Low-dose Methotrexate has Similar Outcomes to High-dose Methotrexate in Combination with Anti-TNF Therapy in Inflammatory Bowel Diseases.

BACKGROUND AND AIMS: Methotrexate [MTX] is a well-known immunomodulator in the treatment of inflammatory bowel disease [IBD] and is often combined with biologic agents. The ideal MTX dose for combination therapy has not been determined. This study aimed to investigate the effect of varying doses of MTX on efficacy and safety outcomes when used with anti-TNF agents in IBD. METHODS: This study included patients with Crohn's disease [CD] or ulcerative colitis [UC] receiving care between January 2005 and June 2018. Low-dose MTX was defined as ≤12.5 mg/week and high-dose as >12.5 mg/week. The primary efficacy outcome was a composite of need for IBD-related hospitalization or surgery, steroid initiation, or change of biologic agent within 1 year. Safety outcomes included side effects related to MTX, serious infections, malignancy, and need to discontinue MTX therapy within 1 year. Multivariable logistic regression models adjusting for relevant covariates were used to assess independent association between MTX dose and outcomes. RESULTS: Our study included 222 patients with IBD [163 CD, 59 UC]. Just under a third were receiving low-dose MTX [28%]. The primary efficacy composite outcome was noted in 75 patients [47%] in the high-dose MTX group compared with 23 patients [37%] in the low-dose MTX group [p = 0.15]. We found no significant associations between MTX dose and any side effect [odds ratio 1.59, 95% confidence interval 0.77-3.31, p = 0.21] or development of serious infections [odds ratio 1.19, 95% confidence interval 0.41-3.45, p = 0.76]. CONCLUSIONS: Low-dose and high-dose MTX combination therapy were equally effective, and no difference in infection or malignancy rates was observed.

Vedolizumab Therapy Is Associated with an Improvement in Sleep Quality and Mood in Inflammatory Bowel Diseases.

INTRODUCTION: Poor sleep, depression, and anxiety are common in patients with inflammatory bowel diseases (IBD) and associated with increased risk of relapse and poor outcomes. The effectiveness of therapies in improving such psychosocial outcomes is unclear but is an important question to examine with increasing selectivity of therapeutic agents. METHODS: This prospective cohort enrolled patients with moderate-to-severe CD or UC starting biologic therapy with vedolizumab or anti-tumor necrosis factor α agents (anti-TNF). Sleep quality, depression, and anxiety were measured using validated short-form NIH PROMIS questionnaires assessing sleep and mood quality over the past 7 days. Disease activity was assessed using validated indices. Improvement in sleep and mood scores from baseline was assessed, and regression models were used to identify determinants of sleep quality. RESULTS: Our study included 160 patients with IBD (49 anti-TNF, 111 Vedolizumab) among whom half were women and the mean age was 40.2 years. In the combined cohort, we observed a statistically significant and meaningful decrease in mean scores from baseline (52.8) by week 6 (49.8, p = 0.002). Among vedolizumab users, sleep T-score improved from baseline (53.6) by week 6 (50.7) and persisted through week 54 (46.5, p = 0.009). Parallel reductions in depression and anxiety were also noted (p < 0.05 by week 6). We observed no difference in improvement in sleep, depression, and anxiety between vedolizumab and anti-TNF use at week 6. CONCLUSIONS: Both vedolizumab and anti-TNF biologic therapies were associated with improvement in sleep and mood quality in IBD.