FDA Strengthens Warnings for Xeljanz, Olumiant and Rinvoq

By Jill Tyrer | Sept. 3, 2021

The Food and Drug Administration has issued warnings about the use of tofacitinib (Xeljanz and Xeljanz XR) as well as baricitinib (Olumiant) and upadacitinib (Rinvoq). All three belong to a medication class called Janus kinase (JAK) inhibitors and are used to treat arthritis and other inflammatory conditions.

A large, randomized safety clinical trial compared the use of tofacitinib for rheumatoid arthritis (RA) with a different type of drug, called tumor necrosis factor (TNF) inhibitors. Results showed a higher risk of heart-related problems, including heart attack, stroke, as well as cancer, blood clots and death with tofacitinib than with anti-TNFs, according to the FDA’s announcement. As a result, the FDA will require a “boxed warning” on the package, its most serious warning.

But if you take one of these medications, don’t stop, doctors say. Not enough data is available to understand exactly how to interpret the announcement and who might be affected.

“There’s nothing in this that says there’s an urgent need to stop the drug, and people should absolutely not stop on their own without discussing with their rheumatologist,” says Eric Ruderman, MD, rheumatologist and professor of medicine at Northwestern University Feinberg School of Medicine.

Tofacitinib is approved to treat polyarticular juvenile idiopathic arthritis, psoriatic arthritis and rheumatoid arthritis, as well as ulcerative colitis. It is used off-label in certain cases for psoriasis and for hospitalized COVID-19 patients. Baricitinib and upadacitinib are each approved to treat RA.

Safety Trial

When it approved tofacitinib, the FDA required drugmaker Pfizer to conduct the safety trial in RA patients who were taking methotrexate to find out its risks for heart issues, cancer and infections. Trial participants were over 50 years old with at least one risk factor for heart disease. Researchers looked at two doses of tofacitinib — 5 mg twice a day, which is approved for RA treatment, and 10 mg twice a day.

The FDA earlier this year warned about an increased risk of blood clots and death only with a higher dose of tofacitinib. But with the conclusion of the trial, results show the risks are also increased with the lower dose. The FDA now will limit the use of these JAK inhibitors for use only in patients who have not responded adequately to TNF inhibitors.

The trial was designed as a “non-inferiority study,” trying to show that the risk of using tofacitinib was no higher than with TNF inhibitors. “Essentially, they didn’t meet that non-inferiority, so they weren’t able to say with certainty that Xeljanz was no worse than TNF [inhibitors] for some of these safety events,” Dr. Ruderman says.

Questions Remain

Rheumatologist Jasvinder Singh, MD, MPH, professor of Medicine and Epidemiology at University of Alabama, Birmingham, and director of rheumatology research at Birmingham VA Medical Center, is waiting for more information before drawing any conclusions about who should be concerned and to what extent. The study itself was not yet available.

“I’m an epidemiologist so I like looking at the numbers. That usually helps me in understanding what the true risk is. That’s why I’m a little skeptical about making any definitive conclusions,” he says. For example, a 52-year-old woman with hypertension and a 62-year-old man who smokes, has high cholesterol and diabetes, both fit the profile of those in the study. “But those are two very different profiles,” he explains. “So when we say cardiovascular risk factors, which ones, how many, how does that differ by age and sex?”

Plus, Dr. Ruderman adds, “having RA itself is a risk factor for cardiovascular events and blood clots and cancers. Is everybody high risk? We don’t know.”

Drs. Singh and Ruderman also want to learn more about the warnings for baricitinib and upadacitinib. Safety trials have not directly compared either of those to anti-TNFs, but because they work in the same way in the body that tofacitinib does, the FDA expects the same outcomes and extended the warnings to them.

“What [the FDA] said is they don’t have any data for Rinvoq or Olumiant, but since they’re kind of the same class with a similar mechanism, they don’t know that those don’t have the same issues, so they’re going to include the same kind of language in those labels as well,” Dr. Ruderman says.

