Abhinav Vasudevan1,2, Ajay Raghunath3, Shane Anthony3, Cian Scanlon4, Miles P Sparrow5, Peter R Gibson5, Daniel R van Langenberg4,3. 1. Department of Gastroenterology and Hepatology, Eastern Health, Box Hill Hospital, Level 2, 5 Arnold Street, Box Hill, VIC, 3128, Australia. abhinav.vasudevan@monash.edu. 2. Eastern Health Clinical School, Monash University, Box Hill, VIC, 3128, Australia. abhinav.vasudevan@monash.edu. 3. Eastern Health Clinical School, Monash University, Box Hill, VIC, 3128, Australia. 4. Department of Gastroenterology and Hepatology, Eastern Health, Box Hill Hospital, Level 2, 5 Arnold Street, Box Hill, VIC, 3128, Australia. 5. Department of Gastroenterology, Alfred Health, Monash University, Melbourne, VIC, 3004, Australia.
Abstract
BACKGROUND: The differential impact of anti-tumor necrosis factor (anti-TNF) therapy with methotrexate versus thiopurine co-therapy on endoscopic remission remains uncertain. AIMS: To compare rates of endoscopic remission based on methotrexate or thiopurine co-therapy used with anti-TNF therapy in Crohn's disease. METHODS: A retrospective observational study at two tertiary centers between 2010 and 2016 compared endoscopic remission rates and persistence on anti-TNF therapy in combination with methotrexate versus thiopurines for at least 3 months. RESULTS: Of 412 patients on anti-TNF therapy, 278 (67%) received immunomodulator co-therapy for ≥ 3 months and 269 (65%) had complete data for analysis. Methotrexate was used in 77 (29%) and thiopurines in 192 (71%) patients plus either infliximab (156, 58%) or adalimumab (113, 42%), with median follow-up of 2.8 years. The methotrexate group had greater prior immunomodulator intolerance (62% vs 20%, p < 0.01). Endoscopic remission rates were higher in those treated with thiopurine compared to methotrexate co-therapy at 12 m (58% vs 17%, p < 0.01) and at last review (59% vs 40%, p = 0.03). Endoscopic remission rates were higher with thiopurines than methotrexate when combined with adalimumab (49% vs 6%, p < 0.01) but not with infliximab (65% vs 54%, p = 0.09). In multivariate analysis, thiopurine co-therapy, elevated baseline CRP, and therapeutic anti-TNF drug levels were each associated with longer persistence of co-therapy (each p < 0.05). There were no significant differences in adverse events, malignancy or infection rates. CONCLUSION: In this cohort, anti-TNF and thiopurine co-therapy resulted in higher rates of mucosal healing than methotrexate, the difference is most pronounced with adalimumab and conversely with low-dose methotrexate.
BACKGROUND: The differential impact of anti-tumor necrosis factor (anti-TNF) therapy with methotrexate versus thiopurine co-therapy on endoscopic remission remains uncertain. AIMS: To compare rates of endoscopic remission based on methotrexate or thiopurine co-therapy used with anti-TNF therapy in Crohn's disease. METHODS: A retrospective observational study at two tertiary centers between 2010 and 2016 compared endoscopic remission rates and persistence on anti-TNF therapy in combination with methotrexate versus thiopurines for at least 3 months. RESULTS: Of 412 patients on anti-TNF therapy, 278 (67%) received immunomodulator co-therapy for ≥ 3 months and 269 (65%) had complete data for analysis. Methotrexate was used in 77 (29%) and thiopurines in 192 (71%) patients plus either infliximab (156, 58%) or adalimumab (113, 42%), with median follow-up of 2.8 years. The methotrexate group had greater prior immunomodulator intolerance (62% vs 20%, p < 0.01). Endoscopic remission rates were higher in those treated with thiopurine compared to methotrexate co-therapy at 12 m (58% vs 17%, p < 0.01) and at last review (59% vs 40%, p = 0.03). Endoscopic remission rates were higher with thiopurines than methotrexate when combined with adalimumab (49% vs 6%, p < 0.01) but not with infliximab (65% vs 54%, p = 0.09). In multivariate analysis, thiopurine co-therapy, elevated baseline CRP, and therapeutic anti-TNF drug levels were each associated with longer persistence of co-therapy (each p < 0.05). There were no significant differences in adverse events, malignancy or infection rates. CONCLUSION: In this cohort, anti-TNF and thiopurine co-therapy resulted in higher rates of mucosal healing than methotrexate, the difference is most pronounced with adalimumab and conversely with low-dose methotrexate.
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