Quinacrine added to ongoing therapeutic regimens attenuates anticardiolipin antibody production in SLE

Abstract

The benefit of combining quinacrine (Qn) with hydroxychloroquine (HCQ) in the treatment of systemic lupus erythematosus (SLE) was previously re-evaluated by us. In our current study we observed that, in 11 active SLE patients (SLEDAI score 5-12), the addition of Qn (100 mg/day) to their existing ongoing therapeutic regimens resulted in a significant attenuation of their previously persistent anticardiolipin antibody (aCL) response. This was in comparison with a matched non-Qn treated control group composed of 14 randomly chosen aCL-positive SLE patients with a similar SLEDAI score 6-10. Prior to Qn treatment the therapeutic regimens of 12 months' duration, included in all cases HCQ (400 mg/day), in many cases prednisone (P, 10-20 mg/day) and in some additional cases immunosuppressive drugs. SLEDAI scores and aCL levels were monitored during the entire follow-up period which totaled 24 months in the study group and 15-18 months in the controls. Along with the beneficial effect of the added Qn on SLEDAI scores, aCL disappearance was documented in eight of 11 patients and remained negative during 8-12 months of follow-up (P = 0.004), compared with such a change in only three of 14 non-Qn treated aCL-positive patients (P = 0.18). We conclude that the added Qn treatment to former established therapeutic protocols may eliminate aCL response in SLE patients. Whether this agent's effect is permanent needs further elucidation.

The Reduction of Serum B‐Lymphocyte Activating Factor levels following Quinacrine Add‐On Therapy in Systemic Lupus Erythematosus

“…In our previous study, we have shown that add-on Qn decreased SLEDAI scores and was of steroid sparing effect in SLE [12]. In a further study, we were also able to show that Qn treatment attenuated long-lasting aCL titres in SLE patients [24]. The reduction effect of this regimen on both serum BAFF and aCL should encourage more frequent usage of Qn in the treatment of SLE patients.…”

Management of the antiphospholipid syndrome

“…In the Baltimore Lupus Cohort, hydroxychloroquine use was found to be protective in reducing the risk for future thrombus; however, it was not clear if hydroxychoroquine was a primar y factor [40]. In a recent clinical trial, addition of quinacrine to SLE aCL-positive patients being treated with hydroxychloroquine resulted in disappearance of the aCL in eight of 11 study subjects (P = 0.004) compared with only three in 14 nonquinacrine treated controls (P = 0.18) [42]. There have been safety concerns about the use of hydroxycholoquine in pregnancy; however, a recent review of hydroxychloroquine use in pregnancy did not find any increase in the rate of birth defects in more than 250 pregnancies in which hydroxychloroquine was used for an underlying connective tissue disease [43].…”

Management of antiphospholipid syndrome

“…This agent also appears to decrease aCL levels in humans [Toubi et al 2003]. No teratogenicity has been described with the use of hydroxychloroquine in pregnant women with SLE [Motta et al 2005;Khamashta et al1996;Parke and West, 1996]; however, the safety and efficacy of this drug in pregnant women with APS have not been examined in large clinical trials.…”