Jean-Frédéric Colombel1, Omoniyi J Adedokun2, Christopher Gasink3, Long-Long Gao3, Freddy J Cornillie4, Geert R D'Haens5, Paul J Rutgeerts6, Walter Reinisch7, William J Sandborn8, Stephen B Hanauer9. 1. Department of Gastroenterology, Icahn School of Medicine, Mount Sinai Medical Center, New York, New York. Electronic address: jean-frederic.colombel@mssm.edu. 2. Janssen Research & Development, Spring House, Pennsylvania. 3. Janssen Scientific Affairs, Horsham, Pennsylvania. 4. MSD International, Kriens, Switzerland. 5. Department of Gastroenterology, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands. 6. Department of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium. 7. Universitätsklinik für Innere Medizin III, Vienna, Austria. 8. Division of Gastroenterology and Department of Medicine, University of California, San Diego, San Diego, California. 9. Department of Medicine, Digestive Health Center, Northwestern University, Feinberg School of Medicine, Chicago, Illinois.
Abstract
BACKGROUND & AIMS: Among immunosuppressive- and biologic-naïve patients with moderately-to-severely active Crohn's disease (CD), a higher proportion of those treated with the combination of infliximab and azathioprine achieved corticosteroid-free remission at week 26 (CSFR26) than those given infliximab monotherapy; patients given the combination therapy also had higher serum concentrations of infliximab. Enhanced benefit of combination therapy may occur through synergistic modes of action or the influence of azathioprine on infliximab pharmacokinetics. METHODS: We analyzed data from 206 patients from whom week 30 serum samples were available: 97 received infliximab monotherapy (5 mg/kg, n = 97) and 109 received combination therapy (2.5 mg/kg/day; n = 109). Proportions of patients achieving CSFR26 and mucosal healing (absence of ulcers) at week 26 were calculated for each quartile of serum concentrations of infliximab, and exposure-response relationships were compared. RESULTS: Within quartiles of serum concentrations of infliximab, CSFR26 did not differ significantly between patients who received combination therapy vs monotherapy. However, among patients in the lowest quartile of serum concentration of infliximab, twice as many patients who received infliximab monotherapy achieved CSFR26 vs combination therapy. Anti-drug antibodies were detected only in the lowest quartile of serum concentrations of infliximab-in 35.9% of patients given monotherapy and 8.3% of patients given combination therapy. CONCLUSION: Among patients with CD and similar serum concentrations of infliximab, combination therapy with azathioprine was not significantly more effective than infliximab monotherapy. Combination therapy with azathioprine appears to improve efficacy by increasing pharmacokinetic features of infliximab. ClinicalTrials.gov, NCT00094458.
BACKGROUND & AIMS: Among immunosuppressive- and biologic-naïve patients with moderately-to-severely active Crohn's disease (CD), a higher proportion of those treated with the combination of infliximab and azathioprine achieved corticosteroid-free remission at week 26 (CSFR26) than those given infliximab monotherapy; patients given the combination therapy also had higher serum concentrations of infliximab. Enhanced benefit of combination therapy may occur through synergistic modes of action or the influence of azathioprine on infliximab pharmacokinetics. METHODS: We analyzed data from 206 patients from whom week 30 serum samples were available: 97 received infliximab monotherapy (5 mg/kg, n = 97) and 109 received combination therapy (2.5 mg/kg/day; n = 109). Proportions of patients achieving CSFR26 and mucosal healing (absence of ulcers) at week 26 were calculated for each quartile of serum concentrations of infliximab, and exposure-response relationships were compared. RESULTS: Within quartiles of serum concentrations of infliximab, CSFR26 did not differ significantly between patients who received combination therapy vs monotherapy. However, among patients in the lowest quartile of serum concentration of infliximab, twice as many patients who received infliximab monotherapy achieved CSFR26 vs combination therapy. Anti-drug antibodies were detected only in the lowest quartile of serum concentrations of infliximab-in 35.9% of patients given monotherapy and 8.3% of patients given combination therapy. CONCLUSION: Among patients with CD and similar serum concentrations of infliximab, combination therapy with azathioprine was not significantly more effective than infliximab monotherapy. Combination therapy with azathioprine appears to improve efficacy by increasing pharmacokinetic features of infliximab. ClinicalTrials.gov, NCT00094458.
Authors: Konstantinos Papamichael; Adam S Cheifetz; Gil Y Melmed; Peter M Irving; Niels Vande Casteele; Patricia L Kozuch; Laura E Raffals; Leonard Baidoo; Brian Bressler; Shane M Devlin; Jennifer Jones; Gilaad G Kaplan; Miles P Sparrow; Fernando S Velayos; Thomas Ullman; Corey A Siegel Journal: Clin Gastroenterol Hepatol Date: 2019-03-27 Impact factor: 11.382
Authors: John L Lyles; Aditi A Mulgund; Laura E Bauman; Weizhe Su; Lin Fei; Deepika L Chona; Puneet Sharma; Renee K Etter; Jennifer Hellmann; Lee A Denson; Phillip Minar; Dana M Dykes; Michael J Rosen Journal: Inflamm Bowel Dis Date: 2021-03-15 Impact factor: 5.325