Objectives: Despite limited data, methotrexate (MTX) is often used as primary maintenance therapy in pediatric Crohn disease (CD). We sought to assess the effectiveness of MTX as "initial" primary maintenance therapy in newly diagnosed mild/moderate pediatric CD and ascertain baseline predictive factors. Methods: Single-center 10-year retrospective review of newly diagnosed CD patients treated with MTX as primary maintenance therapy. We compared baseline characteristics of those patients with sustained response/clinical remission to those patients who escalated to anti-TNF therapy within 1 year. Pediatric Crohn Disease Activity Index (PCDAI) ≤ 10 defined remission. Results: We identified 65 patients (mean age, 11.8 years; 72 % male; mean ± SD PCDAI, 17.8 ± 10.5) who started MTX ≤4 months of diagnosis as their primary maintenance therapy. Initial therapy prior to MTX was corticosteroids (CS) (54/65), defined diet (4/65), and combination CS/diet (6/65). Oral dosing was used in 55%; mean dose was 11.4 mg/m 2 orally and 12.5 mg/m 2 subcutaneously. At 1 year, 36 of 65 (55%) were on MTX monotherapy, and of those, 32 of 36 were in clinical remission; 81% were in steroid-free remission for the year following induction. For the 36 patients on MTX at 1 year, 14 (39%) had gross mucosal healing (22% of the original cohort). Ten additional patients had mucosal improvement (37% of total healed/improved). Fifteen patients (23%) were early failures, transitioning to anti-TNF ≤4 months. Baseline PCDAI, hemoglobin, ESR, albumin, and route of administration were not predictive of outcome. MTX was well tolerated in our cohort, with only 1 patient stopping due to elevated aminotransferases. No patient required CD surgery in the 1-year follow-up. Conclusions: MTX may have a primary maintenance role in mild/moderate CD.
Inflammatory bowel disease (IBD) pathogenesis is thought to be induced by a mix of genetic susceptibility, microbial populations, and immune triggers such as infections. Severe acute respiratory syndrome coronavirus 2 (SARS-nCoV2) may have increased capacity to generate autoimmune disease as evidenced by known spikes in diseases such as type 1 diabetes mellitus. Public health interventions like masking and closures additionally created remarkable drops in typical viral infections, with remarkable shifts in influenza-like illness reporting in 2020. This study aims to evaluate the impact of SARS-nCoV2 and associated interventions on pediatric IBD presentation in New York City using records of new diagnoses at a consortium of 4 institutions between 2016 and June 2022. We fit time series model (autoregressive integrated moving average model) to monthly and quarterly number of cases of each disease for January 2016–March 2020 and forecast the period between April 2020 and June 2022. We note no decrease in ulcerative colitis (UC) or Crohn disease (CD) in the aftermath of historic low levels of overall viral illness, and statistically significant increases in CD diagnoses and elevation in UC diagnoses creating a trend suggesting overall increase in IBD diagnoses exceeding the baseline rate of increase. These data suggest a possible linkage between SARS-nCoV2 infection rates and subsequent pediatric IBD presentation.
SARS-nCoV2 may have increased capacity to generate autoimmune disease; multiple reports suggest increased risk of Type 1 Diabetes, and case reports suggest other autoimmune linkages. Inflammatory Bowel Disease (IBD) pathogenesis appears to be a mix of genetic susceptibility, microbial populations, and immune triggers such as infections. Given the perceived role of infection in pathogenesis, decreased incidence of all infections during the pandemic secondary to non-pharmaceutical interventions should decrease IBD incidence rates. The aim of this study was to evaluate the association between the Covid-19 pandemic and IBD presentation in NYC using data from new diagnoses at a consortium of institutions.
Using EMR systems all diagnoses at 4 collaborating institutions were retrieved from 2015-2021. We fit time series model (ARIMA) to the quarterly number of cases of each disease for January 2016-March 2020 and forecast the subsequent 21 months. We not only did not observe a decline in pediatric IBD secondary to absent viral illness, but noted a statistically significant increase in Crohn's Disease approximately 6 months after the initial 2020 COVID wave in NYC, and trends suggesting increases overall in IBD diagnoses above the existing trend towards increased disease presentation that pre-dated the pandemic. This data suggests that there may be a linkage between SARS-nCoV2 infection rates and subsequent pediatric IBD presentation, warranting further evaluation in the aftermath of the Omicron wave.
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