Tofacitinib ( Xeljanz ), an orally administered Janus kinase inhibitor, blocks signaling through gamma-chain-containing cytokines ( interleukins 2, 4, 7, 9, 15, and 21 ).
Researchers have performed a phase 2 trial to measure efficacy of Tofacitinib in patients with moderate-to-severe active Crohn's disease.
Patients ( n=139; age, greater than or equal to 18 years ) with moderate-to-severe active Crohn's disease were assigned randomly to groups given 1 mg ( n= 36 ), 5 mg ( n=34 ), or 15 mg ( n=35 ) Tofacitinib or placebo ( n=34 ), twice daily for 4 weeks, at 48 centers in 12 countries.
The primary end point was the proportion of clinical responders at week 4 ( decrease from baseline in the Crohn's Disease Activity Index score of greater than or equal to 70 points [ Response-70 ] ). Secondary end points included clinical remission ( Crohn's Disease Activity Index score of greater than 150 points ) at week 4.
A clinical response was observed in 36% ( P = 0.467 ), 58% ( P = 0.466 ), and 46% ( P greater than or equal to 0.999 ) of patients given the 1-, 5-, and 15-mg doses of Tofacitinib, compared with 47% of patients given placebo.
Clinical remission was observed in 31% ( P = 0.417 ), 24% ( P = 0.776 ), and 14% ( P = 0.540 ) of patients given the 1-, 5-, and 15-mg doses of Tofacitinib, compared with 21% of patients given placebo.
The 15-mg dose of Tofacitinib reduced levels of C-reactive protein and fecal calprotectin from baseline.
Adverse and serious adverse events were similar among groups.
Dose-dependent increases in low- and high-density lipoprotein cholesterol were observed in patients given the 5- or 15-mg doses of Tofacitinib.
In conclusion, there were no significant differences in the percentage of patients with moderate-to-severe active Crohn's disease who achieved clinical responses ( Response-70 ) or clinical remission after 4 weeks' administration of Tofacitinib ( 1, 5, or 15 mg ) or placebo twice daily.
However, a large percentage of patients given placebo achieved Response-70 or remission.
Reductions in C-reactive protein and fecal calprotectin levels among patients given the 15-mg dose of Tofacitinib indicate its biologic activity. ( Xagena )
Sandborn WJ et al, Clin Gastroenterol Hepatol 2014; Epub ahead of print