Auto-Injectable Methotrexate: New Treatment Option for RA

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Methotrexate has long been a cornerstone of therapy in rheumatoid arthritis. Two new, injectable methotrexate products may help some RA patients for whom oral methotrexate is not as effective or causes adverse effects.

Rasuvo and Otrexup are prefilled, auto-injection devices that allow patients to give themselves subcutaneous injections of methotrexate without having to use a separate syringe and vial. Benefits of these new products include convenience and ease, but the drawback is a much higher cost.

Rasuvo is a single-dose auto-injection device that comes in 10 different doses of methotrexate: 7.5, 10, 12.5, 15, 17.5, 20, 22.5, 27.5, and 30 mg. Otrexup is available in doses of 10, 15, 20 or 25 mg per 4 mL.

Oral’s Drawbacks

Typically, RA patients take 15 mg of oral methotrexate each week, although some need a lower or higher dose, says Bella Fradlis, MD, attending physician, Division of Rheumatology, at Montefiore Health System and Assistant Professor at Albert Einstein College of Medicine in New York.

“The oral preparation of methotrexate seems to be the ‘go-to’ given cost-effectiveness and convenient dosing,” she says. “However, not all patients are able to tolerate oral methotrexate equally well. Some patients experience gastrointestinal side effects, such as nausea or vomiting.”

Bioavailability of oral methotrexate may be only two-thirds of what is absorbed when the drug is injected subcutaneously.

Stomach problems are not the only possible drawback of oral methotrexate. “You don’t get as much effective absorption with oral methotrexate” as can be achieved with subcutaneous injection of the drug, says Jonathan S. Coblyn, MD, Director of the Center for Arthritis and Joint Diseases at Brigham and Women’s Hospital in Boston. “The reason we may go to injectable methotrexate is that you may lose potency as you increase the dose.”

Dr. Fradlis

Bioavailability of oral methotrexate may be only two-thirds of what is absorbed when the drug is injected subcutaneously, says Dr. Fradlis.

“There have been several studies comparing oral and subcutaneous methotrexate throughout recent years. Some have shown that clinical responses are significantly better in patients who are given subcutaneous methotrexate as compared to oral methotrexate,” she says. A 2008 study published in Arthritis & Rheumatism showed that 80% of patients taking subcutaneous methotrexate achieved an ACR20 response compared with 60% who took oral methotrexate.¹

Patients may experience injection site reactions, such as redness, swelling and pain, so they should alternate injection sites to minimize this risk, she says.

Higher Price Tag

Do RA patients need auto-injection devices for their methotrexate? Dr. Coblyn acknowledges the new products may be more convenient, but unnecessary. He has prescribed injectable methotrexate for some RA patients who don’t find effective absorption with the oral disease-modifying anti-rheumatic drug (DMARD), and shows them how to draw the drug from vials with syringes they buy in bulk. “I have never had a problem with the drug in that form. We show them how to do it, and it’s easy.”

However, prefilled auto-injection products may be more convenient and easy to use, says Dr. Fradlis.

“Many of our patients have difficulty drawing up medication from a vial and self-administering subcutaneous metho­trexate” due to RA hand involvement or aging, she says. “They may need help with administration, which may not always be available. This may lead to non-compliance as well as frustration,” she says. Auto-injections may be simpler and quicker, she says.

Dr. Coblyn worries about higher costs for these new products. For example, four 25 mg doses of the auto-injected methotrexate range in price from $467–548, while a single 4 mL vial of generic methotrexate at a 25 mg dose costs $5.^2,3

“This is more expensive than the way we are doing it already. It may be a niche we needed to fill, but at what cost?” says Dr. Coblyn. Rheumatologists and their patients may look at various options, including splitting oral doses for better absorption or having someone help give patients injections, to achieve effectiveness and avoid the high cost, he says.

Susan Bernstein is a freelance journalist based in Atlanta.

References

1. Braun J, Kästner P, Flaxenberg P, et al. Comparison of the clinical efficacy and safety of subcutaneous versus oral administration of methotrexate in patients with active rheumatoid arthritis: Results of a six-month, multicenter, randomized, double-blind, controlled, phase IV trial. Arthritis Rheum. 2008 Jan;58(1):73–81.
2. The Medical Letter. 2014 March 31;Issue 1439.
3. GoodRx.