Learn more about our FREE COVID-19 Patient Support Program for chronic illness patients and their loved ones.
Kelli Kobayashi is in pain. The 30-year-old physical therapist from Honolulu, Hawaii hasn’t had access to the weekly injection she takes for her rheumatoid arthritis (RA) in nearly a month — and her symptoms are starting to wear her down.
“My body is very achy and I have this general malaise,” Kelli says. “I have more pain in my hands and wrists, which is making it hard to get through my workday. I need my hands to work.”
Kelli, who has been living with RA for seven years, started taking the biologic medication called tocilizumab (Actemra) last year. This therapy blocks specific proteins in the immune system that play a role in the underlying inflammation that causes rheumatoid arthritis, an inflammatory or autoimmune disease that causes joint pain and other symptoms.
Actemra’s anti-inflammatory properties have also made it useful as a treatment for severe COVID-19. It received emergency use authorization from the U.S. Food and Drug Administration (FDA) last summer to treat COVID patients who are hospitalized with complications, such as requiring supplemental oxygen or mechanical ventilation.
Not long after, Actemra started becoming difficult for rheumatology patients to access. The drug’s manufacturer (Genentech), the FDA, the American College of Rheumatology, and others warned about it being in short supply.
CreakyJoints wrote about the shortage then, and we are covering it again now after hearing from patients like Kelli who are still or suddenly having trouble finding the medication.
Why Is Tocilizumab (Actemra) Still in Short Supply?
If the drug’s manufacturer and the FDA have known since August that Actemra was in short supply, it’s natural to question why this issue hasn’t been addressed yet. It’s been months since the issue emerged. Why can’t they just start making more of the drug?
The answer is something Genentech and other stakeholders in the system (medication distributers, pharmacy and health care systems, and government agencies) are actively and urgently trying to solve.
A major factor in the shortage initially was the Delta surge of COVID that began last summer. “This new wave of the pandemic has led to Genentech experiencing an unprecedented demand for Actemra IV [the intravenous version] well-over 400 percent of pre-COVID levels over the last two weeks alone and it continues to increase,” the company said in August, reported Endpoints News.
“Actemra shortages have been an unfortunate side effect of the pandemic and its efficacy in treating the catastrophic immune system overreactions to COVID-19,” says Andrew Concoff, MD, Executive Vice President and Chief Value Medical Officer of United Rheumatology, a national care management organization for rheumatology practices.
“Unfortunately, with the current surge and increase in hospitalizations there is demand for the drug,” Aretha L. Hankinson, Director, Media Relations for the American Society of Health-System Pharmacists (ASHP) told CreakyJoints.
But that’s not the whole story.
“I think it’s a general system failure,” says rheumatologist Shawn Baca, MD, who practices at Rheumatology Associates of South Florida and has several patients who are directly affected by the ongoing Actemra shortage. “It’s manufacturing; it’s shipping; it’s demand issues. Keep in mind: It’s not easy to make a biologic drug. It’s not like making a pill; you can’t just ramp up production overnight. These medications are very complex and take a long time to manufacture.”
Dr. Baca is also a doctor at the John Whelton Arthur Virshup CreakyJoints South Florida Arthritis Clinic, which provides free clinical care to underserved rheumatology patients.
Actemra IV vs. Injections: Both in Shortage
Actemra comes in two general formulations: an intravenous (IV) form that patients receive in an infusion clinic, doctor’s office, or hospital, and a subcutaneous self-injection form that patients can give themselves at home. (Which version is right for a given patient depends on personal preference, insurance coverage, and other factors. Some patients report that one version is more effective for them than the other.)
The IV version of Actemra is what is being used to treat hospitalized COVID-19 patients, so back in August, this was the formulation most at risk for being in short supply. Doctors and patients were encouraged to switch to the injectable version if there was concern about access to the IV Actemra.
As a result of this increased demand for injectable Actemra, it seems both versions are now in shortage for many rheumatology patients, depending on where they live and from which specialty pharmacy or health care provider they receive treatment.
Back in November 2021, Mayo Clinic rheumatologist John Davis III, MD, told MedPage Today that they were experiencing shortages of both kinds of Actemra. “Initially, this was mainly the IV formulation, but patients and physicians are reporting difficulty accessing the subcutaneous product,” Davis said. “This is affecting hundreds of patients in our practice.”
