Pipeline Medications for Ulcerative Colitis (Part 1) & Face Mask Shortages

Before getting to today’s post, I wanted to provide a link on why we are desperately short of face masks in the midst of this crisis: NY Times: How the World’s Richest Country Ran Out of a 75-Cent Face Mask

An excerpt:

The answer to why we’re running out of protective gear involves a very American set of capitalist pathologies — the rise and inevitable lure of low-cost overseas manufacturing, and a strategic failure, at the national level and in the health care industry, to consider seriously the cascading vulnerabilities that flowed from the incentives to reduce costs…

Given the vast global need for masks — in the United States alone, fighting the coronavirus will consume 3.5 billion face masks, according to an estimate by the Department of Health and Human Services — corporate generosity will fall short. People in the mask business say it will take a few months, at a minimum, to significantly expand production…

Hospitals began to run out of masks for the same reason that supermarkets ran out of toilet paper — because their “just-in-time” supply chains, which call for holding as little inventory as possible to meet demand, are built to optimize efficiency, not resiliency.

My take: Conserve, conserve, conserve PPE -supply chains meeting the need is NOT imminent.

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Several articles from Gastroenterology highlight emerging medications for ulcerative colitis (UC).

Two of the studies:

  • WJ Sandborn et al. Gastroenterol 2020; 158: 550-61.
  • WJ Sandborn et al. Gastroenterol 2020; 158: 562-72.

The first study was a phase 2 randomized trial of etrasimod which is an oral selective sphingosine 1-phosphate receptor modulator.  A total of 156 patients were randomized into 3 groups: placebo, 1 mg etrasimod, and 2 mg etrasimod.

Key findings (graphical abstract):

In the second phase 3, double-blind, double-dummy study, Sandborn et al show that, after the initial 2 intravenous doses,  among patients with an initial response subcutaneous vedolizumab (108 mg every 2 weeks) had similar effectiveness to intravenous vedolizumab (300 mg every 8 weeks); both SC and IV vedolizumab resulted in higher clinical remission rates compared to placebo at 52 weeks in the 216 patients: 46.2%, 42.6%, and 14.3% respectively.

Full text link: Efficacy and Safety of Vedolizumab Subcutaneous Formulation in a Randomized Trial of Patients With Ulcerative Colitis

Methotrexate Abstract: Subcutaneous vs. Oral Administration

A recent abstract (Link: Gut doi:10.1136/gutjnl-2014-307964) indicates that there may be some advantages with subcutaneous methotrexate compared with oral administration, especially at the onset of treatment.

Here’s the abstract (thanks to KT Park for sharing this abstract on his twitter feed):

Efficacy of oral methotrexate in paediatric Crohn’s disease: a multicentre propensity score study

Background Oral methotrexate (MTX) administration avoids weekly injections, reduces costs and may improve quality of life of patients with Crohn’s disease (CD), especially children. Routes of administration have never been systematically compared in CD. We aimed to compare effectiveness and safety of orally (PO) versus subcutaneously (SC) administered MTX in paediatric CD.

Methods 226 children with CD treated with oral or subcutaneous MTX were included in a multicentre, retrospective 1-year cohort study (62% boys, mean age 13.8±2.8 years, 88% previous thiopurines). 38 (17%) were initially commenced on oral, 98 (43%) started subcutaneous and switched to oral and 90 (40%) were treated with subcutaneous only. Matching and ‘doubly robust’ weighted regression models were based on the propensity score method, controlling for confounding-by-indication bias. 11/23 pretreatment variables were different between the groups, but the propensity score modelling successfully balanced the treatment groups.

Results 76 children (34%) had sustained steroid-free remission with a difference that did not reach significance between the PO and the SC groups (weighted OR=1.72 (95% CI 0.5 to 5.9); p=0.52). There were no differences in need for treatment escalation (p=0.24), elevated liver enzymes (p=0.59) or nausea (p=0.85). Height velocity was lower in the PO group (p=0.006) and time to remission was delayed in the PO group (p=0.036; Fleming (0, 1) test).

Conclusions In this largest paediatric CD cohort to date, SC administered MTX was superior to PO, but only in some of the outcomes and with a modest effect size. Therefore, it may be reasonable to consider switching children in complete remission treated with subcutaneous MTX to the oral route with close monitoring of inflammatory markers and growth.

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