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Johns Shelly, Regueiro Miguel, Searching for the Crystal Ball That Will Predict Response to Infliximab, Inflammatory Bowel Diseases, Volume 9, Issue 1, 1 January 2003, Pages 73–74, https://doi.org/10.1097/00054725-200301000-00012
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Infliximab (Remicade [Centocor, Malvern, PA, U.S.A.]) is the first monoclonal antibody to tumor necrosis factor approved by the Food and Drug Administration for the treatment of inflammatory and fistulizing Crohn's disease (CD). Despite impressive efficacy data from clinical trials and postmarketing experience, approximately 30% of CD patients do not respond to infliximab. Predicting response to infliximab would have clear clinical implications and would allow the physician to better tailor treatment and avoid administration to patients with no chance of response. Better definition of genotype–phenotype profiles is an important step in defining all of inflammatory bowel disease (IBD) and potentially predicting response to medications. Serologic markers, specifically antisaccharomyces cerevisiae antibodies (ASCA) and perinuclear antineutrophil cytoplasmic antibodies (pANCA), may have a role in characterizing (phenotyping) patients with IBD, but the utility in predicting response to therapy has been largely untested.
In the current study, Esters et al. evaluated the utility of ASCA and pANCA in predicting the response to infliximab in patients with CD. There were 279 patients with active CD (89 fistulizing and 190 refractory luminal disease) included in an expanded access program for treatment with infliximab. Patients with refractory luminal disease received a single infusion of infliximab (5 mg/kg), and patients with fistulizing disease received three doses (0, 2, and 6 weeks). The Crohn's Disease Activity Index, serum C-reactive protein, and ASCA and pANCA assays were obtained in all patients at the first screening visit before inclusion in the trial and then at week 4 (refractory luminal disease) and week 10 (fistulizing disease) after first infusion. Response was considered complete if the Crohn's Disease Activity Index dropped to less than 150 (refractory luminal) or there was complete cessation of fistula drainage (fistulizing disease), and response was considered partial if the Crohn's Disease Activity Index decreased by more than 70 or there was a decrease in 50% of the number of draining fistulas. Of the 279 patients studied, 211 patients (76.0%) were responders, 59 (21.0%) were nonresponders, and 9 (3.0%) could not be evaluated because of confounding factors. The number of responders and nonresponders were similar in both the refractory luminal (79.0%, 21.0%) and fistulizing (75.0%, 25.0%) subgroups. From the total 270 patients analyzed, 129 (48.0%) were ASCA+ and 23 (9.0%) were pANCA+. Results revealed no significant relationship between response to treatment and serologic marker status either alone, in combination in the total group, or in the fistulizing/refractory luminal subgroups. However, ASCA−/pANCA+ patients in the refractory luminal subgroup showed a trend toward nonresponse (p = 0.067), whereas all ASCA−/pANCA+ patients in the fistulizing group were responders. In all groups, a significant drop in C-reactive protein was seen in those who responded to infliximab compared with no significant change in nonresponders.