Rheumatologist Rachel Tate, DO, who practices in South Florida, says her practice is still experiencing Actemra shortages in both SC [subcutaneous] and IV formulations, adding “we are not the only teams in the area experiencing these shortages.”
However, not every doctor we spoke with cited Actemra shortages as a current problem for their patients. “At the moment, I have not heard of any recent issues of rheumatic patients not receiving either IV or SQ versions of Actemra,” Jeffrey Sparks, MD, a rheumatologist at Brigham and Women’s Hospital in Boston told CreakyJoints. He noted that part of the reason is that people hospitalized for COVID-19 are receiving baricitinib (a different medication that is also used to treat both rheumatoid arthritis and severe COVID) rather than tocilizumab (Actemra).
Angus Worthing, MD, a rheumatologist in the Washington, D.C. area, also reports that he and his patients have not experienced Actemra shortages, though they were bracing for them back in September.
Resolving the Actemra Shortage
On its website, Genentech says the following:
We continue to receive scheduled replenishments of Actemra, and are closely monitoring the supply situation. At this time, availability of Actemra SC and IV formulations continues to vary over time.
The dynamic nature of the pandemic, and factors such as potential variants and seasonal changes, has made supply planning complex and challenging to predict. Despite these challenges, we remain fully committed to returning to consistent, uninterrupted patient access to Actemra.
The company notes:
- We realize that all eligible Actemra patients’ needs may not be met during this time
- We also anticipate additional intermittent periods of stockouts in the months ahead if the pandemic continues at the current pace
- We are working to expedite replenishments and increase manufacturing capacity and supply wherever possible
- Actemra subcutaneous formulations (ACTPen® and pre-filled syringe) continue to be available for patients prescribed Actemra for FDA-approved indications, but will also be in limited supply through the authorized distributors
This means that Genentech can’t say for sure when the Actemra shortage will improve, but it is actively working to solve it.
Frustration and Fear for Patients on Actemra
Kelli’s rheumatologist mentioned several months ago that the drug could be in short supply, but the shortage didn’t affect her until just recently. Her pharmacy usually fills four weeks’ worth (four injections) of medication at a time. A few weeks ago, she says they could only fill two weeks’ worth. “Then they messaged me and said, ‘we’re having a shortage, we can’t get you medication now, we’ll notify you when we know when the next delivery is,” Kelli says.
She keeps calling the pharmacy, but they haven’t been able to provide any updates.
“My pharmacist told me to discuss other options with my rheumatologist. Since I have been responding well to Actemra, my doctor doesn’t recommend switching to another medication temporarily,” Kelly says. “He states that if I ever wanted to switch back to Actemra, it wouldn’t be as effective. Since I’ve ‘failed’ so many drugs before, I can’t just give up on this one. I feel like they are shifting responsibility to one another and that there’s no solution.”
Rabia Peeralia, who is a patient of Dr. Baca’s in Boca Raton, Florida, is also in a holding pattern with Actemra.
She was on a different RA medication for more than 12 years, which she says stopped working about two years ago. Though she tried many other medication types, Actemra was the only drug that she says made a difference for her. She tried a sample of the injectable form of Actemra last summer “and it was night and day,” she recalls. “I felt like I could climb a mountain or run a marathon. Most days I have to force myself to get out of bed.”
Rabia needs to get the medication from the Genentech Patient Foundation, which provides free medication to people who don’t have insurance coverage or who have financial concerns. With support from the CreakyJoints Clinic, Rabia applied and qualified to receive medication last fall, but was immediately put on a waiting list. She says she calls weekly to check in and is still waiting for Actemra to become available.
She is taking prednisone and tramadol to help manage the pain, but it’s not a long-term fix. “I already have a lot of damage to my joints,” says Rabia, 42, who was diagnosed with juvenile arthritis at 18. She’s worried about an uptick in symptoms and no treatment options in sight. “My ankles are swollen. My neck is in pain lately. I have pain in almost every joint.”
No Quick Fixes
Actemra is not a first-line drug for RA, which means that people typically take it after they’ve already tried numerous other medications that didn’t work for them or stopped working over time. This was the case for both Kelli and Rabia.
Dr. Concoff of United Rheumatology says that rheumatology practices have adjusted to the shortage by avoiding starting new patients on Actemra, attempting to get the medication when possible, and switching patients to alternative medications when necessary.
