The JAK inhibitors in Rheumatoid Arthritis

There are now many treatments available for Rheumatoid Arthritis (see our overview).

The JAK inhibitors – tofacitinib and baricitinib – have the major advantage of being tablets rather

than injections. They have been tested quite extensively in rheumatoid arthritis and are being

explored for other rheumatic conditions. So, what do we think of them so far? This is the state of

play as of March 2020.


Do JAK inhibitors work?


They have been trialled in a series of trials in patients who have had active disease despite

methotrexate, and sometimes other drugs too. 1 in 4 patients had a very good response (ACR70)

compared to 1 in 8 with methotrexate.

Do JAK Inhibitors Work?

Tofacitinib was trialled as a first drug in rheumatoid arthritis in comparison to Methotrexate. Overall about 45% of patients on tofacitinib had at least a 20% improvement in their rheumatoid arthritis (called the ‘ACR20’ response).


Baricitinib was tested in patients who had active disease despite methotrexate. 70% had at least

20% improvement, compared to 60% with injections of adalimumab (an anti-TNF biologic therapy)

and 40% with neither. And 37% of patients achieved a good response (70% improvement) compared

to 31% with adalimumab. These differences were not significantly different after a year.


What are the side effects?


Infections - Infections are common overall (between 1:10 and 1:100) including shingles, pneumonia

and urinary tract infections. The rate of serious infections seems no different to placebo in baricitinib. Tofacitinib is associated with serious infections of many different types, most commonly shingles and pneumonia. Overall shingles occurs in about 3.5% of patients each year and serious infections in 2.5% each year.


Blood levels - Changes in blood levels of creatinine (an indicator of kidney function), white cells,

haemoglobin and cholesterol are common. But they are usually mild and don’t require stopping the

drug.


Blood clots - There is a concern about increased risk of blood clots with both medications.


Cancer - The association with cancer – an increase in cancers has been seen with tofacitinib but not

reported with baricitinib.


The European guidelines 2019 update recommend methotrexate as the first line, additional conventional synthetic DMARDs as the second line, and then either JAK inhibitors or biologic DMARDs. They felt there was “new evidence regarding the successful long-term efficacy and safety

of JAK inhibitors”.


However – hot off the press. On 7 th February 2020 the manufacturers of Tofacitinib issued a

warning about increased risk of death, which was 2-3 times as high in tofacitinib as in patients

treated with anti-TNF inhibitor in an ongoing study. Deaths were due to cardiovascular events (heart

attacks and strokes), infections and cancers.


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