Early use of hydroxychloroquine prevents damage accrual in systemic lupus erythematosus

Starting the antimalarial drug hydroxychloroquine (HCQ) (Plaquenil) early on in the disease process may help prevent damage accrual in patients with systemic lupus erythematosus (SLE). A new study, published in the May 2005 issue of Arthritis & Rheumatism, has demonstrated that HCQ appears to reduce the risk of damage accrual, provided the drug is initiated before damage has begun.

“This study suggests that patients with mild disease who are treated with HCQ do better in the long run than patients who were not treated with HCQ,” lead author of the study, Dr Barri Fessler (University of Alabama at Birmingham Health System), tells rheumawire. The results suggest that it might have a protective effect against certain lupus manifestations or complications from medications used to treat lupus. “Therefore, it should be more widely prescribed in lupus patients, [and] not only to those with the manifestations [that currently define its typical use].”Fessler comments that hydroxychloroquine “is typically used for treatment of joint pain and swelling, rashes, and fatigue associated with lupus. The dose is typically 200 mg once or twice daily [up to] 6.5 mg/kg per day.” HCQ is relatively safe, so patients can remain on this therapy as long as there is no evidence of toxicity. “A very rare side effect of treatment with hydroxychloroquine is retinopathy, and therefore it is recommended that patients have a baseline examination followed by regular exams by an ophthalmologist.”Previous studies have demonstrated that, in patients with SLE, HCQ is beneficial for the management of mucocutaneous manifestations, arthritis, and mild constitutional symptoms. Added benefits include reductions in serum cholesterol levels, protection against osteoporosis in patients taking corticosteroids, and a decrease in the frequency of lupus flares. What remained to be seen was whether HCQ could also reduce the risk of damage accrual in SLE patients.Follow-up in 518 patients To help answer this question, Fessler and colleagues conducted annual follow-ups of 518 patients who met at least four components of the American College of Rheumatology (ACR) criteria for SLE but had had the disease for only five years or less. Follow-up included measurements of clinical and serological manifestations of SLE as well as measurement of disease activity using the Systemic Lupus Activity Measure (SLAM) and measurement of damage using the Systemic Lupus International Collaborating Clinics damage index (SDI). Mean follow-up was nearly three years.At the time of enrollment, 56% of the 518 patients followed were being treated with HCQ. These patients had lower SLAM and SDI scores at the outset of the study than patients not taking HCQ. In addition, patients taking HCQ were significantly less likely to have major organ involvement, including renal disease (p<0.0001) and central nervous system disease (p<0.0025) at the study outset.Unadjusted analysis using a Cox proportional hazards model revealed that patients taking HCQ were less likely than those not receiving HCQ to accrue damage, with a hazard ratio (HR) of 0.68. After adjusting for differences at study enrollment between patients who received HCQ and those who did not, the HR for accruing damage among those taking HCQ, compared with those who were not, rose to 0.73 but remained significant at p=0.05. HCQ appeared to protect against damage accrual only in patients who did not have damage when they were initiated on the medication, however. Among patients taking HCQ who had no damage at the study outset, the HR for the risk of damage accrual was 0.55 (p=0.0111). Among those receiving HCQ who already had damage at the study outset, the HR was not statistically significant, at 1.106, p=0.6630. "Hydroxychloroquine should be started as treatment as soon as a diagnosis of lupus is established, regardless of its manifestations or severity, as it may help to prevent development of organ damage in the future," Fessler comments.(Source: Fessler BJ, Alarcon GS, McGwin G, et al. Systemic lupus erythematosus in three ethnic groups. XVI. Association of hydroxychloroquine use with reduced risk of damage accrual. Arthritis Rheum. 2005; 52:1473-1480: Joint and Bone.)