Simponi (golimumab) blocks tumor necrosis factor (TNF), which plays an important role in causing abnormal inflammatory and immune responses.
Simponi is specifically indicated for moderately to severely active ulcerative colitis in patients who have demonstrated corticosteroid dependence or who have had an inadequate response to or failed to tolerate oral aminosalicylates, oral corticosteroids, azathioprine, or 6-mercaptopurine.
The recommended dose is a 200 mg subcutaneous injection at Week 0, followed by 100 mg at Week 2 and then maintenance therapy with 100 mg every 4 weeks.
The FDA approval of Simponi for ulcerative colitis was based on two multi-center, randomized, doubleblind, placebo-controlled clinical trials in patients > 18 years of age (Trials UC-1 and UC-2).
This was an induction trial conducted in patients with moderately to severely active ulcerative colitis (UC), defined as a Mayo score of 6 to 12, who were corticosteroid dependent and who had failed or were intolerant to prior therapies. This trial was conducted in two parts. In Part 1 (dose finding), patients were randomized to one of 4 treatment groups: 400 mg Simponi administered subcutaneously (SC) at Week 0 and 200 mg at Week 2 (400/200 mg), 200 mg Simponi SC at Week 0 and 100 mg at Week 2 (200/100 mg), 100 mg Simponi SC at Week 0 and 50 mg at Week 2 (100/50 mg), or placebo SC at Weeks 0 and 2. In Part 2 (dose confirming), 771 patients were randomized to receive either 400 mg Simponi SC at Week 0 and 200 mg at Week 2, 200 mg Simponi SC at Week 0 and 100 mg at Week 2, or placebo SC at Weeks 0 and 2. Simponi 100/50 mg SC was not evaluated in Part 2; its safety and effectiveness has not been established in UC. Concomitant stable doses of other therapies were allowed. A greater proportion of patients achieved clinical response, clinical remission and had improvement of endoscopic appearance of the mucosa at Week 6 in the Simponi 200/100 mg group compared with the placebo group. The Simponi 400/200 mg group did not demonstrate additional clinical benefit over the 200/100 mg group.
This was a randomized-withdrawal maintenance trial that evaluated 463 patients who achieved clinical response with Simponi induction and tolerated Simponi treatment. Patients were randomized to receive Simponi 50 mg, Simponi 100 mg or placebo administered subcutaneously every 4 weeks. Concomitant stable doses of other therapies were allowed. The primary endpoint was the percent of patients maintaining clinical response through Week 54. A greater proportion of patients maintained clinical response through Week 54 in the Simponi 100 mg group compared with the placebo group. Simponi treated patients in clinical response (which included the subset of patients in clinical remission) in Trial UC-1, were again assessed for clinical remission at Week 30 and Week 54. A greater proportion of patients had clinical remission at both Weeks 30 and 54 without demonstrating a loss of response at any time point through Week 54 in the Simponi 100 mg group compared with the placebo group.
Adverse events associated with the use of Simponi may include, but are not limited to, the following:
Simponi (golimumab) is a human IgG1k monoclonal antibody specific for human tumor necrosis factor alpha (TNFa). It was created using genetically engineered mice immunized with human TNF, resulting in an antibody with human-derived antibody variable and constant regions. Simponi is produced by a recombinant cell line cultured by continuous perfusion and is purified by a series of steps that includes measures to inactivate and remove viruses.
Sandborn WJ, Feagan BG, Marano C, Zhang H, Strauss R, Johanns J, Adedokun OJ, Guzzo C, Colombel JF, Reinisch W, Gibson PR, Collins J, Järnerot G, Hibi T, Rutgeerts P Subcutaneous Golimumab Induces Clinical Response and Remission in Patients with Moderate-To-Severe Ulcerative Colitis. Gastroenterology 2013 Jun 1. pii: S0016-5085(13)00846-9
For additional information regarding Simponi or ulcerative colitis, please visit the Simponi web page.