The Methotrexate Shortage – What Can We Do Now?

January 30, 2024

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

Diseases and Conditions Patient Advocacy

Guide to living with rheumatoid arthritis: part 3

August 30, 2017

the prior authorization process: how medication get covered by your insurance company

If you’re reading this post, there’s a good chance you’ve just been diagnosed with rheumatoid arthritis (RA). In Part 1 of the Guide to Living with Rheumatoid Arthritis, we went over the symptoms, diagnosis, and treatment of rheumatoid arthritis. In Part 2 of the Guide to Living with Rheumatoid Arthritis, we went over expectations, how to break the news to your loved ones and your boss, as well as important topics like food, exercise, and lifestyle.

Now that you’re acquainted with RA, you may have realized that some of these medications are very expensive. In Part 3 of Guide to Living with Rheumatoid Arthritis I’ll be covering the way doctors prescribe medications, how health insurance pays for the cost of medications, and finally how they end up in your possession.

The Process

As we’ve discussed previously, to treat rheumatoid arthritis you need to fight fire with fire. In the case of RA, fire = a disease modifying anti-rheumatic drug or DMARD. This is a medication that puts the immune system back in-check and calms it down.

They’re are two kinds of DMARDs: conventional DMARDs and biologics. Conventional DMARDs like methotrexate are less complex and do not target a particular cytokine (type of inflammation). They tend to cost less and typically don’t need pre-approval from your insurance company. Fortunately, methotrexate is the gold standard for the treatment of rheumatoid arthritis.

Biologics are the second type of DMARDs. These medications are a lot more complex and they do target a specific cytokine. Biologics are typically used if there’s a good reason you can’t take a conventional DMARD or if they haven’t worked in the past. Sometimes a rheumatologist may use a biologic and a conventional DMARD at the same time because they work better together. Biologics come as self-injectable pens, prefilled syringes, and infusions (i.e., via an IV going into your veins).

Unlike conventional DMARDs, biologics are VERY expensive and do need pre-approval or prior authorization from your insurance company before starting the medication. This means your doctor needs to justify this medication to the insurance company.

Prior Authorization

You may have heard your doctor say, “I’m going to need to get a prior authorization”. A prior authorization is the process by which your doctor and his or her team will justify the use of the medication to your insurance company. It typically involves A LOT of paperwork and phone calls. Sometimes the process takes weeks to days, but sometimes it can take months. If this is your first biologic, it typically takes 2 – 3 weeks from the moment your doctor prescribes the medication to the moment you receive it. But again, every situation is different. This is just an average.

First, every single medical office does prior authorizations slightly differently. Let’s go through an example.

Getting started

Your doctor talks to you about the risks and benefits of a certain medication. If you consent to treatment, he or she will ask his assistant to start a prior authorization.
The assistant then gathers all your medical insurance information and starts filling out forms. There’s a different form for every medication and for every different insurance company. The assistant then sends your doctor’s last progress note stating why you should receive this medication. The package is then sent to your health insurance plan.
At this point, your health insurance plan will go over your case and decide whether they will approve the medication. The medical reviewers follow a strict set of guidelines set forth by the insurance plan.
Let’s say they don’t approve the medication. In some cases, your doctor could appeal their decision by speaking to a medical director at the insurance company. At times, they want more information or a written letter with supporting scientific papers. Sometimes this works and sometimes it doesn’t. If it does great! If it doesn’t your doctor may try to look into patient assistance programs if one is available or they may alter your treatment plan.

You’re approved!

Now let’s say the medication gets approved! The insurance company will contact your doctor’s office and let them know. Because these medications are so expensive, your local pharmacy will not carry them. They may need to go to a specialty pharmacy who will mail them to your house.

