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Combination treatment with guselkumab (Tremfya) plus golimumab (Simponi) may hold an advantage over use of either agent alone for patients with moderate-to-severe ulcerative colitis, results from a phase IIa proof-of-concept study suggested.

In an intention-to-treat analysis involving 214 patients, clinical remission at 38 weeks -- defined as a Mayo score of 2 or less, with no individual subscore above 1 -- occurred in 43.7% of those who received the combination therapy followed by guselkumab maintenance, as compared with 22.2% of those taking single-agent golimumab all along (nominal P=0.006), reported Brian G. Feagan, MD, of Western University in London, Ontario.

Clinical remission rates using a modified Mayo score (stool frequency subscore of 0 or 1 not increased from baseline, rectal bleeding subscore of 0, and endoscopy subscore of 0 or 1 with no friability on endoscopy), were higher for the combination group (47.9%) at 38 weeks versus both guselkumab (31%; nominal P=0.033) and golimumab (20.8%; nominal P<0.001) monotherapy groups, he said during his presentation at the American College of Gastroenterology annual meeting.

Several other key outcomes at 38 weeks favored the combination strategy as well, when compared with guselkumab and golimumab, respectively (with most comparisons being nominally significant):

• Endoscopic normalization: 25.4% vs 15.5% and 6.9%
• Endoscopic improvement: 49.3% vs 32.4% and 22.2%
• Histologic remission and endoscopic improvement: 42.3% vs 21.1% and 13.9%

"If we're ever going to come to terms with IBD [inflammatory bowel disease], I don't think it's with monotherapy," Feagan said. "In combination therapy, physicians will often worry about economics; I think that's a surrogate for their actual concerns about infection."

In the study, infections occurred in 31% of the combination patients compared with 23.9% of the guselkumab patients and 31.9% of the golimumab patients, while the rate for serious infections was 2.8% in each of the three groups.

"It's easy to say it's too expensive, but we don't pay for the drugs, and the more effective therapies we have, the better the incremental cost-effectiveness," he added. "I don't think economics is the issue, I think the issue is safety, and we'll need large studies to sort that out, but we now have classes of drugs that are completely safe ... combining them shouldn't be such a problem."

Guselkumab, an interleukin-23p19 subunit antagonist, is being studied for the treatment of IBD, while golimumab, a tumor necrosis factor (TNF)-alpha antagonist, is approved to treat ulcerative colitis.

from the VEGA trial showed that the combination more effectively induced clinical response, remission, endoscopic improvement, and histologic-endoscopic outcomes compared with either alone at 12 weeks.

Sandra El-Hachem, MD, of the Allegheny Center For Digestive Health in Pittsburgh, who was not involved in this study, told 番茄社区 that "this proof-of-concept study is encouraging and exciting."

"It shows that we can achieve clinical, endoscopic, and histologic remission more effectively using combination anti-TNF and anti-interleukin-23 in biologically naive moderate-to-severely active ulcerative colitis patients for induction, then use monotherapy with anti-interleukin-23 for maintenance,​ without compromising safety," she added.

For their phase IIa, double-blind trial, Feagan and colleagues randomized 214 adults with moderate-to-severe ulcerative colitis 1:1:1 to golimumab alone, guselkumab alone, or a combination of the two, followed by maintenance guselkumab alone for 38 weeks.

Participants were naive to TNF-alpha inhibitors and were either intolerant or refractory to conventional therapy.

Mean age was 38, and 54% were men. The mean duration of ulcerative colitis was 4.9 years, mean full Mayo score was 8.8 (out of 12), and 41% were on corticosteroids at baseline.

Overall, 13.1% of patients discontinued treatment before 34 weeks. "The only apparent differences were in the golimumab arm, where there were more withdrawals due to unsatisfactory clinical benefit or patient preference," Feagan noted.

Rates of adverse events and serious adverse events were similar across groups.

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