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P325 Unfavorable initial thiopurine response does not reduce anti-drug antibody formation compared to thiopurine responders in Crohn's disease patients treated by thiopurine & infliximab co-therapy

H. Bar-Yoseph1, R. Almog2, B. Ungar3, S. Ben-Horin3, H. Yanai4, I. Dotan4, Y. Chowers5, M. Waterman*5

1Rambam Health Care Campus & Bruce Rappaport School of Medicine, Technion Institute of Technology, Department of internal medicine H, Haifa, Israel, 2Rambam Health Care Campus & Bruce Rappaport School of Medicine, Technion Institute of Technology, Department of Epidimiology, Haifa, Israel, 3Chaim Sheba Medical Center, Gastroenterology, Ramat Gan, Israel, 4Tel Aviv Sourasky Medical Center, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, IBD Center, Department of Gastroenterology and Liver Diseases, Tel Aviv, Israel, 5Rambam Health Care Campus & Bruce Rappaport School of Medicine, Technion Institute of Technology, Department of Gastroenterology, Haifa, Israel

Background

Previous studies demonstrated that combination thiopurine-Infliximab (IFX) therapy reduced the appearance of anti-drug antibodies (ADA) compared with IFX monotherapy. Whether the nature of past clinical response to thiopurine therapy affects this effect is unknown.

Table 1 Clinical and demographic parameters - all parameters were not significantly different between study groups except age at diagnosis (p=0.009)* and time of disease till IFX therapy (p=0.03)**

Table 1 Clinical and demographic parameters - all parameters were not significantly different between study groups except age at diagnosis (p=0.009)* and time of disease till IFX therapy (p=0.03)**

Monotherapy (n=61)Primary failure (n=22)Past responders (n=33)De-novo combination (n=20)
Female (%)49.245.536.455
Smoking (% never smoked)69.881.87068.4
BMI (Mean)22.421.420.921.4
Age at diagnosis (Median in years)*22.117.617.523.1
Time of disease till IFX therapy (Median)**5.659.32.8
Perianal disease (%)4663.642.445
Extra-intestinal manifestations (%)42.640.940.636.8
Past surgery (%)26.231.836.435

 

Methods

A retrospective multicenter cohort analysis of CD patients treated by at least four scheduled IFX infusions who had a documented response to past/ongoing thiopurine treatment and serial ADA measurements was conducted. Patients with combined therapy were grouped according to past response to thiopurine therapy (primary failure, past response and de-novo combination) and compared to IFX monotherapy. The primary end-point was ADA appearance. Kaplan-Meier (KM) analysis was used to compare ADA free survival between the groups.

Results

342 patients with serial ADA measurements were reviewed. 206 patients were excluded due to ineligibility to the study protocol: 73 received episodic IFX therapy, 25 received Methotrexate co-therapy, 16 did not have Crohn's disease, 32 did not receive IFX maintenance therapy and 60 had insufficient data. 136 were eligible for final analysis: 61 received IFX monotherapy, 33 responded to thiopurines, 22 failed thiopurines and 20 received de-novo combination therapy. No statistical significant differences were found between study groups in most demographic and clinical parameters (Table 1). However, Montreal B1 disease behavior was significantly more frequent in the primary failure group (p=0.015), patients on monotherapy were older at diagnosis (p=0.009) and IFX was started later during the disease for past responders (p=0.03). Median follow-up time was 272 days.

KM analysis revealed 2 year cumulative risk of ADA development of 31.8% in the thiopurine failures, 32.9% in the de-novo group, 24.4% in thiopurine responders and 62.0% in monotherapy group (p=0.013, p=0.012 and p=0.01 for the difference between each of the first 3 groups compared to monotherapy in Wilcoxon test, relatively) (Figure 1).

 

ECCOJC jju027 P325 F0001

“ADA-free survival curves between study groups”

 

Conclusion

Thiopurines-IFX co-therapy in CD patients is associated with reduced ADA formation relative to IFX monotherapy regardless of past response to thiopurines.

This study was partially supported by a generous grant from the Leona M. and Harry B. Helmsley Charitable Trust