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P307 Safety, efficacy, and pharmacokinetics of golimumab in patients with moderately to severely Active ulcerative colitis: PURSUIT-SC long-term extension

W. Reinisch*1, P. Gibson2, W. J. Sandborn3, B. Feagan4, C. Marano5, R. Strauss5, J. Johanns5, H. Zhang5, L. Padgett5, O. J. Adedokun5, J.-F. Colombel6, J. Collins7, P. Rutgeerts8, D. Tarabar9

1Universitätsklinik für Innere Medizin III and McMaster University, Vienna and Hamilton, Austria, 2Alfred Hospital, Melbourne, Australia, 3University of California San Diego, Division of Gastroenterology, La Jolla, California, United States, 4Robarts Clinical Trials Inc., Robarts Research Institute, University of Western Ontario, London, Ontario, Canada, 5Janssen R & D, LLC, Spring House, Pennsylvania, United States, 6Mount Sinai, Icahn School of Medicine, New York, New York, United States, 7Oregon Health Sciences University, Department of Gastroenterology, Portland, Oregon, United States, 8University Hospital Gasthuisberg, Department of Haematology, Leuven, Netherlands, 9Military Medical Academy, Department of Gastroenterology and Hepatology, Belgrade, Serbia

Background

To evaluate safety and efficacy thru 4 years (ie, Wk228) of SC GLM maintenance in patients (pts) with moderately to severely active UC.

Methods

Amongst 1354 patients randomised and treated in induction, 1 228 were enrolled into maintenance. Pts completing treatment thru wk52 and evaluation at wk54 were eligible to enter a study extension (LTE) for an additional 3 yr. Pts entered LTE at same GLM dose they received at the end of the main study. During LTE, PBO- or GLM 50 mg, pts could cross over to GLM 100 mg q4wks upon worsening of UC. GLM Pharmacokinetics (PK) and immunogenicity were evaluated during the LTE. Efficacy analyses are based on pts randomised to GLM at wk0 of maintenance who continued GLM during LTE. Safety analyses are based on all pts treated with GLM at any time from wk0 of induction thru wk228.

Results

In total, 672 pts entered LTE: 666 were treated (96 PBO, 93 GLM 50 mg, 477 GLM 100 mg). The majority of study agent discontinuations were in PBO, 83.3% vs 37.2% GLM combined. PBO pts at study unblinding were discontinued; the majority of GLM pts discontinued because of adverse events (AE) and unsatisfactory therapeutic effect. PK analysis showed that serum GLM concentrations were dose proportional and maintained over time in pts receiving GLM 50 mg 100mg q4w in the LTE. The number of patients positive for antibodies to GLM was 4.4% and 3.7% in the 50 mg and 100 mg, respectively. Efficacy analyses are based on observed data. At wk216, 99.3% of pts receiving GLM had physician global assessment (PGA) of 0/1; 77.6% had PGA of 0; 76.1% had an IBDQ score > 170. The proportion of pts not receiving corticosteroids (CS) thru wk216 was maintained (Table). Through Wk228, rates of AEs of special interest (eg, demyelination and TB) and malignancy remained comparable to wk54. There were 4 NMSC (3-GLM 100 mg and 1-GLM 50 mg), 2 lymphoma (both GLM 100 mg), and 7 solid tumours [5-GLM 100 mg, 2 -GLM 50 mg]). There were 9 deaths overall: 2 (previously reported) cardiac and respiratory insufficiency-[PBO], biventricular heart dysfunction-[GLM 50 mg] and 7 additional deaths: MI, gall bladder cancer, advanced rectal cancer, adenocarcinoma of the colon, sepsis, accidental nitrous oxide overdose, and massive aspiration post-colectomy, all GLM 100 mg.

Conclusion

These data continue to support a positive benefit/risk profile for GLM in the treatment of moderate-severe UC. GLM treatment for up to 4yr maintained clinical benefit with no new safety signals observed; safety profile was similar to that observed through wk54.

Table 1. AE summary per hundred patient years of follow-up in the PURSUIT SC-Maintenance study extension from wk0 of induction

“PURSUIT LTE”