Systematic review with meta‐analysis: efficacy and safety of oral Janus kinase inhibitors for inflammatory bowel disease

Abstract

Background: Janus kinase (JAK) inhibitors represent a novel therapeutic class for treatment of inflammatory bowel disease. Aims:To determine the efficacy and safety of JAK inhibitors compared to placebo for the treatment of Crohn's disease (CD) and ulcerative colitis (UC). Methods:PubMed, Embase and CENTRAL were systematically searched to November 1, 2018. Randomised placebo-controlled trials (RCTs) of JAK inhibitors in adult patients with CD or UC were eligible. Open-label extension studies without a placebo comparator arm were excluded. Clinical, endoscopic, and safety outcomes were extracted and rates relative to placebo were pooled using a random-effects model. Results:A total of 12 RCTs (5 CD, 7 UC) were included. Patients were randomised to placebo (n = 844), tofacitinib (n = 1882), filgotinib (n = 130), peficitinib (n = 176), upadacitinib (n = 387) or TD-1473 (n = 31). JAK inhibitor treatment was associated with induction of clinical remission in CD (RR, relative risk 1.38 [95% confidence interval CI 1.04-1.83], P = 0.025, I 2 = 14%) and UC (RR 3.07 [95% CI 2.03-4.63], P < 0.001, I 2 = 0%). In UC, JAK inhibitor treatment was associated with induction of endoscopic remission (endoscopic Mayo subscore MCSe = 0/1) (RR 2.43 [95% CI 1.64-3.59], P < 0.001, I 2 = 27%) and mucosal healing (MCSe = 0) (RR 5.50 [95% CI 2.46-12.32], P < 0.001, I 2 = 0%). JAK inhibitor treatment increased the risk of infection compared to placebo (RR 1.40 [95% CI 1.18-1.67], P < 0.001, I 2 = 0%), particularly for herpes zoster. Conclusions: JAK inhibitors are effective for inducing clinical remission in CD and induction of clinical and endoscopic remission in UC, although are associated with an increased risk of infectious complications. R-Biopharm and Takeda and consulting fees from Janssen, Pfizer, Progenity, Prometheus, Takeda, and UCB. Reena Khanna has re-

Tofacitinib for ulcerative colitis: results of the prospective Dutch Initiative on Crohn and Colitis (ICC) registry

“…The rate of infections was comparable with vedolizumab (IBD: 38 per 100 patient years) and ustekinumab (CD: 36 per 100 patient years) . However, the limited follow‐up period could have biased these results as JAK inhibitors are associated with an increased risk of infections when compared with placebo (RR 1.40 [95% CI 1.18‐1.67], P < 0.0001) …”

“…A recent review of clinical trials showed a comparable safety profile of tofacitinib when compared with vedolizumab and anti‐TNF with the exception of herpes zoster infections/reactivations . Another systematic review of clinical trials showed no increased risk of adverse events when JAK inhibitors were compared with placebo . However, in these reviews, not the number of adverse events but the number of patients with adverse events was compared.…”

<p>Novel Therapeutic Options for People with Ulcerative Colitis: An Update on Recent Developments with Janus Kinase (JAK) Inhibitors</p>

“…Moreover, histologic improvement or remission were more frequent in upadacitinib-treated patients compared to placebo. 64,65 Filgotinib, a selective JAK1 inhibitor, is under investigation in a phase 2b/3 in patients with moderate-to-severe UC (NCT02914522). Currently, several other selective JAK1 inhibitors, such as SHR0302 and itacitinib (NCT03675477; NCT03627052), TYK2 inhibitor, such as BMS-986165 (NCT03934216) or gut-selective pan-JAK inhibitors such as TD-1473 (NCT03635112) are under investigation, and many others are being developed by the industries.…”

“…61 Excluding peficitinib, no complete publications of clinical data are currently available for the other compounds. 64…”

Letter: tofacitinib use for biologic‐refractory paediatric inflammatory bowel disease

“…We were interested to read the study by Ma et al 1 reporting that a janus kinase (JAK) inhibitor was effective induction therapy for a refractory population of adults with ulcerative colitis (UC) and Crohn's disease (CD). 2,3 Despite an increased risk of infection, with particular concern over herpes zoster, JAK inhibition was not associated with an increased risk of adverse events (AEs).…”