P679 Anti-TNF de-escalation following a treat-to-target strategy with golimumab therapy intensification to reach continuous clinical response in ulcerative colitis: the In-Target GETAID trial

Abstract

Abstract Background Achieving deep and continuous remission with tight control could allow de-escalation in patients with UC. The in-TARGET study was a prospective two-phase trial in UC patients initiating golimumab (GLM), that aimed to determine the proportion of patients with continuous clinical response (CCR) and endoscopic remission (ER) after one year of treatment optimization strategy (phase 1); then to assess treatment de-escalation outcome in these patients (phase 2). Methods This was a multicentre prospective interventional study in GETAID centres. The study included adult patients with active UC (Mayo Score ≥6 with an endoscopic subscore ≥2), naive to biologics. In the first part of the study, patients received a conventional GLM regimen, depending on their weight (<80 kg; ≥80 kg). At week 10, primary responders continued with the standard maintenance regimen (50 mg or 100 mg/4 w) and non-primary responders had systematic treatment optimization (<80 kg, GLM 100mg/4 w; ≥80kg, introduction of an immunosuppressant) (Figure 1). In the second part of the study, patients in CCR and in ER (Mayo endoscopic score 0-1) at w 54, had treatment de-escalation: GLM discontinuation for patients receiving 50mg, and dose de-escalation to 50mg for those receiving 100mg. Results A total of 197 patients were included, mean duration of UC was 75.9 (± 95.3) months, the mean total Mayo score was 8.4 (± 1.7). At w 10, 14 patients had stopped treatment for failure, 83 (42.1%) had a primary response, and 100 (50.7%) non-primary responders had treatment optimization. At w 54, 95 (48.2%) patients were still on GLM; of these, 64 (32.5%) patients were in CCR and ER. At w 0 and 10, no factors were associated with CCR + ER at w54. Serum GLM levels after w10 were not associated with CCR and ER at w54. No patient developed anti-GLM antibodies between w0 and w54. Sixty patients participated in the second de-escalation phase of the study: in 18 GLM was discontinued, in 38 GLM dose was de-escalated from 100 to 50mg/4 w, and 4 patients refused dose de-escalation. At w 108, 34/56 (60.7%) patients were in CCR and ER, with no change in treatment. No factors were associated with w108 remission. At w108, 23 patients had relapsed: 4/18 (22.2%) among GLM discontinuations, 19/38 (50%) among patients de-escalated from 100 to 50 mg/4w. During follow-up, no colectomy was reported, and 14 severe non-UC related adverse events occurred (3 severe infections, 2 severe anaemias, and 1 rectal cancer). Conclusion One third of UC patients achieved a CCR with ER at one year with optimized GLM therapy. After de-escalation of GLM, 60% of remitters at one year maintained deep remission at two years. Anti-TNF de-escalation following a treat-to-target strategy could be considered in some UC patients.