Drug Options

Tofacitinib, approved in 2012, was the first JAK inhibitor approved to treat arthritis. Baracitinib followed in 2018, and upadacitinib the following year. They are seen as an alternative to biologics and are preferred by many patients because they are in pill form rather than injection or infusion.

Still, JAK inhibitors are not as widely prescribed for arthritis as other medications, including biologics, which have been around longer and have a more robust track record. Dr. Singh estimates about 10% of eligible patients use JAK inhibitors.

Several options are available if you and your doctor decide it’s a good idea to switch. But Drs. Ruderman and Singh are unlikely to advise their patients to make any changes until they have more information, they say.

“Until I see the final recommendations from the FDA and the data from the study on which they’re based, I don’t really know what to tell them, so I’m not going to change anybody’s medicine until I have more information,” Dr. Ruderman says.

What Should You Do?

If you take one of these medications, don’t stop taking it, but be aware of the warning, and reach out to your rheumatologist for guidance.

“All medicines have side effects even when used correctly as prescribed, but in general the benefits of taking a medicine outweigh these risks,” the FDA says in the statement. “However, if you are a current or past smoker, or have had a heart attack, other heart problems, stroke or blood clots in the past, you should tell your health care professional as these may put you at higher risk for serious problems with these medicines.”

The FDA recommends that you seek emergency care if you experience any of the following, which could be a sign of a heart attack, stroke or blood clot:

    • Discomfort in the center of your chest that lasts for more than a few minutes, or that goes away and comes back
    • Severe tightness, pain, pressure or heaviness in your chest, throat, neck or jaw
    • Pain or discomfort in your arms, back, neck, jaw or stomach
    • Shortness of breath with or without chest discomfort
    • Breaking out in a cold sweat
    • Nausea or vomiting
    • Feeling lightheaded
    • Weakness in one part or on one side of your body
    • Slurred speech
    • Drooping on one side of your mouth
    • Swelling of a leg or arm
    • Leg pain or tenderness, or red or discolored skin in the painful or swollen leg or arm

And tell your doctor if you experience any of these symptoms:

    • Swelling of lymph nodes in your neck, armpits or groin
    • Constantly feeling tired
    • Fever
    • Night sweats
    • Persistent or worsening cough
    • Difficulty breathing
    • Hoarseness or wheezing
    • Unexplained weight loss

Updated Sept. 5 with comments from Drs. Singh and Ruderman

Tonya Horton

Tonya Horton is a Chronic Strength Champion, which means she doesn’t just take control of her pain — she battles back.  Read to learn how Tonya has found ways to overcome her osteoarthritis.

I’ll never forget the surprised look on my new doctor’s face when she entered the examination room four years ago.

“I wasn’t expecting to see you,” she said. “Your X-rays show the knees of a 70-year-old woman.”

Yes, my osteoarthritis diagnosis was a surprise. But it shouldn’t have been. Osteoarthritis (OA) disproportionately impacts women — especially women of color. It isn’t uncommon for a Black woman like me to develop osteoarthritis, but this isn’t universally known.

That’s why I am dedicated to sharing my story to uplift other OA patients who may not know they have access to resources and the support of others who understand what they’re going through. I’ve turned this passion into conducting research on the inequities in patient care experienced by women of color. We still have a long way to go, but I’ve found that the more I can share my story, the better.

My journey through pain
Four years later, I have good days and bad days, but there are very few “no pain” days. To help reduce the bad days, I’ve found strategies to keep my pain in check. It’s a journey — but I do everything I can to take control of my pain so I can live life on my own terms.

My medication options are limited due to allergies, so I’ve had to learn complementary methods of pain management — a ton of which I learned through the Arthritis Foundation’s e-Books; my favorite is Coping & Comfort, which has a lot of firsthand advice from arthritis patients.