But all of these options have potential negative consequences for patients — and in some cases, there is no good Plan B.
Trying a Different Type of Medication
The thought of not being able to take a medication that is working well — and having to switch to a different one as a result — is upsetting and scary for Kelli.
“I don’t want to give up on Actemra and try something else,” she says, noting that she’s already been on a few other biologics, a JAK inhibitor, and several disease-modifying drugs for RA. “I’m only 30 and I will have to be on medication for a long time. There aren’t many other options left.”
Trying a Different Formulation
Another common option for dealing with the shortage is to switch patients from one formulation of Actemra to another — if, say, the IV is not available but the injection is, or vice versa. But this isn’t an ideal fix for everyone.
Deborah Constien, who has rheumatoid arthritis, was switched from IV to self-injectors months ago, but for her, “the self-injection is not nearly as effective” at controlling her symptoms. “There’s no end in sight,” she says, frustrated that “I can’t get [the formulation] that works best for me.”
Trying a Different IL-6 Medication
In other cases, doctors may recommend that patients switch to a different medication that works similarly to Actemra. Called Kevzara (sarilumab), it’s another biologic that works on the immune system similarly to Actemra. Both medications block an inflammatory protein called interleukin-6, or IL-6.
This can be a good option for some people, but it may not help everyone. Rabia says that she tried the other IL-6 inhibitor but it didn’t help her symptoms.
Why some biologics help some patients and not others — even in the same class — is still a mystery that doctors and researchers are actively studying.
“RA is different for each patient,” explains Dr. Baca. “Some do very well on drug A but not drug B. It comes down to individual genetics, specific differences in how the molecules work, and other things we don’t yet fully understand.”
When Actemra Is the Only Option
For certain other conditions, Actemra is the only good treatment option. This is the case for giant cell arteritis (GCA), a type of blood vessel inflammation whose only other treatment is long-term, high-dose steroids.
The Actemra shortage is “most acute and problematic” for patients with giant cell arteritis, Dr. Davis of the Mayo Clinic told MedPage Today, noting that steroids are “not a good option considering the increased risk of infectious complications, including more severe COVID-19 disease and related complications.”
Actemra is also used to treat cancer patients receiving a type of advanced immunotherapy treatment called CAR T-cell therapy. It can help prevent rare but possibly life-threatening reactions and is usually required by the FDA to be available on site during these cancer treatments in case such a reaction occurs.
But in guidance issued last month, the FDA lifted some requirements in place for patients receiving CAR T-cell therapy in light of the Actemra shortage. This includes requiring fewer doses of Actemra to be available in case of emergency and even encouraging health care providers to use their judgment in using CAR T-cell treatment in the first place, given the current Actemra shortage.
The COVID Factor
When some patients think about the big-picture reason the medication is in shortage — because it is being used to treat people hospitalized with severe COVID-19, who are largely unvaccinated — emotions run high.
“How is this even possible? This shouldn’t be happening,” says Kelli, who is fully vaccinated and boosted. “I did so as early as it was available to me since I’m considered higher risk and also a health care worker. I think it’s unethical that they can just stop our medications and that they’re being used to treat many people who choose to be unvaccinated instead.”
Kelli says she first reached out to CreakyJoints via Twitter to share her story and advocate for change. “I can’t work much longer like this.”
Rabia, who is also vaccinated, says, “I’m not upset that Actemra is being used for COVID, but I just wish there was more production. I hope they figure it out and get it to everyone who needs it.”
What to Do If You Can’t Get Actemra
Start by talking to your rheumatologist or doctor who prescribes Actemra and discuss your options. Each person’s case will be different and depend on their medical history, current symptoms, and other factors.
As Genentech told Kelli via Twitter, “we are working urgently to enable greater access to patients. We recommend patients work with their doctors for any questions they may have.”
Though the shortage will not be permanent — and access can vary considerably based on where you live — not everyone will be able to wait things out without treatment.
“I’ve been discussing all options with my patients, and focusing on the fact that we need to get their disease controlled for their overall health as opposed to waiting for the medication,” says Dr. Tate. “We do not know how long these shortages will last and we cannot risk their health further. Depending on the patient and their preferences, I may switch to another IL-6 or a different mechanism of action completely. Shared decision-making is the best option for making these tough choices.”
