Among patients/families who are not in denial about their inflammatory bowel disease, especially Crohn’s disease, an important discussion is the use of combination therapy.  This has been discussed on this blog before (see some links below).  More data on this subject has been published and again favors the use of combination therapy (V Grossi, T Lerer, et al. Clin Gastroenterol Hepatol 2015; 13: 1748-56).

This study collected data from 2002-2014 on 502 children who participated in a prospective multicenter study. This data was derived from an observational registry rather than a randomized trial, but likely reflects real-world experience with regard to newly diagnosed patients. The authors excluded those with prior biologic therapy and prior resectional surgery.

KEY FINDINGS:

• Children receiving combination immunomodulator (IM) treatment were more likely to have durable infliximab therapy at 1 year, 3 years, and 5 years.
• Greater length of concomitant IMs was associated with better durability.
• For patients who had IM > 6 months after starting infliximab (n=194), durability was 0.70 at 5 years compared with 0.55 for patients with IM <6 months (n=144), and 0.48 for those who did not receive IMs (n=135).
• In boys, methotrexate appeared to be superior to thiopurines (P<.01): 0.98 at 5 yrs compared with 0.58.  However, there were 60 males receiving methotrexate.  In the study, only 21 females received methotrexate which limited any conclusions.

Among patients who stopped IFX, the reasons included loss of response (n=61, 43%), hypersensitivity reaction (n=41, 29%), elective (n=25, 18%), lost to f/u (n=5, 3%), and other causes (10, 7%).

The “right” dose of methotrexate as a combination agent remains unclear.  There was a wide range of dosing schedules in this study.  It is worth observing that the COMMIT study in adults found no significant difference in adults who received methotrexate in addition to infliximab compared with those receiving infliximab monotherapy.

Take-home message: In this large pediatric observational study, the use of immunomodulators increased the likely durability of infliximab.  Given prior conflicting data (particularly with regard to methotrexate), even more studies are needed to determine exactly how useful combination therapy is and when monotherapy will suffice.  From my viewpoint, I worry much more about loss of efficacy to infliximab than I worry about medication adverse effects.  As such, I will continue to inform families that combination therapy appears to improve infliximab durability.

Related blog posts:

• Digging into the COMMIT Study | gutsandgrowth
• Methotrexate Dosing in Dual Therapy | gutsandgrowth
• Don’t be Fooled About Withdrawing… | gutsandgrowth
• Methotrexate Abstract: …vs. Oral Administration | gutsandgrowth
• Methotrexate -First Choice Immunomodulator? | gutsandgrowth
• Toronto Consensus: …Ulcerative Colitis | gutsandgrowth
• How Long Will Infliximab Work? | gutsandgrowth
• Durability of Infliximab in Pediatric Crohn’s Disease | gutsandgrowth
• Another Look at “Step-up” IBD Therapy | gutsandgrowth
• Marriage, Divorce and Separation with Anti-TNF Therapy …

Mount Washburn, Yellowstone