A recent study (W-J Lee et al. Inflamm Bowel Dis 2016; 22: 2410-17) offers a great deal of insight into changes in the use anti-Tumor Necrosis Factor Alpha (ant-TNF) therapy from 2009-2013 in patients ≤24 years. The authors utilized databases with about 180 million people and identified 11,962 patients with inflammatory bowel disease (IBD).
- 3300 of the 11,962 (27.6%) patients were treated with anti-TNF therapy.
- Top-down treatment: 1298 of 3300 (39.3%) were treated with top-down therapy which was defined as usage of anti-TNF therapy within 30 days of first IBD medication prescription. Interestingly, over the course of the study, there was a trend towards more top-down (versus step-up) therapy and shorter time to initiation of anti-TNF therapy. In 2009, 31.4% used a top-down approach compared with 49.8% in 2013.
- Top-down therapy is associated with lower rates of corticosteroid use.
- Infliximab dominant anti-TNF: infliximab was the anti-TNF in 89.2% of patients less than 12, 82.3% of patients 12-17, and 55.1% of patients 18-24. Adalimumab accounted for the vast majority of the other TNF users. Though, the authors note a trend towards increasing use of adalimumab in both adult and pediatric patients in a separate study (Park KT et al. Inflamm Bowel Dis 2014; 20: 1242-49)
- Cotherapy: thiopurines and methotrexate were used as cotherapy in 13.5% and 7.2% of top-down group compared with 54.8% and 14.6% respectively in step-up strategy.
- Drug therapy among non-TNF users: 25.4% (2199) received a thiopurine, 79.3% (6871) received a 5-aminosalicylate, and 2.3% (201) received methotrexate.
- Anti-TNF therapy discontinuation: Using top-down strategy 69.2% persisted on infliximab at 12 months and 56.8% persisted at 24 months. In comparison, using step-up approach with infliximab, it was 72.7% at 12 months and 64.0% at 24 months. The numbers were quite similar with all the anti-TNF agents indicating that step-up approach had significantly lower rate of anti-TNF discontinuation. The authors speculate that one factor could be use of cotherapy or possibly other adverse reactions.
The authors explain some of the limitations of their study in its reliance on databases, particularly with regard to misclassification. However, in my opinion, these limitations do not affect any of the trends that the authors are able to document.
My take: For most of my patients, I have preferred to continue to utilize cotherapy and/or step-up therapy because I think there is likely to be a more durable anti-TNF response. The fairly small differences in anti-TNF durability have huge implications for those who lose anti-TNF responsiveness given the limited treatment options.
Related blog posts:
- Should All Pediatric Patients with Crohn’s Disease … – gutsandgrowth
- One Proposal to Reduce Thiopurine Combination … – gutsandgrowth
- Rethinking top-down treatment GutsAndGrowth
- 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 …