We would like to thank Dr. Yamamoto for his comments. We agree that ADA is a useful therapy for maintaining post-operative remission in patients intolerant and/or unresponsive to IFX and AZA. We also share his opinion that candidate patients for anti-TNFα treatment in the post-operative setting are mainly those who are at high-risk for post-operative recurrence (POR) of Crohn's disease (CD), especially if they have truly failed thiopurines pre-operatively and are endangered in the long-term by a disabling course of disease and/or intestinal failure.1
Regarding the issues raised by Dr. Yamamoto we believe that early and timely applied biologic therapy is more effective in preventing than treating POR of CD.2 Biologics are more effective when given early during the course of CD and surgical remission is the ideal model to assess the preventive effect of any treatment on the POR of CD. We are afraid that due to the lack of sufficient data at the moment selection of ADA or IFX as first line treatment in the post-operative patient relies on personal experience and Dr. Yamamoto's opinion is highly respected. Our pilot study simply suggests that ADA is a valid therapeutic option both for the prevention and treatment of POR of CD.2
There are also very limited data regarding the duration of biologic therapy in the post-operative patient.3,4 In this respect, Sorrentino et al. studied 12 patients who were in endoscopic remission after being treated with IFX scheduled treatment for 24 months starting in the immediate post-operative period and showed that 10 patients developed endoscopic POR at 4 months after discontinuation of IFX. Re-treatment with lower doses of IFX (3 mg/kg) every 8 weeks restored and maintained endoscopic remission of CD for 1 year indicating that anti-TNFα therapy should probably be continued beyond 2 years post-operatively to maintain remission.3
Finally, regarding whether or not concomitant immunosuppressants enhance the efficacy of biologics in patients with POR of CD, there is only a small uncontrolled study that showed that combined treatment with IFX and low-dose oral methotrexate (10 mg/week) that started at 2 weeks after surgery was effective in preventing POR of CD for 2 years.5
To conclude, we agree with Dr. Yamamoto that large scale prospective, randomized, controlled studies are urgently needed to obtain robust data in order to tailor treatment to the individual patient in the post-operative period. Dr. Yamamoto's remarks point to some of the important unmet demands that these studies should address. Additional topics of interest may be non-interventional genetic, serologic, and biologic markers as well as imaging and histologic data to identify CD patients at high risk for POR who may benefit for timely applied intensive therapy in order to prevent POR.
Conflict of interest statement
GJM has received honoraria for lectures and/or advisory boards from Abbott Immunology, MSD, Astra-Zeneca, and Ferring.