What to Do As FDA Increased Warnings for Arthritis Drugs

What to Do As FDA Increased Warnings for Arthritis Drugs

Millions of people suffer from various forms of arthritis. The Centers for Disease Control & Prevention (CDC) had estimates in 2013 to 2015 that the U.S. population aged 18 years or older as an estimated 22.7% (54.4 million) people with arthritis. That was projected to reach 67 million and 78 million Americans by 2025 and 2040, respectively. A large portion of that population needs to take medicine. So what are millions of Americans supposed to do when the U.S. Food & Drug Administration (FDA) issues enhanced warnings for some of the top arthritis drugs on the market?

The FDA is now going to require that new heart safety and cancer warnings

be included for Janus kinase inhibitors (JAK inhibitors) used to treat chronic inflammatory conditions. This includes the key drugs such as Xeljanz (Pfizer) after a postmarketing study, as well as Rinvoq (AbbVie) and Olumiant (Lilly). These JAK inhibitors already come with boxed warnings regarding increased risks of blood clots and lymphoma.

As a result of the warnings, the FDA is effectively pushing these drugs further down the line in the treatment sequence. The FDA is also now set to limit these JAK inhibitors in all approved indications, and they will be limited to certain patients who have either failed on treatments with TNF blockers or where they are not appropriate.

The postmarketing Xeljanz study was noted by the FDA:

This trial compared Xeljanz with another type of medicine used to treat arthritis called tumor necrosis factor (TNF) blockers in patients with rheumatoid arthritis. The trial’s final results also showed an increased risk of blood clots and death with the lower dose of Xeljanz. A prior DSC based upon earlier results from this trial, reported an increased risk of blood clots and death only seen at the higher dose.

While this postmarketing study pertained to Xeljanz, the new and updated warnings also includes the JAK inhibitors Olumiant (baricitinib) and Rinvoq (upadacitinib). It turns out that these JAK inhibitors are being lumped in with Xeljanz despite those drugs not being studied. The FDA communication said:

Olumiant and Rinvoq have not been studied in trials similar to the large safety clinical trial with Xeljanz, so the risks have not been adequately evaluated. However, since they share mechanisms of action withXeljanz, FDA considers that these medicines may have similar risks as seen in the Xeljanz safety trial.

The FDA further noted that two additional JAK inhibitors are not indicated for the treatment of arthritis and other inflammatory conditions. These are Jakafi (ruxolitinib) and Inrebic (fedratinib), and the FDA specified that these two drugs are not a part of the updates being required to the same prescribing information for Xeljanz, Xeljanz XR, Olumiant, and Rinvoq. Jakafi and Inrebic are used to treat blood disorders, and they require different updates to their prescribing information.

Effectively, the FDA is telling patients who are current (or past) smokers, who have had a heart attacks or other heart problems, or who have suffered a stroke or experienced blood clots in the past that the JAK inhibitors may put you at higher risk for serious problems.

The FDA specified in this postmarketing study that patients who were in the trial were all at least 50 years old and who also had at least one risk factor for heart disease.

The FDA did issue specific data in a summary. It said: “When FDA first approved Xeljanz (tofacitinib), we required the manufacturer, Pfizer, to conduct a randomized safety clinical trial in patients with rheumatoid arthritis (RA) who were taking methotrexate to evaluate the risk of cardiovascular events, malignancy, and infections. It was a multicenter, randomized, open-label trial to evaluate two doses of Xeljanz (5 mg twice daily (N=1455), which is the approved dosage for RA, and a higher 10 mg twice daily dosage (N=1456)) in comparison to treatment with a tumor necrosis factor (TNF) blocker (N=1451). Patients in the trial were required to be 50 years of age or older and have at least one cardiovascular risk factor. The co-primary endpoints were major adverse cardiovascular events (MACE), defined as cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke; and malignancy, excluding nonmelanoma skin cancer (NMSC). The trial was designed to exclude a prespecified risk margin of 1.8 for the hazard ratio of combined Xeljanz regimens when compared to the TNF blocker control for each co-primary endpoint. The median on-study follow-up time was 4 years.

“The mean age of the population was 61 years and the median age was 60 (range 50-88 years). Most patients were female (78 percent) and Caucasian (77 percent). The noninferiority criterion was not met for the comparison of the combined Xeljanz regimens to TNF blockers for the endpoints of MACE and malignancies since the upper limit of the 95% confidence intervals (CI) for these hazard ratios exceeded the prespecified noninferiority criterion of 1.8. For MACE, the estimated hazard ratio and 95% CI associated with the combined Xeljanz regimens relative to TNF blockers were 1.33 (0.91, 1.94). For malignancies excluding NMSC, the estimated hazard ratio and 95% CI associated with the combined Xeljanz regimens relative to TNF blockers were 1.48 (1.04, 2.09).

“There was an increased risk of death, MACE, malignancies, and thrombosis associated with both regimens of Xeljanz. The data showed evidence of a dose-dependent increased risk for MACE, all-cause mortality, and thrombosis at both doses of Xeljanz when compared to treatment with TNF blockers. Additionally, the data showed evidence of a non-dose-dependent increased risk for malignancy excluding NMSC at both doses of Xeljanz when compared to TNF blockers. Lymphomas and lung cancers were observed at a higher rate in patients treated at both doses of Xeljanz compared to those treated with TNF blockers. In particular, a higher rate of lung cancers was observed in current or past smokers treated with Xeljanz. Current or past smokers had an additional increased risk of overall cancers.

“Other JAK inhibitors have not been studied in similar large safety clinical trials, so the risk with these medicines has not been evaluated. However, since they share mechanisms of action with Xeljanz, FDA considers that these medicines may have similar risks as seen in the safety clinical trial with Xeljanz.”

The long and short of the matter is that many people will continue their current prescriptions while many other patients will need to stop taking these drugs and/or switch to other medicines. Some of those medicines are already known to not work as well, but they come with lower incidents of side effects.

This is not the first time that arthritis drugs have come under fire due to adverse instances of higher side effects.

About The Author

Kendra Evans

Kendra Evans founded Inflammation Guide in April 2020. Our goal is keeping our readers informed to help them live an empowered and full life while they manage inflammation. Inflammation Guide provides a central location for breaking news and updates on prescriptions, treatments, supplements and alternative wellness solutions to give options to people living with at least one inflammatory condition.

inflammation guide logo

You have Successfully Subscribed!