I’ve also found that stress can make my symptoms even worse, so one thing I started doing is meditating. Whether it’s a one-minute or five-minute meditation, I find taking a few minutes out of the day to reset can help ground me, take my mind off my pain or help me feel a little better after a sleepless night.

As another form of self-care, I practice yoga as often as I can. Hatha yoga, especially, has been great for my pain relief because it helps me move and stretch in ways I never could’ve imagined.

In addition to making tweaks to my daily routine, I had to make big lifestyle changes to accommodate my situation: I relocated to a single-story home to avoid using stairs and purchased an arthritis-friendly car to make my day-to-day easier.

Support from others
Right after my diagnosis, I was hesitant to open up about my arthritis to others — even to my family. It may seem backwards, but I found strength by first connecting with total strangers. I’ve found community through the Arthritis Foundation, and now I’m a member of their Patient Leadership Council. Talking about my story with others who “get it” has given me the confidence to talk to my family, friends and co-workers. There are Live Yes! Connect Groups in a lot of places, completely run by volunteers. People come together virtually and in person, when safe to do so, to share stories.

Another way I find support is through the new Vim app — a tool I wish I had when I was first diagnosed. Through the app, I’m able to focus on my physical pain while assessing my mental health as well. Mental health isn’t often top-of-mind when dealing with a physically debilitating disease like arthritis, and the app’s social networking component allows me to connect with even more people facing similar battles.

At the end of the day, my biggest mantra is I don’t have to sacrifice the fullness of my life because I have arthritis. For those living with a chronic illness, they sometimes reduce their life to the bare minimum, but I refuse to do that. I can, and do, live a full life with arthritis.

How to Find Trusted Arthritis Info

By Arefa Cassoobhoy, MD, MPH, Chief Medical Editor, VP Medical Affairs, Everyday Health Group

Hello everyone! My name is Dr. Arefa Cassoobhoy, and I’m honored to be the guest expert on Episode 41: “Finding Trusted Arthritis Info” of the Live Yes! With Arthritis Podcast. I’m an internal medicine doctor and the chief medical editor at Everyday Health, a digital health information site. My No. 1 priority in this role is for people like you to be well-informed as you make decisions and take action along your health journey each and every day.

The key in providing quality health information is to create content that’s useful, easy to read and interesting — and never boring! At Everyday Health, I work with a talented team of journalists and medical experts to produce articles, videos and infographics about a range of health topics, including the various types of arthritis. The content is up-to-date and grounded in evidence-based medical information and real-world patient and clinician experiences.

Aside from the Arthritis Foundation and Everyday Health, I know it can be challenging to find a  trustworthy health website. But online health information is valuable as you familiarize yourself with medical terms, understand how your body is or isn’t working properly, follow through with self-care and lifestyle changes, and even in helping you sort through your treatment options.

And because time with your doctor is usually limited, it’s necessary to be a savvy patient and come prepared with questions — and to leave ready to do some online homework to better understand what your doctor told you. Online health sites are a great source for this prep work and follow-up and, importantly, can also be a place to be inspired by other people’s stories and experiences.

During this episode, I share with Rebecca and Julie how to evaluate a health article for credibility and where to go to find the latest information about your type of arthritis. Some quick tips:

  • Look closely at the page. Is there a date on the article that allows you to see if the information is up-to-date?
  • Is it written and reviewed by qualified experts, and do they list their sources to show they’ve done their research?

Another key tip: If something sounds like an advertisement, it probably is. You may need to dig deeper by going to the About page of a website to find out if they are committed to educating the public about a health issue — or do they seem to be raising awareness about a product to sell? If you’re in doubt after a quick check, disregard the information and leave the site. It should be easy to tell that medical information is solid on your go-to trusty sites.

