Session Information
Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: Although existing evidence demonstrates the efficacy of antimalarials for rheumatic skin disease, the safety of these medications, and particularly quinacrine, remain debated. Quinacrine may soon become increasingly difficult to prescribe as a result of these concerns. We investigate the toxicity risk associated with various antimalarial combinations in rheumatic skin disease patients.
Methods: 532 patients (mean age=52.29 years, female=85.15%, male=14.85%) were selected from two ongoing databases of cutaneous lupus erythematosus (69.92%) and dermatomyositis (30.08%). Details regarding antimalarial treatment and toxicities were extracted and five different treatment courses were defined [i.e., hydroxychloroquine, chloroquine, and quinacrine monotherapies, as well as hydroxychloroquine+quinacrine and chloroquine+quinacrine combinations]. The hazard ratio of each major toxicity on the five different treatment courses was estimated using the Cox proportional hazard model to compare the risk associated with each type of treatment to that of hydroxychloroquine.
Results:
Over 90% of patients had a history of hydroxychloroquine, and nearly half (42.9%) had a history of hydroxychloroquine+quinacrine. Only 21.3% of patients had a history of chloroquine either as monotherapy (11.1%) or as chloroquine+quinacrine combination (10.2%). Over half of the patients had a history of quinacrine, usually in combination with hydroxychloroquine or chloroquine, but also as monotherapy (11.8%).
The most prevalent side effects included cutaneous eruption (n=61), gastrointestinal upset (n=38), mucocutaneous dyspigmentation (n=26), neurologic toxicities [i.e., including dizziness and headache (n=10), ototoxicity (n=5), sleep disturbances (n=5), mental fog (n=5), peripheral neuropathy (n=4), tremors (n=2), and psychosis (n=1)], and retinopathy (n=17). Compared to hydroxychloroquine, the hazards of cutaneous eruption, gastrointestinal upset, and neurologic toxicities were lower with hydroxychloroquine+quinacrine. However, based on a post-hoc analysis, this may represent the selection of patients able to tolerate hydroxychloroquine in the cohort of those who received hydroxychloroquine+quinacrine. Although there was increased risk of retinopathy with chloroquine and chloroquine+quinacrine relative to hydroxychloroquine, ophthalmic toxicity was not seen with quinacrine (Table I).
Conclusion: Our study provides evidence that the safety profile of quinacrine is comparable to that of first-line hydroxychloroquine and that quinacrine has an advantage over hydroxychloroquine and chloroquine for patients at risk of retinopathy. Furthermore, adding quinacrine to hydroxychloroquine or chloroquine does not increase the risk of toxicities, and limiting access to quinacrine may leave patients without alternatives to this safe drug.
Table I.
|
Treatment Course |
Adjusted HRa |
95% Confidence Interval for Adjusted HR |
Un-adjusted HR |
95% Confidence Interval for Un-adjusted HR |
|
Chloroquine |
|
|
|
|
|
Skin Eruption |
0.277 |
0.038-2.028 |
0.563 |
0.135-2.341 |
|
Dyspigmentation |
† |
|
† |
|
|
GI Upset |
0.400 |
0.054-2.961 |
0.354 |
0.048-2.606 |
|
Neurologic |
† |
|
† |
|
|
Ophthalmic |
30.349 **** |
2.588-355.887 |
12.880 ** |
1.789-92.723 |
|
Quinacrine |
|
|
|
|
|
Skin Eruption |
† |
|
† |
|
|
Dyspigmentation |
4.047 |
0.956-17.139 |
3.278 |
0.787-13.646 |
|
GI Upset |
1.273 |
0.380-4.266 |
1.028 |
0.312-3.388 |
|
Neurologic |
0.459 |
0.061-3.461 |
0.455 |
0.061-3.386 |
|
Ophthalmic |
† |
|
† |
|
|
HCQ+Quinacrine |
|
|
|
|
|
Skin Eruption |
0.231 **** |
0.082-0.651 |
0.236 **** |
0.084-0.664 |
|
Dyspigmentation |
1.517 |
0.485-4.746 |
1.416 |
0.462-4.343 |
|
GI Upset |
0.260 ** |
0.078-0.863 |
0.227 ** |
0.069-0.747 |
|
Neurologic |
0.195 ** |
0.045-0.840 |
0.199 ** |
0.047-0.845 |
|
Ophthalmic |
2.248 |
0.136-37.028 |
1.152 |
1.104-12.753 |
|
CQ+Quinacrine |
|
|
|
|
|
Skin Eruption |
0.849 |
0.260-2.771 |
0.865 |
0.266-2.812 |
|
Dyspigmentation |
1.299 |
0.160-10.529 |
1.234 |
0.154-9.878 |
|
GI Upset |
0.446 |
0.060-3.314 |
0.170 |
3.001 |
|
Neurologic |
0.471 |
0.063-3.519 |
0.451 |
0.061-3.345 |
|
Ophthalmic |
26.664 **** |
2.723-261.101 |
13.578 **** |
2.261-81.548 |
|
HCQ = hydroxychloroquine; CQ = chloroquine; HCQ+Quinacrine = hydroxychloroquine+quinacrine; CQ+Q = chloroquine+quinacrine a = Cox proportional hazard ratios (HR) of toxicities while on various antimalarial regimens, with risk of toxicities on hydroxychloroquine monotherapy as the reference level; adjusted for sex, age, race, and smoking status (never vs. current and past smokers) ** P < 0.05 **** P < 0.01 † = No observations of toxicity |
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To cite this abstract in AMA style:
Mittal L, Zhang L, Feng R, Werth V. Antimalarial Drug Toxicities in Rheumatic Skin Disease Patients [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/antimalarial-drug-toxicities-in-rheumatic-skin-disease-patients/. Accessed .« Back to 2017 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/antimalarial-drug-toxicities-in-rheumatic-skin-disease-patients/