Do JAK inhibitor arthritis medicines raise cancer risk?

FDA's warning for these medicines includes symptoms that need urgent attention. They are not cancer symptoms. They are the heart, stroke and clotting risks named in the same communication.

• Call 911 or go to an emergency department if you have chest discomfort or tightness, sudden shortness of breath, weakness or numbness on one side of the body, slurred speech, or a leg or arm that becomes swollen, painful or discoloured. FDA says patients on these medicines should seek emergency help right away for any symptoms that may signal a heart attack, stroke or blood clot.
• Call your care team within a day or two if you notice a swollen gland that will not settle, drenching night sweats, unexplained weight loss, or a cough that keeps going. FDA links these medicines with an increased risk of certain cancers including lymphoma and lung cancer, and those are the changes worth having looked at.

Do not stop these medicines on your own because of what you read here. FDA's advice is to talk to your health care professional about any questions or concerns.

In September 2021 the FDA required new warnings on three medicines. They belong to a class called JAK inhibitors. They are Xeljanz and Xeljanz XR (tofacitinib), Olumiant (baricitinib) and Rinvoq (upadacitinib). All three are approved for rheumatoid arthritis. Xeljanz is also approved for psoriatic arthritis, ulcerative colitis and polyarticular course juvenile idiopathic arthritis.

A large randomised safety trial set this off. It compared Xeljanz against TNF blockers in people with rheumatoid arthritis. TNF blockers are an older, well-established class of drug for the same conditions. FDA concluded from that review that there is an increased risk of serious heart-related events such as heart attack or stroke, cancer, blood clots and death with Xeljanz and Xeljanz XR.

Olumiant and Rinvoq were not studied in a trial like that one, so their risks have not been adequately evaluated. FDA extended the warnings anyway, because these medicines share a mechanism of action with Xeljanz and may carry similar risks.

FDA's wording on cancer is broad rather than itemised. Treatment with these medicines is associated with an increased risk of certain cancers including lymphoma and lung cancer. Lymphomas are cancers that begin in white blood cells.

Smoking comes into it as a risk factor rather than as a separate finding. FDA asks patients to say whether they are a current or past smoker, and tells prescribers to be especially careful in that group, as well as in people with other cardiovascular risk factors, people who develop a malignancy, and people with a known malignancy other than a successfully treated nonmelanoma skin cancer.

Inflammation is a signalling problem as much as a chemical one. Janus kinase enzymes sit inside cells. They pass along inflammation messages that arrive from outside. Blocking them turns down a lot of those messages at once.

That broad reach is what makes these drugs work when other treatments have not. It is also why a safety review of this kind was worth doing.

The agency's guidance to prescribers is specific. Reserve these medicines for patients who have had an inadequate response to one or more TNF blockers, or who cannot tolerate them. In short, they are a later option rather than a first move.

For patients, FDA asks two things before you start. Tell your health care professional about your smoking history. And tell them about any past heart attack, other heart problems, stroke or blood clots.

A warning label describes a trade-off. It is not a verdict on whether a medicine is worth taking.

Untreated inflammatory arthritis is not a neutral alternative. It damages joints. It limits what people can do. Over years, it carries its own costs. That side of the ledger belongs in the conversation too.

What changed in 2021 is that the trade-off is now spelled out on the label. Prescribers are expected to weigh it carefully for each person. Say you take one of these three medicines. The useful step is a conversation at your next appointment. Cover what you have already tried, whether you have smoked, what your heart history looks like, and whether this is still the right choice for you.