Back in August 2021, the American College of Rheumatology issued recommendations for doctors about how to deal with the shortage, which included:
- When the IV formulation is not available, substitute the subcutaneous form for the IV without any increased cost to the patient
- In the unfortunate situation where a treatment regimen must be altered due to a shortage, every effort should be made to provide treatment with a similar mechanism of action (i.e., another IL-6 biologic)
The ACR also urged insurance companies to insurers to make it easier for patients to switch medication formulations or types out of necessity, by exempting them from “prior authorization, step therapy protocols, and other utilization management practices so that they may more readily gain access to appropriate alternatives as determined by their rheumatologist or rheumatology health professional.”
In the context of the current shortage, we recommend discussing the following questions with your doctor and/or specialty pharmacist:
- Do you know when I can get access to Actemra again?
- Should I ration my Actemra injections by spacing out the doses so it lasts longer? (for people who currently have medication on hand)
- Should I switch from IV to injection or vice versa?
- Should I switch to the other IL-6 inhibitor, Kevzara?
- Should I try a different type of medication altogether — and if so, what are my best options?
- What are the risks of not taking any medication until I can take Actemra again?
CreakyJoints and the Global Healthy Living Foundation understand how upsetting and frustrating it is to be in this position. If you would like to share your concerns or story about accessing Actemra, please email Patient Advocate and Community Outreach Manager Zoe Rothblatt.
Genentech, which manufactures Actemra (tocilizumab), and Sanofi, which makes Kevzara (sarilumab), are sponsors of the Global Healthy Living Foundation. They do not provide input on the editorial content we publish.
Get Free Coronavirus Support for Chronic Illness Patients
Join the Global Healthy Living Foundation’s free COVID-19 Support Program for chronic illness patients and their families. We will be providing updated information, community support, and other resources tailored specifically to your health and safety.
American College of Rheumatology Update on Tocilizumab Shortages. American College of Rheumatology. August 17, 2021. https://www.rheumatology.org/About-Us/Newsroom/Press-Releases/ID/1160.
Brennan Z. Genentech’s Tocilizumab Shortage Due to Covid-19 Now Hits CAR-T Recipients, with FDA Offering Alternatives to Help. Endpoints News. December 13, 2021. https://endpts.com/genentechs-tocilizumab-shortage-due-to-covid-19-now-hits-car-t-recipients-with-fda-offering-alternatives-to-help.
Guiding Principles from the American College of Rheumatology for Scarce Resource Allocation During the COVID-19 Pandemic: Il-6 Inhibition. August 26, 2021. https://www.rheumatology.org/Portals/0/Files/Guiding-Principles-Scarce-Resource-Allocation-IL-6-Inhibition.pdf.
Henderson J. Patients Face Pandemic-Induced Tocilizumab Shortage. MedPage Today. November 4, 2021. https://www.medpagetoday.com/special-reports/exclusives/95451.
Interview with Andrew Concoff, MD, Executive Vice President and Chief Value Medical Officer of United Rheumatology, a national care management organization for rheumatology practices.
Interview with Angus Worthing, MD, Clinical Assistant Professor of Medicine at Georgetown University Medical Center in Washington, D.C.
Interview with Aretha L. Hankinson, Director, Media Relations for the American Society of Health-System Pharmacists (ASHP)
Interview with Jeffrey Sparks, MD, Assistant Professor of Medicine at Harvard Medical School
Interview Rachel Tate, DO, rheumatologist with Arthritis and Rheumatology Associates of Palm Beach, Florida
Interview with Shawn Baca, MD, rheumatologist at Rheumatology Associates of South Florida
Policy for Certain REMS Requirements During the Tocilizumab Shortage Related to the COVID-19 Public Health Emergency. U.S. Food and Drug Administration. December 2021. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/policy-certain-rems-requirements-during-tocilizumab-shortage-related-covid-19-public-health.
Tocilizumab Injection. Current Drug Shortages. American Society of Health-System Pharmacists. https://www.ashp.org/drug-shortages/current-shortages/drug-shortage-detail.aspx?id=744&loginreturnUrl=SSOCheckOnly.
Update on Actemra (Tocilizumab) Supply in the U.S. Genentech. January 12, 2022. https://www.gene.com/media/statements/ps_081621.