Introduction

Although other newer biologics are available, methotrexate remains a cornerstone treatment for rheumatoid arthritis today.

When the Shortage Began

The current shortage of methotrexate began in late 2022, according to the American Society of Health-Systems Pharmacists (ASHP). It was primarily caused by manufacturing delays and supply chain issues impacting several major methotrexate suppliers, including Pfizer, Teva, and Fresenius Kabi. This led to intermittent supply disruptions and backorders for both the injectable and oral forms of the drug.

The methotrexate shortage has been further exacerbated by increased demand for the drug during the COVID-19 pandemic. Rheumatoid arthritis patients have been seeking additional prescriptions to manage worsening pain and inflammation while staying home. This spike in demand made the limited supply even more scarce for those dependent on methotrexate.

Expected Duration of the Methotrexate Shortage

The exact end date of the methotrexate shortage is still unclear. Manufacturers have indicated the shortage could potentially last through much of 2023, depending on how quickly they can resolve the underlying manufacturing and supply issues.

According to the American Society of Health-System Pharmacists (ASHP), the shortage is expected to continue through at least June 2023 for injection formulations from suppliers like Fresenius Kabi and Hikma [1]. The timeline is less certain for oral formulations, with some manufacturers like Teva unable to provide estimates on resolution.

Ultimately, the duration of the methotrexate shortage is highly dependent on pharmaceutical companies bringing their manufacturing capabilities back to normal levels. Some progress is being made, with Accord Healthcare restarting production in late 2022 after facility issues [2]. However, until all manufacturers have fully resumed stable methotrexate production and replenished inventory, the shortage is likely to persist.

Impacts on Rheumatology Patients

The methotrexate shortage has had significant impacts on rheumatology patients who rely on the drug to manage their conditions. Many patients are reporting difficulty filling their methotrexate prescriptions as pharmacies face short supply. This forces some patients to skip doses or take smaller doses than prescribed, which can lead to increased joint pain, stiffness, and swelling as their condition flares up. One survey found that 76% of pediatric cancer centers had patients miss or delay methotrexate doses due to the shortage.

In some cases, rheumatology patients may be forced to switch to more expensive biologic drugs instead of methotrexate to manage their symptoms. However, these drugs can cost thousands of dollars per dose, resulting in much higher out-of-pocket medical expenses. The financial strain adds further hardship for patients already dealing with increased joint inflammation and pain from the lack of methotrexate.

Alternatives During the Shortage

With the methotrexate shortage, rheumatology patients and their doctors need to explore alternatives to manage symptoms. Some options include:

Other DMARDs (disease-modifying antirheumatic drugs) like sulfasalazine or leflunomide may be substituted, depending on the patient’s condition. These work in a similar way to methotrexate and can help control inflammatory arthritis.

Biologics like Humira (adalimumab) or Enbrel (etanercept) target specific parts of the immune system. They can be very effective for rheumatoid arthritis but are more expensive.

Corticosteroids like prednisone reduce inflammation and pain quickly. But long-term use can cause side effects, so they are typically used as a bridge until other treatments start working.

Lifestyle measures like rest, exercise, diet, and stress management may also help patients manage symptoms during the shortage. But they should not replace disease-modifying medications.

Ultimately, it is important to have a conversation with your physician to discuss your personalized treatment plan.

Efforts to Resolve the Methotrexate Shortage

There are ongoing efforts to improve the methotrexate supply and end the shortage as soon as possible. Major manufacturers like Teva and Mylan have been working to resolve the issues that led to the shortage at their facilities (source). Teva restarted production at one facility in November 2022, which has helped stabilize the supply somewhat.

The FDA has also worked to increase available supply by reaching agreements to import methotrexate from abroad. The regulatory agency is engaging with manufacturers around the world to facilitate greater imports to meet US demand (source).

In addition, the FDA has allowed compounding pharmacies to help close the gap by producing compounded methotrexate products. While compounded drugs carry greater risk, this temporary measure expands supply while issues limiting manufacturing persist.

Preparing for Future Shortages

To prevent shortages in the future, steps must be taken to improve the resilience of the pharmaceutical supply chain. According to the AMA, diversifying suppliers is key to avoiding disruptions when a single company faces manufacturing issues (AMA, 2023). The FDA also recommends increasing stockpiles and reserves of essential medications that are at risk of shortage (Shuman, 2020). Finally, end-to-end supply chain transparency and information sharing between manufacturers, wholesalers, pharmacies, and regulators can identify potential shortages earlier and mobilize responses (Pharma News Intel, 2023).

By taking a proactive, collaborative approach, the pharmaceutical industry can build a more resilient supply chain and ensure patients have access to vital medications during public health emergencies. Regulators must also be empowered to act quickly when shortages arise to minimize disruptions to patient care.

Conclusion

In summary, the methotrexate shortage that began in late 2022 has had significant impacts on rheumatology patients who rely on this critical medication. Patients have struggled to access their usual methotrexate doses, resulting in increased symptoms and reduced quality of life. Rheumatologists have worked hard to find alternatives, but options are limited. This highlights the importance of ensuring consistent supply and production of key medications.

Solutions require collaboration across the pharmaceutical industry and government regulators. Manufacturing and supply chain improvements are needed to prevent future shortages and ensure access. With luck this shortage will be resolved quickly, but work remains to build a more resilient prescription drug supply system.

There is hope the manufacturers will resolve the issues causing this shortage in the coming months. However, the impacts have shown the vulnerability of relying on just a few suppliers for essential medications. Rheumatology patients and providers will continue advocating for reliable access to the treatments they need.

Medical Disclaimer

This information is offered to educate the general public. The information posted on this website does not replace professional medical advice, but for general information purposes only. There is no Doctor – Patient relationship established. We strongly advised you to speak with your medical professional if you have questions concerning your symptoms, diagnosis