Tofacitinib and upadacitinib: rheumatoid arthritis pills instead of injections
When methotrexate could not control rheumatoid arthritis, there used to be one real option left: biologics. That means injections or infusions, often at a clinic. JAK inhibitors were the first serious arthritis drugs to come as ordinary tablets you take at home.
In the Unifarm catalogue these are Tofajak and Tofaxen (tofacitinib; the original is Xeljanz by Pfizer), and Upajak, LuciUpa and Rematib (upadacitinib; the original is Rinvoq by AbbVie). Below: how they work, how the two differ, and why doctors prescribe them with care.
What happens in the joint, and where JAK comes in
In rheumatoid arthritis the immune system makes a mistake: it treats the lining of your own joints as an enemy and keeps it inflamed for years. That is where the pain and morning stiffness come from, and over time the cartilage and bone get damaged.
Immune cells pass the “get inflamed” order to each other with signalling proteins. For a cell to act on it, the signal has to travel inside, and the enzymes that carry it are Janus kinases, or JAK. JAK inhibitors block that route inside the cell: the signal arrives but never reaches the nucleus. Biologics such as TNF inhibitors work differently, catching the signalling protein outside the cell. Same goal, different point of attack.
Tofacitinib and upadacitinib: what is the difference
First generation
blocks JAK1 and JAK3, twice a day
Second generation
aims more precisely at JAK1, once a day
| Parameter | Tofacitinib (Xeljanz) | Upadacitinib (Rinvoq) |
|---|---|---|
| Dosing | Twice a day | Once a day |
| Indications | Rheumatoid arthritis, psoriatic arthritis, ulcerative colitis | Rheumatoid arthritis, atopic dermatitis and others |
| In the Unifarm catalogue | Tofajak, Tofaxen | Upajak, LuciUpa, Rematib |
When JAK inhibitors are prescribed, and when they are not
Treatment does not start with them. The first step is almost always methotrexate or another conventional drug, and it is given a few months to work. If the inflammation stays, the rheumatologist moves to the next step: a biologic or a JAK inhibitor, often together with the same methotrexate at a lower dose.
Which one to choose depends on the person: age, heart and blood vessel health, past illnesses, earlier treatment. Sometimes daily life decides too. For some people a tablet is simply easier than self-injecting or travelling for infusions.
The risks, stated plainly
In 2021 the results of a large tofacitinib safety study (ORAL Surveillance) came in. Patients over 50 with heart risk factors had more heart attacks and strokes, blood clots and cancers on tofacitinib than on TNF inhibitors, and overall mortality was higher too. The FDA and EMA then added a warning to the whole class, upadacitinib included, although there is less data of this kind on upadacitinib itself.
What this means in practice:
- Before the first tablet the doctor assesses your heart, blood vessels and cancer history. Especially carefully in people over 50 and in smokers: the strictest warning applies to them.
- Infections are more common. The drug turns down part of the immune system, so the risk of shingles and serious infections goes up.
- Blood tests are regular. Full blood count, cholesterol, liver values: not once before starting, but for as long as treatment lasts.
- These are prescription drugs. Starting them, changing the dose or stopping on your own is not safe. That is the rheumatologist’s call.
This article is meant to make the conversation with your doctor easier, not to replace it.
