Study data published in Digestive Diseases and Sciences outline the impact of tofacitinib treatment on creatine kinase in patients with ulcerative colitis (UC). While tofacitinib was associated with elevated creatine kinase levels after 8 weeks of treatment, the effect appeared reversible and was not associated with significant adverse events. These results are consistent with other studies assessing creatine kinase levels in non-UC inflammatory diseases.
Investigators extracted data from existing studies of tofacitinib for the treatment of inflammatory disorders. Patients from these studies were classified into 3 cohorts for the purposes of analyses: (1) the Induction cohort, comprising patients who had received either placebo or tofacitinib 10 mg twice daily in phase 2 or phase 3 induction studies; (2) the Maintenance cohort, comprising patients who received either placebo, tofacitinib 5 mg twice daily, or tofacitinib 10 mg twice daily in a maintenance study; and (3) the Overall cohort, comprising all patients who received at least 1 dose of tofacitinib 5 mg or 10 mg in any of the aforementioned studies. In all cohorts, creatine kinase levels were monitored at regular intervals. Mean changes in creatine kinase levels from baseline were calculated. Adverse events were also reported by all cohorts; incidence rates were calculated for each event of interest.
The analysis cohort comprised 1157 patients with UC who received treatment with tofacitinib, including 938 in the Induction cohort and 394 in the Maintenance cohort (tofacitinib 5 mg n=198; tofacitinib 10 mg n=196). Mean age in the overall cohort was 41.3±13.9 years, and 41.3% of patients were women.
Median (range) creatine kinase level at baseline was 63.0 (7.0-3173.0) units per liter (U/L). Mean change from baseline to week 8 was +91.1 U/L (95% CI, 48.1-134.1) with tofacitinib 10 mg twice daily compared with just +19.2 U/L (8.5-29.9) with placebo. Among patients who completed 8 weeks of induction and were re-randomized to 52 weeks of maintenance therapy, mean changes from pre-induction baseline to week 52 were +35.9 U/L (95% CI, 8.1–63.7), +90.3 U/L (95% CI, 51.9–128.7), and +115.6 U/L (95% CI, 91.6–139.7), with placebo, tofacitinib 5 mg, and tofacitinib 10 mg, respectively.
The incidence rate for elevated creatine kinase-associated adverse events was 6.6 per 100 patient-years in the overall cohort. No serious adverse events associated with elevated creatine kinase were observed. The adverse event profile in patients with UC was similar to that of patients who received tofacitinib for rheumatoid arthritis, psoriasis, and psoriatic arthritis.
Pooled data from clinical trials of tofacitinib suggest that while the drug may result in elevated creatine kinase levels, the effect may not precipitate serious side effects. However, between-cohort heterogeneity may have affected outcomes. Analyses of subgroups defined by disease duration, treatment history, and concomitant medications may reveal different responses to tofacitinib.
One study limitation is the pooling of potentially heterogenous patient populations for analysis in the Overall cohort, as well as differences in patient prior treatment history and permitted concomitant medications. Finally, the study was limited by site reporting and interpretation of potential adverse events associated with creatine kinase elevation.
“In patients with UC, [creatine kinase] elevations with tofacitinib appeared reversible and not associated with clinically significant [adverse events]. UC findings were consistent with tofacitinib use in other inflammatory diseases,” the investigators concluded.
Disclosure: Several study authors declared affiliations with the pharmaceutical industry.
Please see the original reference for a full list of authors’ disclosures.
Panaccione R, Isaacs JD, Chen LA, et al. Characterization of creatine kinase levels in tofacitinib-treated patients with ulcerative colitis: results from clinical trials. Published online August 20, 2020. Dig Dis Sci. doi: 10.1007/s10620-020-06560-4