INFO - What is low-dose/high-dose prednisone in the treatment of RA?

[Guest guest]

" First, what is meant by " low-dose " prednisone? A

dosage of 10 mg/d may be regarded as " intermediate " or

even " high " by some clinicians, including ourselves. In

146 of 152 patients with rheumatoid arthritis who took

corticosteroids over 1 to 20 years (median, 6.7 years)

under care of the first author of this editorial between

1998 and 2001, the median prednisone dose was 4 mg,

in 1-mg tablets. Only 10% of patients were taking more

than 8 mg/d, which is regarded as a " high " dose in our

clinic. The current initial prednisone dosage in most

patients is 3 mg/d. The prevalence of hypertension, cataracts,

or diabetes in these patients did not differ from

that seen in a cohort of patients with early rheumatoid

arthritis (Sokka T, Pincus T. In preparation). However,

thinning and bruising of the skin are common, and

questions of skeletal maintenance remain unresolved because

formal bone density studies are not yet available in

all patients. "

Source:

76 1 January 2002 ls of Internal Medicine Volume 136 . Number 1

" Are Long-Term Very Low Doses of Prednisone for Patients with Rheumatoid

Arthritis as Helpful as High Doses are Harmful? " :

http://www.annals.org/cgi/content/full/136/1/76

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" Glucocorticoids. Low-dose oral glucocorticoids

(< 10 mg of prednisone daily, or the equivalent) and

local injections of glucocorticoids are highly effective for

relieving symptoms in patients with active RA. A patient

disabled by active polyarthritis may experience marked

and rapid improvement in functional status within a

matter of days following initiation of low-dose glucocorticoids.

Frequently, disabling synovitis recurs when glucocorticoids

are discontinued, even in patients who are

receiving combination therapy with one or more

DMARDs. Therefore, many patients with RA are functionally

dependent on glucocorticoids and continue

them long-term. "

Source:

American College of Rheumatology

" 2002 Guidelines for the Management of Rheumatoid Arthritis " :

http://www.rheumatology.org/publications/guidelines/raguidelines02.asp?aud=mem

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" The treatment of early rheumatoid

arthritis (RA) remains controversial.

Use of TNF alpha blockade in patients

with relatively severe early disease

does not lead to substantially improved

responses compared with methotrexate

alone (1,2). The benefit to risk ratio of

all disease modifying antirheumatic

agents (DMARDs) requires their judicious

use, tailored to the individual

patient.

Use of glucocorticoids in early RA has

remained controversial. Although well

recognized to offer symptomatic

improvement, and short term benefit on

radiographic disease progression,

glucocorticoids are still not regarded as

DMARDs. Potentially severe adverse

effects associated with chronic

administration including weight gain,

diabetes, hypertension, cataracts, and

osteoporotic fractures have led many to

recommend their use in long-term

treatment of RA be restricted to

patients with early disease.

Unfortunately, limited data are available to

assess the benefit / risk profile of low

dose (prednisone < 7.5 mg daily or

equivalent) glucocorticoid therapy in

early rheumatoid arthritis, within 2

years of diagnosis. We summarize here

the evidence for and against use of low

dose glucocorticoids in patients with

early RA, and preventive measures for

glucocorticoid-induced osteoporosis. "

Source:

Clinical and Experimental Rheumatology 2003

" Low dose glucocorticoids in early rheumatoid arthritis " :

http://www.clinexprheumatol.org/pdf/vol21/s31/s31_pdf/33strand.pdf

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" Eschewing the use of high dose regimens,

the goal is symptomatic improvement

and potential disease modification

with the lowest possible effective

dose (16). Once improvement is achieved,

tapering to a more physiologic dosage

(less than 7.5 mg/d) should be

strongly considered in most patients. "

Source:

Clinical and Experimental Rheumatology 2004

" Glucocorticoid use in rheumatoid arthritis: Benefits, mechanisms, and

risks " :

www.clinexprheumatol.org/pdf/vol22/s35/s35_pdf/13townsend.pdf

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" The appropriate dose of corticosteroid will depend on the disease, its

severity and the clinical response obtained. In severe or life-threatening

illness such as SLE or vasculitis, high initial doses of corticosteroids

should be given to induce remission, possibly as intravenous pulses. The

dose should then be reduced gradually. Relapse may occur if the dose is

reduced too quickly. Much smaller steroid doses are appropriate for less

serious illness. In general, the aim should be to use the lowest dose that

will allow acceptable control of the disease. Prednisolone 15-20mg daily is

appropriate for initial treatment of polymyalgia rheumatica and 40mg daily

is sufficient for most cases of giant cell arteritis, although threatened

visual loss may require higher doses.

