Abstract
Tofacitinib, a selective inhibitor of JAK/STAT pathway, has recently become available in our region. Here, we examined the safety and efficacy of tofacitinib in active ulcerative colitis (UC). In a prospective, non-randomized, placebo-free, 52-week clinical trial defined in two phases of induction and maintenance, adult patients with active UC and no response or loss of response to previous conventional treatments, or anti-TNF were recruited (IRCT20181217042020N2). Patients received 10 mg/BID of tofacitinib for 8 weeks. Clinically responding patients were entered into the maintenance phase and received tofacitinib 5 mg/BID for 44 weeks. Clinical evaluation, biochemical tests and endoscopy at time points of baseline, 8, 24 and 52 weeks were performed. The primary outcome was clinical remission at 8 and 52 weeks. Fifty out of 53 enrolled patients completed the induction phase. Clinical response and clinical remission at 8 weeks occurred in 84% and 9.5%, respectively. Forty-two patients who had clinical response entered the maintenance phase. Clinical remission based on the total Mayo score and the partial Mayo score occurred in 38.9% and 55.3% at 24 weeks and in 61.1% and 72.2% at 52 weeks, respectively. There was significant correlation between the total and partial Mayo score with regard to clinical remission in both 24 and 52 weeks. No serious adverse events, no case of herpes zoster, but two cases of deep vein thrombosis were seen. Our study showed acceptable efficacy and safety for tofacitinib and suggested a correlation between the total Mayo score with partial Mayo score with regard to clinical remission.
Highlights
Inflammatory bowel disease (IBD), a chronic autoimmune disorder of the gastrointestinal tract, is typically classified into two main subtypes of ulcerative colitis (UC) and Crohn’s disease (CD)
Newer therapy approaches are relying on interfering with cytokine signaling events, including those dependent on the Janus kinase (JAK) family of tyrosine kinases and the signal transducer and activator of transcription (STAT) family of DNA-binding proteins.[6]
Safety was assessed based on serious adverse events (SAEs), adverse events (AEs) defined as any AE regardless of relationship to study drug, and laboratory abnormalities according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Summary
Inflammatory bowel disease (IBD), a chronic autoimmune disorder of the gastrointestinal tract, is typically classified into two main subtypes of ulcerative colitis (UC) and Crohn’s disease (CD). Patients with UC, the more common subtype of IBD, might present with intermittent episodes of disease activation with symptoms of rectal bleeding, diarrhea, abdominal cramps, urgency or tenesmus, and fever.[4] The mucosal inflammation with a relapsing and remitting nature usually starts in the rectum and extends to proximal segments of the colon.[4] While the initial mechanisms underlying the highly complex pathogenesis of the disease are still under debate, the crucial role of inflammatory cytokines in controlling intestinal inflammation and the associated clinical symptom, once the disease is established, has been well documented and monoclonal antibodies targeting key cytokines (for example, TNF) are frequently used for treatment of patients with refractory UC.[5,6] Newer therapy approaches are relying on interfering with cytokine signaling events, including those dependent on the Janus kinase (JAK) family of tyrosine kinases and the signal transducer and activator of transcription (STAT) family of DNA-binding proteins.[6] In vivo and clinical studies showed lines of evidence indicating that JAK-STAT signaling is required to mediate the cytokine function and that JAK inhibitors can block. We conducted a clinical trial and we report the efficacy and safety of tofacitinib (Iranian generic) as induction and maintenance therapy for moderately to severely active UC
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