Is 2nd JAKi treatment for UC worth the effort? A retrospective, multi-centre UK study.
Radia C., Danso Y., Ritchie S., Hale M., Elford AT., Patel C., Hicks L., Kalyanji S., Dong C., Yeung K., Yeo JH., Allah-Ditta M., Bishara M., Sethi-Arora K., Pillay L., Johnston EL., Rudling R., Rees F., Harvey P., Trodden-Mittnacht H., Davis E., Fraser A., Sawan NJ., Hussain MA., Campbell R., George B., Rawcliffe M., Choon XY., Shah K., Al-Zarrad D., Toft J., Chhabra P., Burr N., Hewitt A., Kumar R., McCartney S., Rosiou K., Dhar A., Lees CW., Lamb CA., Speight A., Ahmad T., Limdi J., Raine T., Walsh A., Cooney R., Harrow P., Patel K., Samaan M., Pavlidis P., Kent A., Selinger C., Kok KB.
Background and aimsJanus kinase inhibitors (JAKi) provide effective treatment for ulcerative colitis (UC), but inadequate response (IR) or intolerance occurs frequently. This study aimed to assess the effectiveness of a second JAKi in a real-world UC cohort.MethodsA retrospective multicenter cohort study encompassing 19 UK hospitals was undertaken. Primary outcome was clinical remission (Simple Clinical Colitis Activity Index/partial Mayo Score ≤ 1) at weeks 8 and 24, based on available assessments. Biochemical (CRP ≤ 5mg/L and fecal calprotectin ≤ 200µg/g) and endoscopic (Ulcerative Colitis Endoscopic Index of Severity/Mayo Endoscopic Subscore ≤ 1) remission were also assessed.ResultsA total of 131 patients with active UC were included. The majority (60%) had exposure to ≥3 advanced therapies and 50% required corticosteroids at induction. Clinical remission rates were 59% and 51% at weeks 8 and 24. Biochemical and endoscopic remission rates were 61% and 60% at week 8, and 47% and 32% at week 24. All disease activity parameters significantly reduced by week 8 (P < .001). At week 24 no difference was detected in clinical remission rates between those with primary non-response (42%) or secondary loss of response (52%) to their first JAKi (P = .518). Clinical remission did not differ between upadacitinib (54%) and filgotinib (36%), P = .253. Adverse events occurred in 27% of patients, and serious adverse events in 8%.ConclusionsIn this highly refractory cohort with active UC a second JAKi effectively achieved remission following IR to first JAKi. Type of first JAKi failure did not appear to influence clinical remission. No new safety signals were found.