RESEARCH - Supplementary IM steroids in RA: Toxicity outweighs benefit?

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Supplementary IM steroids in RA: Toxicity outweighs benefit?

Rheumawire

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 toxicity - we 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

1. 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.

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