These data are consistent with previous integrated safety analyses of the cohorts for up to 3.9 years. ... The overall safety profile of tofacitinib at 5 and 10 mg [twice daily] seemed to be manageable and was generally similar to that of tofacitinib in rheumatoid arthritis, and with the exception of herpes zoster, the safety of tofacitinib ... seemed to be similar to other UC therapies including biologics.”
Sandborn and colleagues performed an integrated safety analysis of data from the drug’s global clinical development program in UC, with exposure of up to 4.4 years. They analyzed data through December 2016 from the phase 2/3 induction trial (n = 1,220), the phase 3 maintenance trial (n = 592) and the overall cohort including data from phase 2, phase 3, and the ongoing open-label long-term extension study (n = 1,157; 1,613 patient-years of exposure).
The investigators reported that adverse events of interest were comparable between treatment and placebo groups in the induction studies, but in the maintenance phase the incidence rate of herpes zoster was numerically higher among patients who received 5 mg tofacitinib twice daily (IR = 2.1) and significantly higher among patients who received the 10 mg twice daily dose (IR = 6.6) compared with placebo (IR = 1).
“The majority of discontinuations due to adverse events in the maintenance cohort were due to worsening UC,” Sandborn noted.
Most patients received an average dose of 10 mg tofacitinib twice daily in the overall cohort (n = 971; 84%). The IRs for adverse events of interest in the overall cohort were as follows:
- death (IR = 0.2);
- serious infection (IR = 2);
- opportunistic infections (IR = 1.3);
- herpes zoster (IR = 4.1);
- malignancy (excluding non-melanoma skin cancer; IR = 0.5);
- non-melanoma skin cancer (IR = 0.7);
- major adverse cardiovascular events (IR = 0.2); and
- gastrointestinal perforations (IR = 0.2).
Sandborn concluded that malignancy rates are relatively low and numerically higher in the placebo groups, and that the side effect of herpes zoster may be addressed in clinical practice by vaccinating patients. – by Adam Leitenberger
Sandborn WJ, et al. Abstract 904. Presented at: Digestive Disease Week; June 2-5, 2018; Washington, D.C.
Disclosures: Sandborn reports financial ties to Qu Biologics, Seattle Genetics, Avaxia, Celgene, Takeda, Medimmune, Arena Pharmaceuticals, Ferring Research Institute, Ambrx, Kyowa Hakko Kirin Pharma, AbbVie, Palatin, Akros Pharma, UCB Pharma, Index Pharmaceuticals, Vascular Biogenics, and Atlantic Healthcare Pharmaceuticals. Please see the DDW faculty disclosure index for a list of all other authors’ relevant financial disclosures.