A retrospective study (H Bar-Yoseph et al. Clin Gastroenterol Hepatol 2017; 15: 69-75) indicated that thiopurine use before infliximab (IFX) was associated with the prevention of antidrug antibody formation in patients with Crohn’s disease.
The authors had 207 eligible patients which included 93 who received IFX monotherapy, 52 who received combination therapy after response to thiopurine, 34 who received IFX after lack of response to thiopurines (but continued with combination treatment), and 28 who received de novo combination therapy. The total number of patients followed in these centers is much higher, but they excluded those with episodic infusions and for other reasons that could affect their conclusions.
- Prior thiopurine therapy was associated with lower antidrug antibodies (ADA). At 1 year, past thiopurine responders had 19.3% ADA, past thiopurine failures had 16.1% ADA; both were much lower that the monotherapy rate of 46.6% The de novo combination group had a rate of 21.9% which did not reach significance.
- Interestingly, after the first 5 months, the de novo combination group did not develop further ADA but during the first 5 months the rate of ADA was quite similar to the monotherapy rate. This could be related to the notion that thiopurines may take 3-6 months to achieve full effect.
- Combination therapy (compiled) was associated with higher rates of clinical remission (58.8% vs 40.9%) and lower rates of active disease (8.8% vs. 21.5%).
Overall, this study showed high rates of ADA compared to many studies but the conclusions are similar to other published studies. It could be that many of those with positive ADA were lower antibody levels and that many of these levels may not be clinically significant. The study has limitations mainly related to being a retrospective study.
My take: This study supports the following:
- Combination therapy is more effective than monotherapy
- Using an immunomodulator before starting infliximab may reduce ADA formation more effectively than starting combination therapy de novo.
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