Corticosteroid pulse therapy has been used to induce remission in severe,

active rheumatoid disease. Its effects are short-lived and only high-dose

pulsed intravenous methylprednisolone, 1000mg x 3 over 72 hours, has been

shown to maintain remission until the delayed response to a new

disease-modifying drug started at the same time. In general, a daily dose of

more than 10mg prednisolone is rarely indicated for articular disease in

rheumatoid arthritis. "

Source:

Arthritis Research Campaign

" The Use and Abuse of Steroids in Rheumatology " :

http://www.arc.org.uk/about_arth/med_reports/series3/pp/6338/6338.htm

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" The usual dose of prednisone is 5 to 10mg daily. Although prednisone can

be started at higher doses (15 to 20mg daily), attempts should be made to

taper the dose over a few weeks to less than 10mg daily. Once started,

corticosteroid therapy is very difficult to discontinue and even at low

doses. Tapering of prednisone should be done slowly over a few weeks and

symptoms may reoccur with small changes in the prednisone dose.

Weight gain and cushingoid appearance is a frequent problem and source of

patient complaints. Recent studies have raised concern over accelerated

osteoporosis associated with low dose prednisone particularly at doses above

10 mg daily. Patients with and without osteoporosis risk factors on low dose

prednisone should undergo bone densitometry to assess fracture risk.

Bisphosphonates are recommended to prevent and/or treat osteoporosis.

Prednisone can also raise blood pressure and blood sugar levels. Recent

studies suggest, however, that low dose prednisone maybe effective as a

" disease modifying " agent in RA.

Higher doses of prednisone are rarely necessary unless there is a

life-threatening complication of RA and, if used for prolonged periods, may

lead to serious steroid toxicity. Although a few patients can tolerate every

other day dosing of corticosteroids which may reduce side effects, most

require corticosteroids daily to avoid symptoms. Once a day dosing of

prednisone is associated with fewer side effects than the equivalent dose

given bid or tid. Repetitive short courses of high-dose corticosteroids,

intermittent intramuscular injections, adrenocorticotropic hormone

injections, and the use of corticosteroids as the sole therapeutic agent are

all to be avoided. "

Source: s Hopkins Arthritis

http://www.hopkins-arthritis.som.jhmi.edu/rheumatoid/rheum_treat.html

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" Studies looking at low dose corticosteroid use, as low as 2.5 mg daily,

show an increase in bone loss and fracture risk (2,5). The risk of fracture

with corticosteroid use increases with higher doses of steroids. A

retrospective cohort study with over 244,000 corticosteroid users compared

to non-users showed that the relative risk of vertebral fracture in patients

taking daily prednisolone went from 1.55 (1.20-2.01) on less than 2.5 mg, to

2.59 (2.16-3.10) on 2.5-7.5 mg, and to 5.18 (4.25-6.31) on 7.5 mg or higher

(5). In another retrospective cohort study, the relative risk for fracture

in patients using greater than 10 mg prednisone daily, continuously for over

3 months, was 7.16 at the hip, and 16.94 at the lumbar spine, compared to

control patients who had never used oral corticosteroids (3).

The effect of low-dose corticosteroid therapy on BMD and fracture risk has

been most closely studied in specific patient populations. Many patients

with early diagnosis of rheumatoid arthritis are started on low-dose

corticosteroids, less than or equal to 5 mg daily, to prevent the

development of rheumatoid arthropathy. Even low-dose corticosteroids in

these patients have been shown to decrease BMD and increase fracture risk

(6). "

Source:

OsteoEd

" How does corticosteroid dose affect the risk of osteoporosis " :

http://osteoed.org/faq/secondary/dose_risk.html

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Not an MD

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org