We also talk about how to find the latest research information about arthritis. Your doctor is the best place to start in terms of asking what online sources may be most relevant for you. Then when you dive in, there are some cool tricks on Google to focus your search and get to relevant scientific articles fast. For those of you who need to understand a specific research study, I also share tips on how to navigate and understand the various sections of a study. And depending on what kind of information you’re looking for, your best option could be to read expert-written “review” articles that doctors consult for information and practice guidelines on how to take care of a patient with a specific condition.

The most important thing to remember is that you don’t have to become a medical expert to take care of your health. With a few helpful tips, you can harness online sources to learn about your condition, which can lead to more productive and satisfying conversations with your health care providers and inspire and enable you to live a healthier life on your terms.

Take action today. Tune in to the podcast now.

July 2021 Arthritis News Roundup

The Arthritis Foundation is your trusted source for arthritis-related news and COVID updates that affect people with arthritis. Here’s a wrap-up of the headlines from this past month.

The Latest in COVID-19 News & Arthritis

Delta Variant Causing States & Counties to Consider Mask Mandates
The highly contagious Delta variant of COVID-19 is causing concern across the U.S. as some states are seeing an increase in cases and hospitalizations. Some areas are considering mask mandates again, especially indoors.

Stay up to date with your local health department guidelines and check the Arthritis Foundation’s website regularly for COVID-19 & Arthritis FAQs.

Fauci: Immune Compromised May Need COVID-19 Vaccine Booster
Dr. Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Diseases and the chief medical advisor to the president, says people who are immune compromised may need a COVID-19 booster vaccine. He stated that patients with transplants, undergoing cancer chemotherapy and people with autoimmune diseases who are on immunosuppressant treatments may all need a vaccine booster to increase antibodies to the virus, especially as the Delta variant continues to spread. He also said revised mask guidance by top health officials is under active consideration. Get the details.

Autoimmune Rheumatic Disease Does Not Influence Immune Response Against COVID-19
Despite suspicions that patients with autoimmune rheumatic diseases (AIRD) may have worse immune responses against COVID-19, research indicates that this patient population did not differ from the general population in protective antibody responses, according to a study published in Springer.

Vaccine Hesitancy for Some With Rheumatic Diseases Weighs Heavy

Despite guidance from the American College of Rheumatology, some patients with rheumatic diseases are still very concerned about getting the COVID-19 vaccine. Dr. Jeffrey Curtis, MD, MPH, a University of Alabama at Birmingham rheumatologist who leads the American College of Rheumatology COVID-19 vaccine task force, says the concerns are valid. However, the benefits to vaccination outweigh the risk of having severe COVID or the potential for disease flare. Read more.

For details on COVID-19 vaccine recommendations for people with arthritis, visit the Arthritis Foundation Care & Connect hub.

Study Suggests Lasting Immunity After COVID-19, With a Big Boost from Vaccination
After an infection with SARS-CoV-2, most people — even those with mild infections — appear to have some protection against the virus for at least a year, a recent follow-up study of recovered patients published in Nature suggests. What’s more, this and other research demonstrates that vaccinating these individuals substantially enhances their immune response and confers strong resistance against variants of concern, including the B.1.617.2 (Delta) variant. Read the study.

In Other Arthritis News

FDA & Arthritis Foundation Make OA Priority Discussion

The Arthritis Foundation partnered with the U.S. Food and Drug Administration (FDA) to host a workshop recently on developing new treatments with long-term benefits for OA. Learn more about what’s being done to tackle treatments for OA.

Taking a Step Toward Discovering the Cause of Joint Disease
A new study finds switches near GDF5 gene linked to knee osteoarthritis and hip dysplasia. This new information could lay the groundwork for targeted screenings and treatments. Read more.

AbbVie, Lilly Face Fresh Delays in FDA Approval for Expanded Use of Arthritis Drugs

JAK (janus kinases) inhibitors have come under the U.S. Food and Drug Administration’s scrutiny, after preliminary results from a safety trial of Pfizer’s JAK inhibitor drug earlier this year showed an increased risk of serious heart problems and cancer in patients. Learn more.

