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PMR News from Med page 1.10.23

JanetGarrettN profile image
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Rheumatology > General Rheumatology

JAK Inhibitor Promising for Polymyalgia Rheumatica

— Oral drug seen as safer than chronic, high-dose steroids

by John Gever, Contributing Writer, MedPage Today

January 9, 2023

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A photo of a senior woman grimacing and grasping her shoulders next to a bottle of Xeljanz

Tofacitinib (Xeljanz) appeared highly effective against polymyalgia rheumatica (PMR) in a small single-arm trial, researchers said, suggesting another potential alternative to long-term corticosteroids.

Among 14 patients in a phase II studyopens in a new tab or window treated with the oral Janus-associated kinase (JAK) inhibitor, mean disease activity ratings on a standard scale fell from 50.9 points at baseline to just 1.3 after 48 weeks, according to Ting Li, PhD, of Shanghai Jiao Tong University School of Medicine in China, and colleagues.

Perhaps just as important, this improvement was achieved with a steep reduction in steroid doses, the researchers reported in the Annals of the Rheumatic Diseasesopens in a new tab or window: from 15 mg/day of prednisone at baseline to a mean of 1.9 mg/day at week 48.

These findings, along with recent studies with a different targeted agent, point to a coming sea change for PMR treatment.

Steroids are now the "mainstay" of therapy for PMR, Li and colleagues observed. "For conventional synthetic disease-modifying anti-rheumatic drugs [DMARDs, such as methotrexate], there is no convincing evidence of efficacy," they wrote.

In 2022, however, results of two significant trials with tocilizumab (Actemra) were published, both indicating substantial efficacy. But one came with important caveats,opens in a new tab or window including less-than-comprehensive safety results, while the otheropens in a new tab or window, said Li and colleagues, had issues with the outcome assessments. Tocilizumab is also an injectable product and some patients may need or prefer oral dosing. JAK inhibitors have shown generally equivalent effectiveness with biologic drugs for many other rheumatologic conditions, making tofacitinib a logical choice for testing.

The 14 patients all were diagnosed with highly active PMR, defined as a score higher than 17 on the PMR Activity Scaleopens in a new tab or window. Three of the patients had previously tried conventional DMARDs and relapsed, while the rest were newly diagnosed. Their mean age was 69, and just under three-quarters were women.

Tofacitinib was given at 10 mg/day along with, to start, 15 mg/day of prednisone. The latter was then tapered over 20 weeks to 2.5 mg/day or less. Other agents including over-the-counter anti-inflammatory drugs were forbidden.

Achievement of PMR activity scores less than 7, defined as remission, was the primary outcome measure. By week 20, all but two of the 14 had achieved it, the researchers reported, with the remaining two getting there by week 48

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JanetGarrettN
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DorsetLady profile image
DorsetLadyPMRGCAuk volunteer

link here -

medpagetoday.com/rheumatolo...

PMRpro profile image
PMRproAmbassador

It's a bit SMALL!!! Leflunomide was used in a study years ago with it claimed that 21 out of 23 patients got off pred. If you've been following recent posts you'll know it doesn't appear to have similar success in real life! If the JAK-inhibitors parallel MTX and LEF in real life though they will work for a small group of PMR patients.

However - since they have similar costs to the MABs (IRO £1000 per month), the cynic in me says NICE won't like them ...

JanetGarrettN profile image
JanetGarrettN in reply toPMRpro

Any progress is good. I'm in US. After 4 yrs 3 mo. am down to 2 mg Prednisone. So ready to say goodbye.

PMRpro profile image
PMRproAmbassador in reply toJanetGarrettN

Shhhhhh!!!! It might hear and chuck a spanner in the works ;)

DeepThought2 profile image
DeepThought2 in reply toPMRpro

I fully agree - much more proof is needed. It is still interesting though, as JAK inhibitors target a central hub for inflammatory signals. They also come with risks and at least in Germany they should be used in e.g., RA only if other DMARDs (including biologicals) do not work.

PMRpro profile image
PMRproAmbassador in reply toDeepThought2

It will be interesting to see if anyone takes them up for larger studies. No-one ever did with leflunomide and methotrexate is used a lot without any real proof as yet of efficacy. A study is finally supposed to be under way.

DeepThought2 profile image
DeepThought2 in reply toPMRpro

maybe (or most likely) a matter of money - as the JAKinibs are much more expensive than e.g., MTX there might be more incentives for industry to sponsor larger trails.

PMRpro profile image
PMRproAmbassador in reply toDeepThought2

Maybe - but I doubt the health systems can really afford them

Heron82 profile image
Heron82

Is this Pfizer trying to find a new indication for this drug?

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