Supplementary IM steroids in RA: Toxicity outweighs benefit?

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Supplementary IM steroids in RA: Toxicity outweighs benefit?



Aug 23, 2005



Birmingham

London, UK - Patients with established rheumatoid arthritis (RA)

inadequately controlled by disease-modifying antirheumatic drugs

(DMARDs) should not be given supplementary steroids except in the

very short term because of steroid-associated side effects, according

to Prof and colleagues (GKT School of Medicine, Kings

College, London, UK). " We've always used [intramuscular] depot

methylprednisolone short term in people having a flare . . . but in

the long term I feel that it's not going to be the way forward, and

we need to be giving either more DMARDS in combination therapy or

biological agents with DMARDs, " tells rheumawire.

The conclusion comes from a two-year prospective randomized

controlled trial, published in the September 2005 ls of the

Rheumatic Diseases [1]. 's team examined the value of monthly

intramuscular (IM) injections of 120-mg depomedrone (depot

methylprednisolone acetate) (n=48) vs saline placebo (n=43) in

patients with established active rheumatoid arthritis already

receiving DMARDs. Patients continued DMARD use at the same dose, and

one of the allowed DMARDs (gold, penicillamine, methotrexate,

azathioprine, or cyclosporin) could be changed for another under

supervision. Disease activity and side effects were assessed every

six months, and radiological damage in the hands and feet every 12

months.

Disease activity improved rapidly in the steroid group, with swollen

joint counts, pain, Health Assessment Questionnaire (HAQ), and

disease activity scores (DAS) all being reduced. However, this

difference between the two groups disappeared after six months. X-ray

(Larsen) scores deteriorated significantly in the placebo group over

the 24-month test period but not the steroid group. Despite these

small protective effects, more adverse events were reported in the

steroid than the placebo group (55 vs 42 reports), particularly in

terms of side effects traditionally associated with steroids (16 vs 2

reports, p=0.0008). In the group receiving IM depomedrone, these

included: hypertension requiring treatment (4 patients), facial

swelling (3), bruising (3), osteoporosis (2, including one vertebral

fracture), diabetes mellitus (1), myocardial infarction (1),

hypercholesterolemia (1), and iatrogenic 's disease (1). By

contrast, only two patients in the placebo group had any such side

effects (one case of hypertension, one of weight gain).

" We found that in the short term DAS score improves but not as much

as with TNF inhibitors. We also found fairly clear-cut evidence that

x-ray progression is reduced in the long term, but we were quite

surprised with how many side effects there were, " comments. The

steroid used in this trial, a standard dose of 120-mg IM

methylprednisolone monthly, is roughly equivalent to 6.5-mg/day oral

prednisone for most of the month, although plasma levels decrease

gradually to become undetectable by three weeks. " Our hope at the

time was that this would be pretty safe because 6.5 mg is a low-dose

schedule, and we didn't think there would be much toxicity, because

we often use it in the clinic. The study was conceived before anti-

TNF was used as it is now, and we thought it would be a cheap and

cheerful alternative to giving people anti-TNF; in terms of cost/

benefit it should be off the scale. But in terms of the overall

situation, we thought the toxicity outweighed the benefits. The

result was not one that leads me to want to go on using it, so it's

changed clinical practice in a negative way. "



One sobering finding of the study was that glucocorticoid treatment

induced osteoporosis. Bone density fell by 15% to 18% over the two

years in the depomedrone group, whereas there was little or no change

in the placebo group. The patients were not treated with bone-

protective agents, as this was not standard practice at the time, the

researchers comment. However, 's group advocates that

osteoprotective therapy should now be given if this steroid regimen

is used in patients.

" The concept that steroids can reduce x-ray progression is probably

true at all times in the disease, " says , " but I'm not certain

it's a helpful thing to know because of the toxicitywe definitely

felt that osteoporosis is an issue. "

" For the future, DMARD therapies aren't great, and we need to move

beyond that. Certainly combinations are one approach, and with short-

term steroids in early RA this seems okay. But then it's the question

of DMARD combinations and/or anti-TNF and the question is always

going to be the cost/benefit of anti-TNF, which is a difficult one, "

he says.

In their paper, the researchers conclude: " IM steroid treatment

produces only a transient clinical benefit. Although it may have a

small protective effect against erosions, the level of steroid-

related adverse events precludes its use as a long-term treatment

strategy. "



Source 

Choy EH, Kingsley GH, Khoshaba B, et al. A two-year randomised

controlled trial of intramuscular depot steroids in patients with

established rheumatoid arthritis who have shown an incomplete

response to disease modifying antirheumatic drugs. Ann Rheum Dis

2005; 64; 1288-1293.



http://www.jointandbone.org/viewArticle.do?primaryKey=545879