VIENNA — Vedolizumab can lead to endoscopic remission in some patients with moderately to severely active Crohn’s disease that hasn’t responded to previous therapy, according to the VERSIFY study (NCT02425111), which builds on the findings of the GEMINI 2 and 3 trials.
This study “confirms that vedolizumab is a first-line biologic option after conventional therapy,” said investigator Silvio Danese, MD, PhD, from Humanitas University in Milan.
In fact, after treatment with the monoclonal antibody, 12% of participants achieved endoscopic remission: 20% of participants not previously treated with a TNF inhibitor and 6% of participants previously treated with a TNF inhibitor.
Endoscopic remission, the primary study outcome, “is an important treatment target that can influence the course of the disease,” Danese said here at the European Crohn’s and Colitis Organisation 2018 Congress, where he presented 26-week results.
“These results, although numerically not impressive, at least in TNF-exposed patients, are very encouraging because the population of this study consisted of patients with refractory Crohn’s disease,” said Gerassimos Mantzaris, MD, PhD, from Evangelismos, Ophthalmiatreion Athinon, and Polyclinic Hospitals in Athens, who was not involved in the study.
“And, in contrast to anti-TNF agents, vedolizumab is a slow-acting drug,” he told Medscape Medical News.
In another presentation at the congress, Renáta Bor, MD, from the University of Szeged in Hungary, and her colleagues reported that vedolizumab is associated with mucosal healing. However, their study was different from VERSIFY in several ways: treatment duration was shorter; both Crohn’s disease and ulcerative colitis were assessed; and people who had previously failed TNF inhibitor therapy were included in the study population.
VERSIFY Study
The 101 participants in the phase 3b, single-arm, multicenter VERSIFY study received an open-label standard induction dose of intravenous vedolizumab 300 mg on day 1 and at weeks 2, 6, 14, 22, up to week 26, and underwent screening colonoscopy at weeks 14 and 26. A central reader performed the endoscopic evaluations.
At baseline, mean Simple Endoscopic Score for Crohn’s Disease (SES-CD) score was 16 — remission was defined as a score of 4 or below — and mean Crohn’s Disease Activity Index (CDAI) score was 324. Of the participants, 55% had failed previous treatment with a TNF inhibitor, 40% had very high levels of C-reactive protein — above 10 mg/L — and all had one or more mucosal ulcerations on ileocolonoscopy.
At week 26, complete mucosal healing, defined as an absence of ulceration, was achieved by 15% of the overall study population: 24% of participants not previously treated with a TNF inhibitor and 7% of participants who failed previous TNF inhibitor therapy.
“I am impressed with the results of the complete mucosal healing, as more patients achieved this secondary end point: 15% overall, which is marginally inferior to the other secondary end point — the drop in SES-CD score by at least 50%,” Mantzaris pointed out.
Clinical Remission
At week 10, clinical remission, defined as a CDAI score of 150 or below, was achieved by 36% of all patients; this rose to 42% at week 26. Again, those not previously treated with a TNF inhibitor fared better than those previously treated, with 52% of those not previously treated achieving clinical remission at week 26.
Table. Endoscopic Outcomes at Week 26
| Outcome | Overall, % (n = 101) | No Previous TNF Inhibitor, % (n = 46) | Previous TNF Inhibitor Failure, % (n = 55) |
|---|---|---|---|
| Remission | 12 | 20 | 6 |
| Response | 25 | 28 | 22 |
| Complete healing | 15 | 24 | 7 |
Complete mucosal healing varied by segment of the GI system. “The large bowel had a tendency to heal more than the ileum,” Danese reported.
In terms of safety and tolerability, there were no new safety signals. Sixty-six participants experienced an adverse event and 11 experienced a treatment-associated adverse event, including two exacerbations of Crohn’s disease. There were no cases of liver injury or death.
“I believe that the rate of endoscopic response, remission, and complete healing will be higher in patients who maintain clinical remission on vedolizumab at the end of 1 year,” Mantzaris said.
“We are awaiting the 52-week data,” Danese added. “I think they will be available soon.”
Prospective, real-life studies are needed to confirm the usefulness of vedolizumab in Crohn’s disease, as well as whether cotreatment with an immunomodulator can increase the efficacy of vedolizumab, Mantzaris said.
The VERSIFY study was supported by Takeda Pharmaceuticals International. Danese is a member of the Takeda advisory board. Mantzaris has disclosed no relevant financial relationships.
European Crohn’s and Colitis Organisation (ECCO) 2018 Congress: Abstract OP023. Presented February 16, 2018.
Follow Medscape Gastro on Twitter @MedscapeGastro and Damian McNamara @MedReporter
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