Association Between Psoriasis and RA
Mounting evidence suggesting an association between psoriasis and an increased risk of RA has underscored the need for prospective studies to enhance our understanding of the disease course and optimal treatments in patients who have both diseases. Read more.

Biologic Treatments Could Mitigate Psoriatic Arthritis Risk
A new study finds that treatment with biological disease-modifying antirheumatic drugs (DMARDS) for people with psoriasis may lower the incidence of developing psoriatic arthritis later. Learn more.

Low-Dose Steroid Use in RA May Still Cause Risk for Vertebral Fractures

A new study reports that patients with rheumatoid arthritis (RA) being treated with low-dose glucocorticoids are still at risk for increased vertebral fractures. Read the report.

Learn more about corticosteroids and arthritis.

3D-printed Knee Implants Could Cut Surgery Times and Improve Arthritis Treatment
Known as Tailored Osteotomy for Knee Alignment (TOKA), this treatment improves the operative procedure and fit of high-tibial osteotomy (HTO) plates used to realign a patient’s knee, making them more stable, comfortable and better able to bear weight than existing generic plates. Learn more about the technique and how it also simplifies HTO surgery, making operations quicker and therefore safer.


What chronic pain takes away, Vim gives back!

To kick off Arthritis Awareness Month in May, the Arthritis Foundation launched our new Vim app — a unique, personalized tool to help people with arthritis easily find resources they need to manage their pain. The app also helps keep track of conditions and treatments, set and achieve goals, and connect with others for tips and encouragement.

The app stems from input received from 40,000 survey respondents in the Foundation’s ongoing Live Yes! INSIGHTS study, which is summarized in our How It Hurts report. As Vim was being developed, we sought extensive feedback along the way — from arthritis patients, health care professionals and other experts in pain management.

The app helps users set SMART goals based on their own situations and needs; goals that are specific, measurable, attainable, relevant and time bound. Users can also get information and ideas on how to best manage chronic pain through a deep library of expert content in seven categories. Maybe best of all, Vim fosters a spirit of community with common experiences, bringing people together who listen and inspire each other to help make managing pain easier.

Fast-rising NASCAR driver Natalie Decker, who is an Arthritis Foundation Champion Ambassador — she grew up with arthritis and continues to battle its challenges — says Vim has helped her get into a meditation routine that puts her mind at ease, plus set physical goals like regular stretching exercises. She says: “I like that you can cheer on other people. That’s cool.”

Vim is made possible by Arthritis Foundation sponsors who believe it’s a great solution to help people with arthritis find their Yes.

A representative of Vim Inaugural Sponsor TYLENOL says:

“TYLENOL® is a proud partner of the Arthritis Foundation and an Inaugural Sponsor of the Foundation’s three-year plan to conquer pain. We have chosen to support Vim and the pain initiative because we believe in the power of encouragement and education as key tools in helping those who suffer from arthritis pain to lead fuller lives.”

A spokesperson for Flexion Therapeutics, another Vim Inaugural Sponsor, adds:

“As a company committed to bettering the lives of patients confronting painful osteoarthritis, Flexion Therapeutics is honored to support the Arthritis Foundation’s Vim app, which is a powerful tool aimed at helping patients with arthritis, including osteoarthritis, take both small and big steps in managing the chronic joint pain that debilitates so many with this disease.”

Joe Tolman, founder of HurtSkurt, Vim Participating Sponsor, says:

“Becoming a Partner with the Arthritis Foundation and being part of the launch of the pain initiative and Vim app was an absolute no-brainer for us. The goal of HurtSkurt® is to help people achieve pain relief in the most efficient way, and the goal of the Vim app is to help people suffering with arthritis manage their everyday pain. If we can help even one person per day to have a better day because our products, then we are doing something special.  We couldn’t be more excited to be a part of this project.”

Get started with Vim today. And see for yourself how much it can help give you back what chronic pain takes away.