Subcutaneous golimumab induces and maintains clinical response in ulcerative colitis, according to two studies in the January issue of Gastroenterology.
In the first, Dr. William J. Sandborn of the University of California San Diego, and his colleagues, looked at 1,064 patients enrolled in the PURSUIT-SC study (Program of Ulcerative Colitis Research Studies Utilizing an Investigational Treatment–Subcutaneous), an integrated phase II and phase III study of subcutaneous golimumab.
Golimumab, developed by Janssen Pharmaceutical Companies of Johnson & Johnson – the sponsor of both studies in this month’s Gastroenterology – is a fully human monoclonal antibody to tumor necrosis factor–alpha.
All patients had an established diagnosis of UC and moderate to severe disease activity, defined as a Mayo score of 6-12, with an endoscopic subscore of at least 2.
Additionally, all patients had previously tried and failed oral 5-aminosalicylates, oral corticosteroids, azathioprine (AZA), and/or 6-mercaptopurine. Alternatively, they were simply unable to wean off corticosteroids.
Patients enrolled in the phase II, dose-finding portion of the study were randomized to subcutaneous injections of placebo or one of three different golimumab doses at weeks 0 and 2: 100/50 mg (i.e., 100 mg at week 0 and 50 mg at week 2), 200/100 mg, or 400/200 mg, respectively (n = 169).
"An additional 122 patients were enrolled while phase II data were being analyzed," wrote the authors.
"Clinical response" was defined as a decrease from baseline in the Mayo score of at least 30% and 3 or more points, accompanied by either a rectal bleeding subscore of 0 or 1, or a decrease from baseline in the rectal bleeding subscore of at least 1.
"Clinical remission" was defined as a Mayo score less than or equal to 2, with no individual subscore greater than 1.
Finally, "mucosal healing" was defined as a Mayo endoscopy subscore of 0 or 1.
The authors found that the median changes from the baseline Mayo score were –1.0, –3.0, –2.0, and –3.0 for placebo and golimumab 100/50 mg, 200/100 mg, and 400/200 mg, respectively.
Moreover, at week 6, a numerically greater proportion of patients assigned to golimumab 400/200 mg were in clinical response or remission, had mucosal healing, or had Inflammatory Bowel Disease Questionnaire (IBDQ) scores superior to that of placebo patients.
Next, after analysis of the dose-finding data, the 200/100–mg and 400/200–mg doses were selected for evaluation in phase III, a dose confirmation trial.
Overall, 774 patients participated in this portion of the trial, randomized to placebo, golimumab 200/100 mg, or 400/200 mg at weeks 0 and 2.
By week 6, significantly greater proportions of patients in the golimumab 200/100–mg and golimumab 400/200–mg groups (51.0%, and 54.9%, respectively) were in clinical response compared with patients assigned to placebo (30.3%; P less than 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," they added.
Looking at safety, nearly 40% of all phase III cohorts reported adverse events, most commonly headache and nasopharyngitis.
The most common serious adverse event – exacerbation of UC – was reported by 8 (1.1%) golimumab-treated and 8 (2.4%) placebo-treated patients.
A second study, also led by Dr. Sandborn, looked at whether continuous golimumab dosing would result in remission maintained to 1 year.
To that end, Dr. Sandborn next randomized the golimumab initial responders in the first study (n = 464) to placebo or injections of 50 or 100 mg golimumab every 4 weeks through 1 year.
Overall, 49.7% of patients in the 100-mg cohort maintained a clinical response through week 54, compared with 47% in the 50-mg group and 31.2% in the placebo group (P less than .001 and P = .010 for each dose versus placebo, respectively).
Remission was also seen with greater frequency among patients receiving 100 mg golimumab at both 30 and 54 weeks (27.8%) compared with placebo (15.6%; P = .004).
Finally, the proportion of patients with mucosal healing at both weeks 30 and 54 was significantly greater for patients receiving golimumab 100 mg (42.4%) compared with placebo (26.6%; P = .002). The mucosal healing rate for the 50-mg golimumab cohort was 41.7%.
Looking at safety, the authors did concede that "the proportions of patients who experienced at least one serious adverse event or discontinued because of an adverse event were greater for golimumab 100 mg compared with placebo or golimumab 50 mg."
However, "the duration of follow-up evaluation in the placebo group was notably shorter than either of the golimumab groups, and when adjusted for follow-up time, difference in the incidences of serious adverse events per 100 patient-years were less remarkable across treatment groups."