The assistant will alert your doctor and he/she will send the prescription to your pharmacy.
The specialty pharmacy then prepares the script and sets a delivery date with you.
The medication is then mailed to your house.
The process is a little different when it comes to infusible biologics. In this case, the medication will NOT be mailed to your house. Instead, once your doctor’s office obtains the prior authorization, the infusion team at your doctor’s office will call to set up an appointment. Sometimes, you may need to go to an infusion clinic or a hospital for treatment.

Now you see why prior authorizations take a long time!

Biologic medications

There are many types of biologic medications that work in all sorts of different ways, however, they are given in either of these forms:

Infusions
Self-injectables
Pills

If prescribed an infusion you will get the medicine at your doctor’s office, an infusion center, or a hospital. Treatment can range between 1-5 hours. The doctor’s office will give you the medication and bill your insurance.

If you’re prescribed a medication that is self-injected, the medication will be mailed directly to you. This may seem very daunting, however, many clinics have a team in place to help you through this process. In my clinic, we have a dedicated team that will help you inject the medication for the first time in a supervised setting. During that visit you can ask questions that you may have about the medication: how to store it, how to dispose of the syringes and/or pens, what to do when traveling with biologics, side effect, etc.

If you’re prescribed an oral biologic medication, then the medication will be mailed directly to your house and you would take it just like you would take any other pill, i.e., follow your doctor’s written instructions.

What if your insurance company does not want to cover the full cost of your medication or if you have a high deductible plan?

You should rest assured that there are several financial assistance options available if your insurance will not cover the full cost of the medication or if you have a high deductible plan. Mind you, this does not guarantee that you will qualify but you won’t know unless you try.

For Commercial Insurance Plans (Group, Individual, Exchange) not Medicare

Some commercial insurance companies let their customers use a copay assistance card issued by the pharmaceutical company to help with the cost of the drug. Call me old-fashioned, but in my experience, talking to an actual human being is much faster and effective than email or using a contact form. For more information call the appropriate phone number listed below. If your plan allows the use of a copay card, the drug can often be obtained at a much smaller charge.

For Medicare Plans

The same medication options and medication administration options are available if you have Medicare or a Medicare Supplemental Plan, except you CANNOT use a copay assistance card.

Depending on the type of Medicare/supplemental plan that you have, the coverage of in-office infusions or self-administered shots widely vary. They may cover the entire cost or only a portion of the medication. For example, if your doctor prescribed you rituximab, your insurance company may cover 80% of the cost of the medication, leaving you with 20% of the total bill. When a medication costs about $22,000, 20% is a lot!

It’s always advisable to contact the doctor’s office or Medicare to find the out-of-pocket costs before receiving any treatment to fully understand the potential costs.

Regardless if you have a Medicare, commercial health insurance plan or if you do not have any health insurance at all, you may still qualify for financial assistance if you cannot afford treatment. Pharmaceutical companies and other non-profit organizations have many options that can even cover the full cost of treatment.

If you have concerns or questions about the costs of your treatment, please speak to your doctor or the patient advocate in your doctor’s office.

Conclusion

I hope this guide to living with rheumatoid arthritis has been informative and that you learned some valuable information about your diagnosis. Here are a few final thoughts:

Please follow your rheumatologist’s management plan. If you have any concerns, about your symptoms or your medications, it’s always important to keep an open line of communication.
It’s important to tell all your different doctors about your new diagnosis and any new medications that you are taking.
Always carry an updated list of you medications in your wallet. You never know when someone may ask for it. The doctor in the emergency room may not have access to your doctor’s records at 2 AM.
Make sure that you regularly follow-up with your rheumatologist in clinic. Your doctor may need to adjust your medications and watch for any side effects or complications.
If you cannot make a follow-up appointment, please contact your doctor’s office at least 48 hours in advance and re-schedule.
Learn as much as you can about your condition.
Talk to your friends and your family about your condition. You’re not alone.
Stay positive, keep active, and keep smiling!

Please leave your comments or questions below.

Co-written by Jessica Chapman, MD and Ilene Leveston, Patient advocate

Edited by Jessica Farrell, PharmD