DOP44 Tofacitinib versus corticosteroids for induction of remission in moderately active ulcerative colitis (ORCHID): A prospective randomized open-label pilot study
SinghD.M., A.(1)*;Midha, V.(2);Mahajan, R.(1);Kaur, K.(3);Singh, D.(4);Sood, A.(1);
(1)Dayanand Medical College and Hospital, Gastroenterology, Ludhiana, India;(2)Dayanand Medical College and Hospital, Medicine, Ludhiana, India;(3)Dayanand Medical College and Hospital, Pharmacology, Ludhiana, India;(4)Dayanand Medical College and Hospital, Research and Development, Ludhiana, India;
The exact positioning of tofacitinib in the therapeutic algorithm is still unclear. We evaluated the efficacy of tofacitinib in comparison to corticosteroids for induction of remission in patients with moderately active UC.
This was a randomized, parallel-group active-controlled pilot study comparing the efficacy and safety of corticosteroids and tofacitinib in inducing remission in adults with moderately active UC (defined as total Mayo clinic score 6-9). Patients were randomly assigned to receive corticosteroids (prednisolone, starting 40 mg daily and tapered by 5 mg every week over 8 weeks) or tofacitinib (10 mg twice daily) for 8 weeks. The primary endpoint was composite remission (defined as total Mayo clinic score≤2, with an endoscopic subscore of 0 and fecal calprotectin<100 mcg/g) at 8 weeks. Clinical remission (defined as Mayo clinic score ≤2) and clinical response (defined as a decrease of 30% in the Mayo clinic score from baseline or more and 3 or more points, along with either a rectal bleeding subscore of 0 or 1 or a decrease in the rectal bleeding subscore of 1 point or more) at week 8 were also evaluated. Follow-up assessments for efficacy and safety were done at weeks 2, 4, and 8.
Seventy-eight patients (mean age 37.78±13.94 years, 42[53.84%] males; 43 assigned to tofacitinib and 35 to corticosteroids group) were enrolled. At week 8, there was no significant difference in the proportion of patients achieving composite remission in the two treatment groups (7 of 43, 16.28% in the tofacitinib group versus 3 of 35, 8.57% in the corticosteroid group; p=0.31). Clinical remission at week 8 was achieved in 18 of 43(41.86%) patients receiving tofacitinib and 13 of 35 (37.14%) patients receiving corticosteroids (p=0.67). Clinical response was seen in 28 of 43(65.12%) and 25 of 35(71.42%) patients in the tofacitinib and corticosteroid groups, respectively(p=0.55). No difference was observed in the median number of days required to achieve symptomatic remission between the two groups (10[IQR 7-18.75] and 10[IQR 5-12.5] days for tofacitinib and corticosteroids, respectively;p=0.25). One patient in the tofacitinib and corticosteroid group discontinued treatment due to the development of pulmonary tuberculosis and pustular acne, respectively. Another patient receiving tofacitinib developed herpes zoster. No serious adverse events or major adverse cardiovascular events were observed.
In patients with moderately active ulcerative colitis, there is no difference between the efficacy and safety of tofacitinib and corticosteroids for induction of remission. Tofacitinib can be used as a first-line therapy for inducing remission in moderately active UC. (CTRI Registration number: CTRI/2021/10/037641)