Dehydroepiandrosterone in the treatment of systemic lupus erythematosus

R. F. van Vollenhoven

Department of Rheumatology, D2-1, Karolinska Hospital, Stockholm, S-17176, Sweden

SIR, I would like to thank Drs Isenberg and Ramsey-Goldman for their detailed review of disease assessment in systemic lupus erythematosus (SLE) [1]. Included under the heading Future developments is a reference to a recent study with dehydroepiandrosterone (DHEA) in severe SLE [2], which as they correctly point out, did not support a major therapeutic role for this agent in severe SLE. However, in the context of outcome assessment in SLE, it may be of interest to the readers of Rheumatology that two large clinical trials of DHEA (GL701) for moderately active SLE have been completed recently, both of which used novel methods of assessing therapeutic success in SLE that had not previously been used in large clinical trials. In the first trial, reported in abstract form [3], patients deemed corticosteroid-dependent were included in the study, and the primary outcome was ability to taper corticosteroids to a physiological level (prednisone <=7.5 mg/day) after 7–9 months. In order to measure this outcome, a corticosteroid tapering regimen was required for patients having stable or improved SLE disease activity (as measured by SLEDAI). The study showed that patients with active SLE were able to achieve the primary goal more frequently when on active medication compared with placebo. More pertinent to the paper of Isenberg and Ramsey-Goldman, the study showed that an assessment of therapeutic efficacy based on the steroid-sparing potential of an agent can be carried out in a multicentre, randomized, double-blinded fashion, using this blueprint. Moreover, in this trial the thorny issue of defining SLE flares was sidestepped by referring to increases in SLEDAI scores, which could in clinical reality be perceived as flares.

In the second trial, the effect of DHEA/GL701 on overall SLE activity was assessed by defining a responder index based on the SLAM score, SLEDAI score, patient global index and prednisone dose. A patient was considered a responder if all four of these were improved or at least unchanged (within the margin of variability of these outcomes). Results of this trial have not yet been reported, but a recent press release indicated that the number of responders was significantly higher among the patients on active treatment, suggesting that this method of ascertaining treatment response was succesful and appropriate for the agent under investigation.

Thus, each of these two clinical trials, in addition to the main purpose of defining the role of DHEA in the treatment of SLE, will provide valuable information on the use of two possible new ways in which the efficacy of a therapeutic agent in SLE can be assessed. Inasmuch as these two trials have included approximately 200 patients each and are therefore the largest randomized clinical trials ever performed in SLE, it is likely that this information will also help advance the methodology of clinical studies in SLE.

References

  1. Isenberg D, Ramsey-Goldman R. Assessing patients with lupus: towards a drug responder index. Rheumatology1999;38:1045–9.[Free Full Text]
  2. Van Vollenhoven RF, Park JL, Genovese MC et al. A double-blind, placebo-controlled, clinical trial of dehydroepiandrosterone in severe systemic lupus erythematosus. Lupus1999;8:181–7.[ISI][Medline]
  3. Petri M, Lahita R, McGuire J et al. Results of the GL701 (DHEA) multicenter steroid-sparing SLE study. Arthritis Rheum1997;40:S327.
Accepted 15 February 2000





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