Wednesday, 21 Aug 2019

You are here

A New Era? JAK inhibitors in the Management of RA

ACR 2018 has come and gone. It was a conference filled with a number of highlights. One thing from this conference which really stood out was the continued plethora of data on JAK inhibitors. First in RA, and now in psoriatic arthritis and psoriasis.

There was a time when the gold standard of a new biologic in RA was hitting an ACR 20/50/70 of 60%, 40% and 20% respectively in a MTX IR population. In the new era of JAK inhibitors, the expectations are now higher, where we often see ACR scores of 70/50/30 in the for the ACR 20/50/70 scores respectively in the same population.

At this conference, the presentation of data for upadacitinib and filgotinib, both JAK-1 selective inhibitors, have continued push the case for the widespread use of these agents. For example, the SELECT COMPARE study, assessing the efficacy of upadacitinib 15mg OD versus Humira 40mg EOW or placebo showed that upadacitinib was similar to Humira in most efficacy domains, but in most cases were numerically superior, in addition to being statistically significant in achieving the all important ACR 50 response. This adds the the growing number of studies which show that JAKs are at least non-inferior to a TNF inhibitor, but may in fact be considered superior, depending on how much you scrutinize the methadological basis of such a claim.

Another thing that I find striking as I reviewed multiple posters about JAK inhibitors is how quickly they seem to work. In both the upacitinib and filgotinib phase 3 trials, most patients notice a significant improvement in pain, and quality of life by even 1 week. This is similar to previous data presented on tofacitinib and baricitinib. Therefore, I expect JAK inhibitors as a class in general to work very quickly.

Although we still define a primary failure to a biologic as a lack of optimal response by 6 months of initiating, I would argue that this rule does not apply to the JAK family. Those who will respond will likely respond early, and we are likely doing patients a disservice by waiting until the 6 months to switch inadequate responders. Perhaps for this class, even 3 months may be sufficient to be considered a primary failure to a JAK inhibitor? This is something that I will be incorporating into my own clinical practice and will try to assess my JAK patients sooner rather than later, after initiating treatment, and switching out earlier if needed.

I still remain part of the old guard, who still use a TNF inhibitor as first line after failing DMARDs. This stems more from old habits and greater comfort level from past experience that anything else. However, as an rheumatologist/epidemiologist who tries to incorporate best evidence into practice, it is becoming increasingly tough to justify these old habits. I still think the TNFs are a great class of molecules and don’t plan on abandoning them, but I think it may be time to share the spotlight here.

Add new comment

More Like This

Good Pregnancy Outcomes for DMARD Exposed JIA Patients

A study of pregnancy outcomes in 98 women with juvenile idiopathic arthritis (JIA) who were exposed to DMARDs shows no increased risk of major adverse pregnancy outcomes.

A total of 152 pregnancies in 98 women with JIA and 39 pregnancies involving 21 male patients as partners were reviewed. The majority had a polyarticular JIA (61%). The average age at first pregnancy was 24.1 years, and their mean disease duration was 13.8 years.

Autoantibodies Don't Disappear With Remission in RA

Immunologic remission in rheumatoid arthritis, defined as the disappearance of anti-citrullinated protein antibodies and rheumatoid factor, was seen infrequently among patients achieving sustained clinical remission and did not correlate with the disappearance of symptoms, a long-term Dutch study found.

Updated CDC Recommendation for Serologic Diagnosis of Lyme Disease

Serologic testing is the principal means of laboratory diagnosis of Lyme disease. Current recommendations include using a sensitive enzyme immunoassay (EIA) or immunofluorescence assay, followed by a western immunoblot assay for specimens yielding positive or equivocal results. On July 29, 2019, the Food and Drug Administration cleared several Lyme disease serologic assays with new indications for use, allowing for an EIA rather than western immunoblot assay as the second test in a Lyme disease testing algorithm. Thus, serologic assays that utilize a second EIA in place of western immunoblot assay are acceptable alternatives for the serologic diagnosis of Lyme disease.

Trends in Inflammatory Arthritis Care in Germany

The German National Database (NDB) has reviewed their experience in the care and quality of life of inflammatory rheumatic disease patients snce 1993, showing improved use of metrics, improved outcomes and a changing profile of biologic and anti-rheumatic drug use.  

War on RA – Part 4: Desperado – Time to Open the Gate

Do you know what the best-selling album of all time is? Could it be Bing Crosby? U2? Fleetwood Mac? AC/DC? I know, it’s Michael Jackson’s “Thriller” right? Actually it’s the Eagles Greatest Hits – it surpassed Jackson’s Thriller in August 2019 as the best-selling with a total of 36 million copies sold since it was released in 1976. Wait! Are we not Rheumatologists? Aren’t we supposed to be discussing rheumatoid arthritis?