According to a systematic review and meta-analysis, Janus kinase (JAK) inhibitors are a safe and effective treatment for patients with acute severe ulcerative colitis (ASUC) as adjunct therapy to corticosteroids and rescue therapy.
Standard therapy for patients with ASUC is corticosteroids, with a response rate of 60%.
JAK inhibitors such as tofacitinib, upadacitinib, and filgotinib, have been approved for patients with ulcerative colitis with an intolerance or inadequate response to biologics, but their use for the treatment of ASUC remains off-label.
For tofacitinib, there was no difference in efficacy when comparing high-dose (pooled short-term clinical response, 80.7%) to standard-dose (pooled short-term clinical response, 77.1%).
Dr. Jena and colleagues concluded that JAK inhibitors “are promising and effective options in the management of patients with ASUC with good rates of clinical response and remission and low colectomy rates at short- (<1 month), intermediate- (<3 months), and long-term (3-12 months) follow-up.”
According to a systematic review and meta-analysis, Janus kinase (JAK) inhibitors are a safe and effective treatment for patients with acute severe ulcerative colitis (ASUC) as adjunct therapy to corticosteroids and rescue therapy.
Standard therapy for patients with ASUC is corticosteroids, with a response rate of 60%. Common salvage therapy options include infliximab, cyclosporine, and surgery. Despite rescue therapies, 20% of patients will require colectomy – and there are several limiting factors to both infliximab and cyclosporine that create the need for alternate approaches. JAK inhibitors such as tofacitinib, upadacitinib, and filgotinib, have been approved for patients with ulcerative colitis with an intolerance or inadequate response to biologics, but their use for the treatment of ASUC remains off-label. As Dr. Anuraag Jena, MD, Institute of Medical Sciences and SUM Hospital, Bhubaneswar, India, and colleagues noted, “Because patients with ASUC are excluded from licensing trials, the evidence on the efficacy and safety of JAK inhibitors will be pertinent in management algorithms.” Dr. Jena and colleagues conducted a systematic review and meta-analysis
They included 35 studies on JAK inhibitors in acute severe ulcerative colitis from PubMed, Embase, and Scopus, representing 664 patients. There were 19 studies reporting on tofacitinib, 15 on upadacitinib, 1 on both tofacitinib and upadacitinib, and none reporting on the use of filgotinib. Outcomes included pooled clinical response rates, remission rates, and colectomy at less than 30 days of therapy, less than 3 months of therapy, and 3 to 12 months of therapy.
In the short-term period of less than 1 month of therapy, the pooled clinical response rate and colectomy rate for tofacitinib were 77.9% and 11.5%, compared to 86.5% and 11.2% for upadacitinib. In the intermediate-term period of more than 3 months of therapy, the pooled clinical response rate, remission rate, and colectomy rate were 57.2%, 37.3%, and 16.1% for tofacitinib, compared to 56.1%, 47.4%, and 21.2% for upadacitinib. In the long-term period of 3 to 12 months of therapy, the pooled clinical response rate, remission rate, and colectomy rate were 41.4%, 33.8%, and 22.6% with tofacitinib, compared to 35.1%, 37.5%, and 23.4% with upadacitinib. Dr. Jena and colleagues noted that while upadacitinib “may be more potent than tofacitinib for the induction of clinical remission in moderate to severe UC,” outcomes were similar between the two agents in the setting of ASUC.
The most common adverse events reported were acne in 12.9% of patients, infection in 8.8% with herpes zoster in 3.4%, lipid abnormalities in 6.3%, venous thromboembolism in 2.2% of patients, and major adverse cardiovascular events in 0.7% of patients. For tofacitinib, there was no difference in efficacy when comparing high-dose (pooled short-term clinical response, 80.7%) to standard-dose (pooled short-term clinical response, 77.1%).
Dr. Jena and colleagues concluded that JAK inhibitors “are promising and effective options in the management of patients with ASUC with good rates of clinical response and remission and low colectomy rates at short- (<1 month), intermediate- (<3 months), and long-term (3-12 months) follow-up.”
