Our prospective analysis presents evidence of response to antimalarials, without concomitant immunosuppressive or immunomodulator use, in a CLE population seen at an academic referral center.
In our patients initiated on hydroxychloroquine, about half demonstrated improvement at their first follow-up visit. Our response rate is similar to that of a multicenter randomized controlled trial comparing hydroxychloroquine to acetretin, in which 50% of CLE patients on hydroxychloroquine improved at 8 weeks based on clinical parameters10
. In the discoid LE population, response to antimalarials has been cited to occur in 95% of patients and response to hydroxychloroquine in 70%11, 31
, though the latter was studied in a non-referral dermatological setting. This suggests that our referral population is more antimalarial-resistant than the non-referral population18
In patients who failed hydroxychloroquine, we detected a significant reduction in CLASI activity scores with initiation of hydroxychloroquine-quinacrine, which supports Cavazzana et al
’s work that demonstrated improvement with hydroxychloroquine-quinacrine therapy by using an unvalidated method of retrospectively assigning CLASI scores13
. Additionally, for non-responders at the first follow-up visit following initiation of hydroxychloroquine-quinacrine, we found a decrease in CLASI activity scores for almost all patients, despite their not meeting response criteria. For those with further follow-up, a continued decrease in scores was observed (). Also, patients with consistently mild disease while taking hydroxychloroquine demonstrated response with the addition of quinacrine (), suggesting that adding quinacrine could be helpful in mild patients who desire improvement.
Forty percent of patients continued on either hydroxychloroquine or hydroxychloroquine-quinacrine demonstrated response with continuation of their respective antimalarial therapy. One out of 5 initial non-responders to hydroxychloroquine and 2 out of 5 initial non-responders to hydroxychloroquine-quinacrine were responders with continuation of their respective antimalarial therapy (, ). These data support the recommendation of continuing patients on antimalarial therapy beyond 2 months, even if they do not initially demonstrate improvement6
Two previous papers have addressed the use of chloroquine-quinacrine combination therapy. Feldmann et al
found skin lesions improved significantly or cleared totally in all SCLE and one-half of chronic LE patients14
. Lipsker et al
found that three-quarters of DLE, all SCLE, and all DLE/SCLE patients demonstrated complete or greater than 50% clearance of lesions15
. Our response rate is not as high as those reported in these two studies, which may be a reflection of differences in antimalarial use. None of the patients in these two studies had been on a trial of hydroxychloroquine-quinacrine before starting chloroquine-quinacrine, which is in contrast to our patients who had all failed hydroxychloroquine-quinacrine in the past.
There are several limitations to our study. As a result of both small sample size and a wide range of CLE subtypes, we could not draw any conclusions regarding differences in treatment response based on CLE subtype. Larger studies are necessary to evaluate response to antimalarials and any differences across CLE subtypes. In using both change and percent change criteria to determine response28
, it became apparent that percent change may not be as meaningful with very low (e.g. 0, 1) and high CLASI scores. Studies to evaluate the use of the CLASI across disease severity subtypes would be helpful in determining when change or percent change is most appropriate to use. Additionally, when the criteria for response were determined, high specificity was favored to minimize the misclassification of patients as responders who did not experience a true clinical improvement28
. As such, the sensitivity is lower, increasing the number of patients classified as non-responders who did experience a true clinical improvement. Lastly, in our referral population, we see a wide variety of CLE subtypes18
and are more likely see treatment-resistant patients. Although this selection bias limits the generalizability of our results, it allows us to better characterize treatment response in an antimalarial-resistant population and understand which patients will benefit from immunosuppressives, immunomodulators, or investigational therapies.
Overall, this prospective study provides evidence supporting the use of hydroxychloroquine-quinacrine for treating CLE patients who do not respond to hydroxychloroquine. It also demonstrates that continuing patients on hydroxychloroquine or hydroxychloroquine-quinacrine can be beneficial, even in the absence of initial response.