Polymyalgia Rheumatica and Steroid Side Effects: New Findings

[Admiral06]

Except for cataracts, side effects in PMR patients treated with glucocorticoids and non-PMR patients were not statistically different, new research finds.

By Kathleen Doheny

Interviews with Eric L. Matteson, MD, MPH, and Don L. Goldenberg, MD

Glucocorticoids, primarily prednisone, are the standard treatment for those affected by polymyalgia rheumatica (PMR), a common inflammatory disease of older adults that causes joint pain. Unfortunately, steroid use is known to be associated with adverse effects, including a risk of developing diabetes, osteoporosis, fractures, high blood sugar, cataracts, and other problems.

New research suggests most of those adverse effects are no more common in PMR patients treated with glucocorticoids than in matched control patients without PMR who aren't treated with the drugs.1

"The event rates for the side effects that we often attribute to steroids were actually the same in the control group, except for cataract development," said Eric L. Matteson, MD, MPH, a consultant and professor of medicine at Mayo Clinic Rochester and senior author of the study.

He believes this is the first study to compare side effects in PMR patients treated with steroids and patients without a PMR diagnosis and not on steroids. Besides the finding on side effects, he added, the research shed light on factors such as average doses and length of treatment.1

Study Details

The American College of Rheumatology and European League Against Rheumatism issued joint recommendations in 2015, recommending the lowest starting dose and least duration to manage the condition. It recommends a start dose of 12.5 to 25 mg of prednisone equivalent daily, not to surpass 30 mg.2

Dr. Matteson and his team, all from Mayo Clinic, used a population-based inception cohort, obtaining details of the glucocorticoid therapy from the medical records of 359 patients diagnosed with PMR from 2000 through 2014. Next, they found 359 age- and sex-matched controls without PMR from the same population.

They looked at cumulative and daily doses of steroids, rate of disease relapses, the rate of discontinuation and side effects.1

In the new study, the median time to taper below 5 mg a day for 6 months was 1.44 years (95% CI, 1.36-1.62) and the median time to permanent discontinuation was 5.95 years (95% CI: 3.37-8.88). At 2 years, the mean cumulative dose was 4 g and at 5 years, 6.3 g. The mean daily dose at 2 years was 6.1 mg and 7.2 mg at 5 years. The average initial dose was 16.9 mg daily.

The researchers found no statistically significant differences in the rates of diabetes, hypertension, hyperlipidemia, or fractures of the hip, vertebrae or Colles fractures between PMR patients and controls. (P > 0.2 for all). However, those on steroids were more likely to develop cataracts (hazard ratio 1.72; 95% CI: 1.23-2.41).

Among the noteworthy findings:

A significant proportion of those with the condition were on low-dose steroids for many years.

Those on lengthy treatment do experience a high rate of steroid-related complications, but except for cataracts, these comorbidities are no more common in PMR patients than in non-PMR patients.1

Expert Perspective

Historically, physicians have worried about using higher doses of steroids for longer periods of time, said Don Goldenberg, MD, professor of medicine, emeritus at Tufts University School of Medicine and adjunct faculty, department of medicine and nursing, Oregon Health Sciences University, Portland. He is a member of the Practical Pain Management editorial board and reviewed the new findings.

The findings are mostly reassuring, he said, although those on steroids did have a higher incidence of cataracts The cumulative incidence of cataracts at 5 years after the PMR diagnosis was 41% for those diagnosed compared to 27.3% of those not diagnosed. He, too, pointed to the possibility that those with PMR may have had more eye exams, which the authors of the study also noted.

The initial mean starting dose (16.9 mg daily) and the duration of steroid use was a bit surprising, he said. The average among rheumatologists is about 10 or 15 mg, he said, "I personally seldom had patients on for 6 years.''

Even so, he believed that ''the good news outweighs the bad news here."

More Insights from Dr. Matteson

While the association guidelines do spell out an ideal dose range, they do not specify ideal length of treatment, noted Dr. Matteson, instead specifying the minimum effective duration.

In general, Dr. Matteson told Practical Pain Management, ''it's been thought 2 or 3 years'' might be enough. However, the median in the study was actually 6 years. The study also suggested relapses are common and most often occur in the first 2 or 3 years, he said.

Although the overall event rates were not different, except for cataracts, Dr. Matteson said, some individuals did have troublesome side effects.

