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Tofacitinib shows promise for Crohn's disease in select patients

Pearl Toh
08 Feb 2018

Using the JAK* inhibitor tofacitinib as induction therapy for Crohn’s disease (CD) can promote disease remission in certain patients selected based on baseline endoscopic evidence of inflammation, according to a post hoc analysis presented at the recent Crohn's & Colitis Congress (CCC) 2018, Las Vegas, Nevada, US.  

The multicentre, double-blind, phase IIb study randomized patients with moderate to severe CD (CD Activity Index [CDAI] 220–450) to placebo, tofacitinib 5 or 10 mg twice daily for 8 weeks. They were stratified by subgroups based on baseline simple endoscopic score (SES) <11, SES ≥11, or biomarkers for inflammation (CRP** ≥5 mg/L or FCP*** ≥250 mg/kg). At week 8, they were assessed for clinical remission (CDAI <150), composite remission (defined as remission and ≥50 percent CRP or FCP reduction from baseline), clinical response-100 (ie, ≥100 CDAI reduction from baseline), and composite response (including CDAI-100 response and ≥50 percent CRP or FCP reduction from baseline). [CCC 2018, abstract 14]  

In the subgroup with baseline SES ≥11 (n=144), significantly more tofacitinib-treated patients achieved clinical remission, composite remission, and composite response compared with the placebo group (p<0.05 for all, except clinical remission for the tofacitinib 5 mg arm).

Similarly in patients with baseline SES <11 (n=117), rates of composite response and composite remission were significantly higher with both doses of tofacitinib vs placebo (p<0.05 for all, except composite remission with tofacitinib 5 mg).

Significantly higher rates of composite response (p<0.01) and composite remission (p<0.05) were also observed with both doses of tofacitinib vs placebo in patients with baseline CRP ≥5 mg/L or FCP ≥250 mg/kg (n=183).

Tofacitinib, previously approved for rheumatoid arthritis treatment, is currently being investigated for ulcerative colitis and CD. Previous reports have demonstrated that response rates to the drug were greater in ulcerative colitis than in CD, with a recent trial showing minor treatment effects for tofacitinib in CD compared with placebo among patients enrolled based on simple CDAI criteria without endoscopic scoring. [Gut 2017;66:1049-1059]

“Increased proportions of patients were in remission and achieved composite remission and composite response with tofacitinib vs placebo, when analyses were done using more objective baseline criteria of active disease,” said lead author Dr Bruce Sands from Icahn School of Medicine at Mount Sinai New York, New York, US. “Results from these post hoc analyses support further investigation of JAK inhibition in CD.”

A separate molecular analysis [CCC 2018, abstract P135] on the mechanism behind the treatment effects of tofacitinib on CD showed that the cytokines TNFa, MCP-1, GM-CSF, IL-6, and IL-8 were inhibited more frequently with tofacitinib than with control vehicle, based on multiplex cytokine analysis and RNAseq analysis of punch biopsies from inflamed mucosa of patients with CD (n=12).

“Our study provides biological evidence that tofacitinib treatment might be beneficial in patients with CD,” said the researchers. “[Our assay] can be used to select patients with inflammatory bowel disease [IBD] more likely to respond to tofacitinib and guide tailored therapies in IBD.”

 

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Most Read Articles
3 days ago
A strong belief in the necessity of medication is associated with better adherence to oral disease-modifying antirheumatic drugs (DMARDs) or prednisone, while higher self-efficacy correlates with poor adherence, in a diverse cohort of patients with rheumatoid arthritis (RA), suggests a study.
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