VIDEO: 'Exciting time' for therapeutic options in polymyalgia rheumatica

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So this is certainly an exciting time to talk about therapeutic options for PMR because until very, very recently we haven't had much besides glucocorticoids to really ramble on. Glucocorticoids, and then the use, of course, prednisone or methylprednisolone in some patients remain still the first line of treatment for patients with PMR. This has been the case and is outlined by the 2015 ACR/EULAR recommendations. They recommended a starting dose between 12.5 to 25. Usually if you were asked, majority of rheumatologists would consider doses between 15 and 20 as a starting dose for patients with PMR. And we know that usually that provides a relief for the vast majority of patients with PMR. Again, a lack of response always needs to not necessarily kind of put a little bit of alert. And that's one of the challenges of course with PMR as I mentioned in the previous question, is that there can sometimes be a little bit of uncertainty in the diagnosis. So that's always something to be monitoring if there's a lack of response, if there are other features. But usually those doses would allow and provide adequate treatment for patients with PMR.

However, as we know, trajectories in treatment with the use of glucocorticoids and the requirement of glucocorticoids for patients with PMR can be very variable. There is not a gold standard for specific taper as much as there is an outline for a taper recommendation by the 2015 ACR/EULAR recommendations, and again, variability. Some physicians tend to challenge patients with faster tapers, although there's always the caveat on that, that those faster tapers have been associated with a higher risk of not only relapse but also longer duration of glucocorticoid use. But vast majority of patients actually remain on glucocorticoids, from most of the studies published to date, up to two years. So in one recent analysis that we did using the ACR RISE registry, almost 2/3 of patients who were, these again are patients, RISE's rheumatology provider registry. So these are patients under rheumatology care, but almost 2/3 of patients remained on glucocorticoids at two years. As I said, there's patients who remain on it even up to five years and there's systematic review and meta-analysis that showed up to 25% of patients remain on glucocorticoids up to five years. There's a large spectrum on the need and the duration of glucocorticoid treatment, and we still have a pretty big unmet need of better identifying who are those patients who will require prolonged glucocorticoid treatment.

Until recently as well, with regards to kind of what the recommendations were, although there were some limitations with regards to the clinical trials done on the use of methotrexate as a steroid sparing agent for PMR, methotrexate has usually been the agent of choice. And there were a few clinical trials that actually showed some benefit. And of course in late 2023, we saw the approval of sarilumab, which is an interleukin-six inhibitor for the treatment of relapsing or refractory PMR. And it's an exciting time given that we already knew about the positive experience in the treatment of IL-6 inhibitors for GCA and GCA with PMR. There were of course some epidemiological studies and some smaller trials, but the phase III trial on sarilumab (Kevzara, Sanofi) showed efficacy for this specific population, again refractory and relapsing disease, and is now approved for its use in these patients.

Other options, probably currently under study or particularly with some of the conventional immunomodulatory agents such as leflunomide (Arava, Sanofi), this probably has some more uptake in the UK, but there's actually now a study going on, a randomized control trial regarding the use of leflunomide that is happening in Europe and Australasia. There's always been some use, and we've seen this as well in some of our real-world data regarding hydroxychloroquine use, azathioprine, sulfasalazine, not that I can say that there's much data necessarily to back that up. But I think it's again, extrapolated from the use of other inflammatory arthritis. Plus the fact as I said at the beginning of this question is we didn't have much. So I think we wanted to offer options to our patients and also minimize glucocorticoids, which remains a big issue and unmet need in these patients. Another kind of biologic agents or targeted synthetic DMARDs that are under study include, well, the IL-17 inhibitors as well are now being studied. There's one small trial with rituximab (Rituxan, Genentech) as well, which still, I don't know if there's any plans for phase III, and there are trials going on with JAK inhibitors as well for the treatment of PMR.