The Unintended Consequence of the Overturn of Roe v Wade: Restrictions on Methotrexate Use

The recent Dobbs v Jackson Women’s Health Organization decision by the US Supreme Court not only limits reproductive options for our rheumatology patients but also has the unintended consequence of limiting treatment choices. Due to its embryotoxic potential, methotrexate (MTX), one of our most effective and heavily prescribed disease-modifying antirheumatic drugs, has come under scrutiny.

In 1985, Weinblatt et al published the results of their landmark clinical trial demonstrating the efficacy of low-dose MTX for the treatment of rheumatoid arthritis (RA).1 Since then, MTX has become the mainstay of therapy for RA and inflammatory arthritis. It is also an important tool in the treatment of other rheumatologic conditions such as systemic lupus erythematosus (SLE) and vasculitis. The most recent American College of Rheumatology guideline for the management of RA recommends MTX as the first-line medication for this disorder.2 In the US, as in most other countries, demonstration of MTX failure in patients with inflammatory arthritis is required prior to approving coverage for biologics and small molecules.

In addition to its use in rheumatic diseases, MTX provides a safe medical alternative to surgery for the treatment of ectopic pregnancies. Ectopic pregnancies occur in 1% to 2% of pregnancies and carry significant risk for maternal morbidity and mortality. Medical treatment includes a single dose of MTX 50 mg/m2 (80 mg for the average sized woman in the US) or multiple dosing (up to 4 doses of 1 mg/kg) over the course of 7 days.3 Both these regimens consist of significantly higher dosing of MTX than we use in rheumatology. Importantly, providers do not prescribe MTX for medical abortion. Medical abortion treatments rely on protocols that include administration of mifepristone followed by misoprostol. Nonetheless, because MTX inhibits trophoblast growth in ectopic pregnancies, providers and pharmacists, especially in states that have so-called trigger laws criminalizing abortion, have been hesitant to write and fill MTX prescriptions.

In response to this reluctance, the US Department of Health and Human Services issued a statement on July 13, 2022, prohibiting pharmacies from “making determinations regarding the suitability of a prescribed medication… and how to take them.”4 However, in the aftermath of the overturn of Roe v Wade, social media is exploding with patient accounts of pharmacists ignoring this decree and refusing to fill MTX prescriptions. Other patients report that their providers are no longer willing to write a prescription for MTX: “After 2 pharmacies refused to fill my methotrexate rx, I am now getting a message from my rheumatologists [sic] office that they won’t be prescribing methotrexate for me anymore bc it’s an abortifacient.”5

This interruption of MTX treatment is threatening the evidence-based standard of care for our patients with RA. Without early initiation of MTX therapy, patients with inflammatory arthritis will have delayed treatment, leading to greater disease activity, joint damage, loss of function, and, ultimately, more disability. Similarly, the recent tentativeness in prescribing MTX begs the question of what providers will do regarding teratogenic medications such as mycophenolate mofetil and cyclophosphamide. These particular medications are the backbone of treatment for SLE nephritis, a disease that predominantly affects reproductive-aged women. Thus, the very individuals who need these medications the most will be the most likely to be denied treatment.

In Bauchamp and Childress,6 core principles of medical ethics include respect for autonomy, beneficence, nonmaleficence, and justice. I would argue that using the Supreme Court’s recent ruling as a basis to deny access to MTX or other antirheumatic therapy disregards these tenets. When we restrict treatment choice, we violate our patients’ autonomy. Delaying access to standard of care contradicts the concept of beneficence. We are acting with maleficence when we do not prescribe medication that prevents disease progression, resulting in more disability and diminished quality of life. Finally, MTX is an affordable medication that patients with limited insurance or resources rely on to treat their diseases. If we reduce access to this medication, we will disproportionally affect those with the least resources, further exacerbating healthcare disparities and infringing on the concept of justice for all.

As rheumatology providers, we have an obligation to provide the best evidence-based care to our patients. MTX is an essential part of that care plan. There are steps we can take to ensure that when MTX is the best medication, treatment will continue. When possible, we should write the diagnosis and the indication for MTX therapy on the prescription. If necessary, we should speak directly with pharmacists who refuse to fill prescriptions. While these steps complicate already complicated workflows, we adjusted to such inconveniences during the hydroxychloroquine shortage amid the coronavirus disease 2019 (COVID-19) pandemic. We can adjust to inconveniences again. Importantly, we should ask our reproductive-aged patients repeatedly about their plans for pregnancy. If they are not planning pregnancy, we need to refer them to the appropriate resources for highly effective contraception.

One unresolved issue is what to do when our patients inadvertently become pregnant while taking MTX or other teratogenic medications. No contraception is 100 percent effective and unplanned pregnancies do occur. In the state of Texas where I reside, abortion is criminal even in pregnancies with teratogenic exposures that have a high risk of congenital anomalies. Currently, anti-abortion advocates are pushing to extend restrictions to make it criminal for Texans to obtain an abortion out of state. However, until that happens, I will continue to counsel my patients about all available reproductive planning options, including out-of-state pregnancy termination.

Copyright © 2022 by the Journal of Rheumatology

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