LAS VEGAS — Xeljanz induced remission in subgroups of patients with moderate-to-severe Crohn’s disease who showed objective evidence of disease activity at baseline, according to a post hoc analysis of a phase 2 trial presented at the Crohn’s & Colitis Congress.
Xeljanz (tofacitinib, Pfizer) has previously shown greater response rates among patients with ulcerative colitis vs. Crohn’s disease, so these results support further investigation for the use of JAK inhibitors in Crohn’s disease, investigators concluded.
“Tofacitinib is an oral small molecule [Janus kinase (JAK)] inhibitor that has been investigated for inflammatory bowel disease,” Bruce E. Sands, MD, professor of medicine and gastroenterology at the Icahn School of Medicine at Mount Sinai, said during his presentation. While the drug has been shown to be effective in phase 3 studies in ulcerative colitis, “very small treatment effects were observed in Crohn’s disease patients.”
Previously reported results from this phase 2b multicenter randomized controlled trial — in which patients received 5 mg or 10 mg of tofacitinib or placebo twice daily for 8 weeks — indeed showed small treatment effects in patients with moderate-to-severe Crohn’s disease, but enrollment criteria were based on Crohn’s Disease Activity Index (CDAI) scores without endoscopic scoring.
“Simply, the patients had to have evidence of ulceration to be enrolled in this study,” Sands said. “We hypothesized that part of the problems with these studies were the lack of objective criteria of inflammation at baseline, and therefore we performed a post hoc analysis of efficacy endpoints,” based on more objective baseline criteria of disease activity.
Sands and colleagues re-analyzed data on patient subgroups using endoscopic and biomarker evidence of inflammation, including C-reactive protein (CRP) and fecal calprotectin levels. They also explored composite remission (CDAI less than 150 and either a decrease from baseline CRP or fecal calprotectin by 50% or more) and composite response (decrease from baseline CDAI of 100 or more and either a decrease from baseline CRP or fecal calprotectin by 50% or more).
They found that significantly more tofacitinib vs. placebo patients who had Simple Endoscopic Scores (SES-CD) greater than 11 at baseline achieved clinical remission (48.9% with 10 mg vs. 23.4% with placebo), composite remission (25.5% with 10 mg and 26% with 5 mg vs. 6.4% with placebo) and composite response (36.2% with 10 mg and 46% with 5 mg vs. 17% with placebo; P < .05 for all). They also saw similar results among patients with CRP levels greater than 5 mg/L or fecal calprotectin levels greater than 250 mg/kg at baseline.
Sands noted that they also found that patients with SES-CD scores lower than 11 at baseline showed significantly higher rates of composite remission and composite response with tofacitinib vs. placebo (P < .05 for all except composite remission in the 5-mg group).
“Greater proportions of tofacitinib patients were in clinical remission as compared to placebo when efficacy outcomes were analyzed using some more objective baseline criteria for active disease than CDAI,” Sands concluded. “Greater proportions of patients achieved composite remission, composite response, and PRO2-75 remission ... compared with placebo, but there has to be caution of course that these are all post hoc analyses. Nevertheless, I think they support further investigation of JAK inhibition in Crohn’s disease.” – by Adam Leitenberger
Sands BE, et al. Abstract 14. Presented at: Crohn’s & Colitis Congress; Jan. 19-20, 2018; Las Vegas, NV.
Disclosures: Sands reports financial relationships with Pfizer, AbbVie; Allergan, Boehringer-Ingelheim, Celgene, Gilead, Janssen, Lilly, MedImmune, Shire, Takeda, Target PharmaSolutions, UCB, Theravance Biopharma, TiGenix, TopiVert Pharma, Vivelix Pharmaceuticals, EnGene, Lyndra and Oppilan Pharma. Please see the full abstract for all other authors’ relevant financial disclosures.