The study excluded some, including those who already had diabetes. So the study did not look at whether the steroids led to a worsening of pre-existing conditions, he said. The study also excluded those with giant cell arteritis (GCA), which can occur with PMR.

The higher incidence of cataracts in the steroid-treated group may have been due to concerns about coexistent GCA, and that might have triggered eye exams and the discovery of cataracts soon after the diagnosis, the authors noted in the article.

While the findings are somewhat good news regarding side effects, steroids are often not popular among patients, Dr. Matteson noted, due to other concerns, such as the weight gain associated with steroid use. The researchers did not examine weight gain. Nor did they look at appearance changes due to the drug or mood changes, also problematic for patients.

Dr. Matteson emphasized that these findings do not mean that experts should not continue to look for a better treatment options.

[SheffieldJane]

Thank you so much for summarising these findings in a clear and helpful way. Although I was aware of this from a link to the study that PMR posted on a couple of occasions. It is useful ammunition when our doctors want us to get off steroids too quickly at all costs, which seems to happen to a lot of patients. It is reassuring for those of us who have to take them for prolonged periods and fear that we are storing up problems for later. It is true that we go for more thorough eye examinations, I certainly do.

[Marie1479]

I developed high blood sugar, high cholesterol, osteopenia, blurry vision, bruising etc the first year on steroids. Since on Actemra, and a strict diet I was able to significantly lower steroid dose, lowing high blood sugar and cholesterol and blurry vision is gone. I guess some are more sensitive to steroids than others.

I don’t believe PMR affects the joints. For me It caused inflammation of my tissue and muscles.

[GerriMc in reply to Marie1479]

Just going to say that, I never had a problem with my joints, the pain was in the large muscles (shoulder, glutes, etc).

[PMRpro Ambassador in reply to Marie1479]

No I don't think it affects joints in many people - although it DOES cause synovitis in some and I assume that is what they think it is. One day we'll get through to them

[CRW-68 in reply to Marie1479]

My Rheumatologist just suggested to me to consider Actemra. She wanted me to study it and at my next appointment we will discuss. The warnings are a bit frightening, but as always we need to weigh the risks of long term Prednisone usage.

Have you had any problems with infections? Does your insurance cover it. I am in the US with Medicare, Secondary insurance, and a Part D prescription plan. My understanding is that if it can be given at an infusion center Medicare will cover it. If you give it by yourself then it falls under the Part D prescription plan which will pay partial leaving my out of pocket abt. 1k + per month. I certainly can not afford that! I am not eligable for financial help.

Please tell me about your experience with Actemra.

Thank you.

[Marie1479 in reply to CRW-68]

The warning signs of prednisone are bad too. Actually most meds are. I feel like a new person and I’ve been able to reduce by more than half. I’m able to work full-time and have an almost normal life. I wrote a lot about my Actemra experience. click on my profile to view posts.

[PMRpro Ambassador in reply to CRW-68]

Look at the top right corner of the page where you sill see a box saying "Search PMRGCAuk". Type in Actemra and you will get a lsit of all the threads talking about it.

[CRW-68 in reply to PMRpro]

Thank you. I did, and was very helpful.

[EdithWales]

Thank you That’s very reassuring

[Ozark]

I have looked into this and according to a piece on Medpage Today this conclusion above by my reading is not correct and I quote from the article:

"A retrospective, observational, population-based study found no difference in rates of diabetes, hypertension, hyperlipidemia, or hip, vertebral or Colles fractures in PMR versus non-PMR patients on long-term steroid therapy, reported Eric Matteson, MD, MPH, and colleagues at the Mayo Clinic in Rochester, Minn."

This study did NOT apparently say that PMR patients would not see more side-effects from pred over time, only that when compared to non-PMR "steroid users" the same level of side-effects were apparent in both cases, just not higher with PMR patients, with the exception of cataracts. It did not exonerate pred over longer periods of time from the increased possibility of serious side effects. Many reprints of this study fail to mention the the non-PMR patients were "also" on steroids, not just members of the general population, which is misleading. At least this is my reading of the study.

The whole article is here, though you may have to sign-up for free to read it:

medpagetoday.com/rheumatolo...

[clieder in reply to Ozark]

That's a major "oops." I clearly understood it to say that the comparison was to non-PMR, non-steroid users. So, the only remaining thing of interest is the length of illness and average treatment dose, also interesting, but not as profound as the former would have been. Thanks for clarifying.