Tofacitinib for the treatment of moderately to severely active ulcerative colitis: a systematic review, network meta-analysis and economic evaluation

Abstract

Background and aimsIn the UK, treatments for patients with moderately to severely active ulcerative colitis who have an inadequate response to conventional therapies comprise four biological therapies—the tumour necrosis factor inhibitor (TNFi) agents adalimumab, golimumab and infliximab and the anti-integrin vedolizumab—and an orally administered small molecule therapy, tofacitinib. However, there have been few head-to-head studies of these therapies. This study aimed to compare the clinical and cost-effectiveness of tofacitinib with biological therapies.MethodsA systematic literature review was conducted to identify all relevant randomised controlled trial (RCT) evidence. Clinical response, clinical remission and serious infection rates were synthesised using network meta-analysis (NMA). The results were used to compare the cost-effectiveness of tofacitinib and biologics with conventional therapy, using a Markov model, which incorporated lifetime costs and consequences of treatment from a UK National Health Service perspective. Analyses were conducted separately for TNFi-naïve and TNFi-exposed populations.ResultsSeventeen RCTs were used in the NMAs. There were no statistically significant differences among biological therapies and tofacitinib for either TNFi-naïve or TNFi-exposed patients. In TNFi-naïve patients, all therapies were more efficacious than placebo. In TNFi-exposed patients, only tofacitinib was significantly more efficacious than placebo as induction therapy, and only tofacitinib and vedolizumab were significantly more efficacious than placebo as maintenance therapies. There were no significant differences in serious infection rates among therapies. The incremental cost-effectiveness ratios for tofacitinib versus conventional therapy were £21 338 and £22 816 per quality-adjusted life year (QALY) in the TNFi-naïve and TNFi-exposed populations, respectively. TNFi therapies were dominated or extendedly dominated in both populations. Compared with vedolizumab, tofacitinib was associated with a similar number of QALYs, at a lower cost.ConclusionTofacitinib is an efficacious treatment for moderately to severely active ulcerative colitis and is likely to be a cost-effective use of NHS resources.

Cost-effectiveness analysis of using innovative therapies for the management of moderate-to-severe ulcerative colitis in Spain

“…Internationally, cost-effectiveness analyses including tofacitinib have indeed been published [41,42]. The results of these publications are consistent with the findings of this analysis.…”

Efficacy of JAK inhibitors in Crohn’s Disease

“…As mentioned above Tofacitinib (Pfizer Inc., New York, United States) has shown promising results for the treatment of UC and has been approved by FDA and EMA as well as other regulatory agencies (e.g. SwissMedic) 5,7,[53][54][55][56] . Tofacitinib is a rather broad JAK inhibitor that besides a main activity for JAK1 and JAK3 also inhibits tyrosine kinases outside the JAK family 2,55 .…”

“…SwissMedic]. 5 , 7 , 53–56 Tofacitinib is a rather broad JAK inhibitor that besides having a main activity for JAK1 and JAK3 also inhibits tyrosine kinases outside the JAK family. 2 , 55 Therefore, it has always been a matter of discussion whether its action can solely be attributed to JAK inhibition.…”

“…Subsequently, Janus kinase (JAK) inhibitors were considered for clinical trials in both CD and UC and clinical trials programs for different compounds from this substance class have been established for both IBD entities [2][3][4] . Tofacitinib, a pan-JAK inhibitor, in the meantime has been approved for the treatment of patients with moderate to severe UC [5][6][7][8][9][10][11] . Reports on the clinical testing of three JAK inhibitors in patients with moderate-to-severe CD have been published: tofacitinib (pan-JAK inhibitor) 10 , filgotinib (JAK1 inhibitor) 12 and upadacitinib (JAK1 inhibitor) 12 .…”

“… 2–4 Tofacitinib, a pan-JAK inhibitor, in the meantime has been approved for the treatment of patients with moderate to severe UC. 5–11 Reports on the clinical testing of three JAK inhibitors in patients with moderate to severe CD have been published: tofacitinib [pan-JAK inhibitor], 10 filgotinib [JAK1 inhibitor] 12 and upadacitinib [JAK1 inhibitor]. 12 …”