The Belgian SMART Study Evaluating the Use of Golimumab for Ulcerative Colitis — BE SMART  

Ulcerative Colitis Clinical Trial

Official title: One Year Outcome of Golimumab for Patients With Moderate-to-severe Ulcerative Colitis: a Retrospective Multi-centre Belgian Cohort Study

Status Active, not recruiting

Clinical Trial Summary

Ulcerative colitis (UC) is a chronic inflammatory condition causing continuous mucosal inflammation of the colon, which is accompanied by episodes of bloody diarrhoea and abdominal pain. Both infliximab and adalimumab have been used with success for moderate-to-severe UC refractory to conventional therapy. More recently, golimumab, another anti-TNF antibody, has been added to the treatment armamentarium.

In the multi-centre, double-blind, placebo-controlled PURSUIT trial, patients with moderate-to-severe UC randomized to induction therapy with golimumab (200-100 mg, or 100-50 mg at week 0 and 2) achieved clinical response, clinical remission and mucosal healing more frequent than patients randomized to placebo. In the PURSUIT maintenance trial, patients randomized to golimumab every four weeks (100 or 50 mg) maintained clinical response through week 54 significantly more often than patients randomized to placebo. Data on the use of golimumab in daily clinical practice are unavailable.

The aim of the retrospective Belgian multi-centre BE-SMART trial is to evaluate the mid-term outcome of golimumab in patients with moderate-to-severe colitis. The primary endpoint will be steroid-free golimumab continuation at week 26. Secondary endpoints will include (steroid-free) clinical remission, (steroid-free) clinical response, (steroid-free) mucosal healing, (steroid-free) complete mucosal healing hospitalization-free survival, and colectomy-free survival.

Clinical Trial Description

Ulcerative colitis (UC) is a chronic inflammatory condition causing continuous mucosal inflammation of the colon, affecting the rectum and a variable extent of the colon in continuity.1 Ulcerative colitis is characterised by a relapsing and remitting course. The aetiology is still unknown, but both genetic and environmental factors seem to be crucial. Ulcerative colitis primarily presents in late adolescence and early adulthood, although the diagnosis may be made at any age. Compared with the general population, the quality of life patients with UC experience is low across all dimensions of health.2;3

When deciding the appropriate treatment strategy for active ulcerative colitis one should consider the activity, distribution and pattern of disease.4 Golimumab has been recently indicated for the treatment of moderately to severely active UC in adult patients who have had an inadequate response to conventional therapy including corticosteroids and 6-mercaptopurine (6-MP) or azathioprine (AZA), or who are intolerant to or have medical contraindications for such therapies.5;6 Besides golimumab, also infliximab and adalimumab are indicated and reimbursed for the treatment of adults with UC.7-9

In the multi-center, double-blind, placebo-controlled PURSUIT trial, patients with established diagnosis of UC and moderate-to-severe disease activity were randomized to receive golimumab 200 mg followed by 100 mg, or 400 mg followed by 200 mg, or twice placebo with 2 weeks apart.5 At week 6, significantly greater proportions of patients in the golimumab 200/100 mg and golimumab 400/200 mg groups (51.8%, and 55.0%, respectively) were in clinical response than patients assigned to placebo (29.7%; P<0.0001 for both comparisons). The efficacy of both golimumab induction regimens was also demonstrated for the major secondary endpoints of clinical remission, mucosal healing, and improvement from baseline in the IBDQ score, all at week 6. In term of safety, similar proportions of patients reported adverse events through week 6 across groups (37.5%, 200/100 mg; 38.9%, 400/200 mg; and 38.2%, placebo).

In a study extension of PURSUIT, patients who responded to induction therapy with golimumab (n=464) were randomly assigned to groups given placebo or injections of 50 or 100 mg golimumab every 4 weeks through week 52.6 Patients who responded to placebo in the induction study continued to receive placebo, while non-responders in the induction study received 100 mg golimumab. The primary endpoint, clinical response maintained through week 54, was observed in 47.1% of patients receiving 50 mg golimumab, 50.6% receiving 100 mg golimumab, and 31.4% receiving placebo (P=0.010 and P<0.001, respectively). At weeks 30 and 54, a higher percentage of patients who received 100 mg golimumab were in clinical remission and had mucosal healing (28.6% and 43.5%) than patients given placebo (15.4% and 26.9%; P=0.003 and P=0.001, respectively) or 50 mg golimumab (23.5% and 41.8%, respectively). Data in daily clinical practice are currently unavailable.

Of note, infliximab requires an intravenous route, and should therefore be administered at the hospital. Altogether, with both transport and monitoring phases, this administration can last more than a half day. In addition, it can be logistically challenging for some patients to reach the hospital (long distance, difficult public transport, significantly altered health condition, …). Subcutaneous therapy can be administered at home and is therefore a very convenient alternative against absenteeism for patients with an active life (workers, students) as well as for patients with challenges in reaching the hospital. In a recent prospective survey in Switzerland, the majority of anti-TNF naïve patients with Crohn's disease preferred subcutaneous administration with either adalimumab (36%) or certolizumab pegol (28%) compared to intravenous infliximab (25%).10 The patients' decision in selecting a specific anti-TNF drug was influenced by ease of use (69%), time required for therapy (34%), time interval between application of the drug (31%), scientific evidence for efficacy (19%), and fear of syringes (10%). Golimumab can therefore be a relevant alternative to infliximab and adalimumab, and can improve these patients' adherence thanks to the lack of either interference with everyday life or hurdles in reaching the hospital, and the need of only one injection every four weeks.

Golimumab currently exists in a prefilled syringe and an auto-injector device (Smartject™). In the recent open-label, multi-centric, prospective GO-MORE study in patients with active rheumatoid arthritis, patients injected 50 mg subcutaneous golimumab once monthly for 6 months. Patients reported use preferences and auto-injector evaluations by questionnaire. Patient auto-injector ratings were favourable overall (e.g. ease of use, pain).11 A similar Belgian trial has been conducted in patients initiating golimumab for moderate-to-severe UC (SMART, ClinicalTrials.gov NCT02155335). In this trial, 100 patients with moderate-to-severe UC, who were either anti-TNF naïve or previously failed infliximab therapy, and previously did not perform self-injection for any indication, have been randomized (1:1) to start crossover therapy with two injections of 50 mg golimumab supplied in a prefilled syringe, and two injections of 50 mg golimumab supplied in an auto-injector device. The efficacy of golimumab therapy will not be evaluated in the SMART study, but this patient population is an ideal cohort to evaluate the short- and mid-term outcome of golimumab monotherapy in real life, and to compare these data with the PURSUIT clinical trial data. ;

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

• NCT number: NCT02914717
• Study type: Observational
• Source: Universitaire Ziekenhuizen Leuven
• Status: Active, not recruiting
• Phase: N/A
• Start date: September 2016
• Completion date: May 2018