12 February 2018

Methotrexate overlooked for treating PMR

Clinical Drugs Rheumatology

Experts are urging doctors to consider methotrexate for patients with polymyalgia rheumatica (PMR), instead of continuing to increase corticosteroid doses.

While prednisolone was recommended as the most effective first-line treatment for PMR, prolonged use of corticosteroids had a host of potentially harmful effects, rheumatologist and clinical pharmacologist Dr David Liew warned.

“Polymyalgia rheumatica is one of the few conditions … where there is a paradigm that we are happy to tolerate long-term prednisolone,” he told The Medical Republic. “And that really comes with a whole burden of morbidity that is underappreciated.”

While clinicians typically thought of morbidity resulting from high dose prednisolone, it was certainly an issue for these patients who might have to take lower doses of the steroid for as long as five years, he said.

To combat this confusion around the long-term management, Dr David Liew and colleagues wrote a guide to prescribing in Australian Prescriber.

Prednisolone is still the first line treatment for PMR, with guidelines recommending an initial dose of 15mg for three weeks, although some patients may require 25mg to alleviate symptoms.

And while tapering regimens can vary greatly, most schedules involve at least 46 weeks of prednisolone therapy.

“We try to use the least effective dose and try and bring it down as quickly as possible,” Dr Liew said. “But at the same time, we know too rapid a de-escalation can actually be going one step forward and two steps back and can actually lead to greater steroid exposure for patients.”

It was important to personalise treatment and clinicians could consider methotrexate in patients who continued to experience flare-ups, as defined by a recurrence of symptoms and a rise in inflammatory markers during the weaning process, Dr Liew said.

These were the patients who couldn’t seem to get below a certain dose during the tapering process, whether it was 5mg or 10mg per day, he added.

Dr Liew said that while there was a lack of good evidence for methotrexate, it did appear to work in some patients and was recommended in European guidelines.

And using a steroid-sparing agent was particularly worthwhile considering because, for reasons that were still unclear, the morbidity from similar doses of corticosteroids was more severe and occurred more frequently in PMR than in other rheumatic diseases, Dr Liew explained.

“The cumulative effect, however, is that up to 81% of patients develop adverse events in the first year,” Dr Liew and his colleagues wrote.

“Furthermore, polymyalgia rheumatica is a disease of older people, who are at risk of complications as a consequence of these adverse events.

“Uncontrolled inflammation itself can also cause problems, therefore corticosteroid therapy in polymyalgia rheumatica is a balance. Aim to achieve the minimum total exposure to prednisolone while maintaining control of the disease.”

Dr Liew warned that methotrexate was not an ideal alternative and hoped for the development of a better steroid-sparing drug.

“Methotrexate can be dangerous drug if the right safety elements aren’t put into place,” he said. Dr Liew also urged doctors to be alert for giant cell arteritis, which was associated with PMR.