All subjects from the PURSUIT-SC trial program were eligible for enrollment into the PURSUIT-Maintenance (PURSUIT-M) study (Fig. 44.3) [11]. The 464 patients who achieved a clinical response with golimumab induction therapy were subsequently randomized to either placebo or treatment with 50 or 100 mg of golimumab administered every 4 weeks. A further 129 patients who had responded to placebo continued on placebo maintenance therapy, and 635 patients who did not respond (to either placebo or golimumab) received open-label golimumab 100 mg every 4 weeks (Fig. 44.4). The primary end point was clinical response maintained through to week 54. To demonstrate maintained response patients were assessed using the partial Mayo score at 4 weekly intervals with the addition of the endoscopic component (to generate the full Mayo score) at weeks 30 and week 54. Patients who met predefined criteria for a clinical flare at any time point underwent an endoscopy to confirm loss of response.

Golimumab was shown to maintain response in 47 % and 50 % of patients who received 50 or 100 mg golimumab every 4 weeks, respectively, versus 31 % in the placebo group (p = 0.010 and p < 0.001, respectively), thus meeting the trial’s primary endpoint (Fig. 44.5).

The secondary endpoint of clinical remission at both weeks 30 and 54 was achieved by 16 %, 23 %, and 28 % in the placebo , golimumab 50 mg, and golimumab 100 mg groups, respectively (Fig. 44.5). This difference reached statistical significance in the 100 mg group but not in the 50 mg group, despite a numerical advantage being seen (p = 0.122 and p = 0.004 for 50 mg and 100 mg golimumab-treated patients versus placebo). Additional secondary endpoints of MH, and corticosteroid-free remission by week 54 were also significantly more likely to occur in patients treated with golimumab compared with placebo.

Based on the results of PURSUIT-M, golimumab was approved by both the EMA and FDA . However, the dosing regimen approved by each differs slightly. In the USA, all patients receive 100 mg every 4 weeks, whilst in Europe patients below 80 kg receive 50 mg every 4 weeks and only those over 80 kg receive 100 mg every 4 weeks.

The design of PURSUIT-M was novel in several ways. Firstly, its definition of maintained response was more stringent than any previously seen in a UC trial. Long-term continuous efficacy was evaluated over the course of 15 prospective assessments without loss of response permitted at any time-point (Fig. 44.6). This compares with three assessments undertaken as part of the ACT-1 [9] maintenance trial or the two seen in the ACT-2 [9] and ULTRA [10] maintenance trials. Second, PURSUIT‐M was the first randomized withdrawal study of an anti-TNF in UC, thus clarifying that induction only is insufficient to maintain a long-term response.

It remains too early for any safety registry data for golimumab in inflammatory bowel disease to mirror the results from the infliximab (TREAT [12]) and adalimumab (PYRAMID [13]) registries. However, safety analyses from the PURSUIT trials and results as well as long-term extensions of randomized controlled trials carried out in rheumatoid diseases help to inform this area [14]. During the PURSUIT trial program the observed safety signals were reassuring and consistent with experience gained from use in rheumatoid arthritis as well as with the safety profile of the other anti-TNF agents. Four cases of tuberculosis were seen, all in golimumab-treated patients (who were also receiving corticosteroids) living in endemic regions, with one resulting death. This finding should serve to underscore the importance of robust pretreatment screening for tuberculosis in clinical practice. Overall, the percentage of patients with adverse events were similar across the golimumab treatment groups but were somewhat higher compared with the placebo group. However, when the safety data were normalized to 100 years of patient follow-up, the incidence of adverse events was comparable across each of the treatment groups (Table 44.1). The most commonly observed adverse events (other than UC flare) were nasopharyngitis, headache, and arthralgia. Injection site reactions were more common in golimumab treated patients and occurred in 7.1 % of patients receiving 100 mg golimumab, 1.9 % receiving 50 mg golimumab and 1.9 % receiving placebo. Other than this finding, no significant dose-dependent accumulation of adverse events was seen.