Minocycline fails as systemic sclerosis treatment

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Rheumawire

Feb 19, 2004

Minocycline fails as systemic sclerosis treatment

Houston, TX - An open-label trial of over 30 patients has not confirmed

earlier suggestions that minocycline might improve skin thickness in

systemic sclerosis. Dr Maureen D Mayes (University of Texas-Houston

Health Science Center) reports in the February 2004 issue of Arthritis &

Rheumatism that skin changes in the treated patients were quite similar

to those reported in a previous, negative study using D-penicillamine

[1,2]. The small degree of skin-thickness improvement in both trials was

judged to reflect changes associated with the natural history of the

disease, in which skin thickness typically increases over the first 2 to

5 years, then gradually improves.

" Skin scores in the minocycline group changed over time at the rate

predicted by the D-penicillamine trial. This is strong evidence against

a minocycline treatment effect, " writes Mayes. She also notes that an

open-label trial like this one would be expected, if anything, to

exaggerate any treatment effect.

The patients in this trial all had diffuse systemic sclerosis of 5 years

or less duration and were treated with oral minocycline for 1 full year

(50 mg bid for 1 month, then 100 mg bid for 11 months). Of the 36

patients enrolled, 31 returned for at least 1 assessment 3 months or

more after study entry and were included in the intent-to-treat

evaluation. About half of these patients did not complete all 12 months

of treatment; most (10) withdrew due to disease progression.

The primary outcome measure was the degree and extent of skin

thickening, scored using the modified Rodnan skin-thickness score

(MRSS). The mean MRSS at entry was 22.7 (range 12-43). Mean MRSS at the

final visit was 18.6 (range 2-48).

" There was no statistically significant difference in the change in skin

scores between the minocycline-treated subjects and subjects previously

reported in the D-penicillamine trial. In addition, when adjusted for

disease duration, a comparison of MRSS in the minocycline-trial subjects

(including all subjects active at each time point) and the previously

reported D-penicillamine trial subjects showed no difference and no

treatment effect, " the investigators write.

The patients who dropped out of the Mayes trial before completing 1 year

of treatment had significantly " newer " systemic sclerosis than those who

completed the study (mean 16.0 vs 29.8 months, p<0.03). This suggests

that the completers had reached the disease stage often characterized by

some spontaneous regression of skin thickening and continued with

treatment in the hope that the change was due to minocycline. In fact,

there was a change of 7.3 MRSS units in the completers (vs 0.2 in the

noncompleters), but this fell within the expected normal variation of

the disease.

Similarly, there were no significant effects on the secondary outcome

measures of right hand extension, left hand extension, or oral aperture.

Taking the natural history of systemic sclerosis into consideration,

Mayes et al had set a 30% decrease in MRSS as the minimum change that

could be interpreted as a positive result. " It is crucial to emphasize

that open-label trials in systemic sclerosis must take into

consideration the expected improvement in skin scores so as not to

systematically overestimate a treatment effect, " they warn.

Janis

Sources

1. Mayes MD, O'Donnell D, Rothfield NF, Csuka ME. Minocycline is not

effective in systemic sclerosis: Results of an open-label multicenter

trial. Arthritis Rheum 2004 Feb; 50(2):553-7.

2. Clements PJ, Furst DE, Wong WK, et al. High-dose versus low-dose

D-penicillamine in early diffuse systemic sclerosis: analysis of a

two-year, double-blind, randomized, controlled clinical trial. Arthritis

Rheum 1999 Jun; 42(6):1194-203.

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org