Session Information
Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: To determine the efficacy and adverse effects of antimalarials in patients with systematic lupus erythematosus (SLE).
Methods: A literature search from inception to December 2016 was performed using MEDLINE, EMBASE, Cochrane, CINAHL and ClinicalTrials.gov. All randomized control trials, clinical control trials, cohort, case control and cross-sectional studies of interest were included. Duplicate, independent screening of titles and abstracts was done to identify relevant studies. The primary outcome were effects of antimalarials (AMs) on lupus activity, irreversible organ damage, survival and adverse effects. Secondary outcomes were thrombosis, atherosclerosis, cardiovascular disease, neuro-psychiatric disease, effect on bone metabolism.
Results: 5364 abstract and titles were screened for studies assessing the efficacy and toxicity of antimalarial therapy in patients of SLE. 406 full texts were screened and 51 studies with 17349 patients qualified for final analyses. Mean ages were 6-70 years and mean follow-up was 6 months to 10 year.
We found that antimalarials significantly reduce the number of flares and disease activity in SLE patients (high level evidence). Patients on HCQ have increased odds of achieving remission (weak evidence) (Table 1). Outcomes remained similar and significant in pregnant women. We also found that antimalarials have significant toxic effects on skin, eyes and GI tract. Of these, most severe is retinal toxicity which is more evident in patients on Chloroquine as compared to HCQ (p=0.001). Risk of retinal toxicity is more at high doses of chloroquine (>4 mg/kg/day) and longer duration exposure (>7 years). We found weak evidence for antimalarials in preventing/delaying development of new organ damage in patients with SLE. High evidence was found for role of AMs in reducing the risk of mortality in patients with SLE (HR, 0.32 95% CI 0.16 to 0.66, I2 of 81%; 4 studies). Antimalarial use also improves lipid profile, bone mineral density and have better cardiovascular outcomes (data is not presented).
Conclusion: Broad spectrum effects and safety profile of AMs qualifies them as a drug of choice in management of patients with SLE. They are effective in preventing flares, reducing systemic disease activity, mortality and have also shown preventive effect on irreversible end organ damage in SLE patients. They do have some adverse effects on long term use, which can be prevented by appropriate screening practices and using less toxic formulations like hydroxychloroquine.
Table 1: Summary of results for major outcomes
|
Outcome |
Number of studies |
Design of Included studies |
Number of participants |
Age range (mean) |
Gender |
Results |
|
SLE activity |
23 |
5 RCT; 16 cohort; 1 cross sectional and 1 case control study |
4849 |
17 -70 years |
Females:4278; Males: 485 |
Low SLE disease activity is associated with high serum HCQ concentration based on data from three studies (p <0.0001; p=0.005; p=0.04). AMs use reduce SLICC/ACR DAI (r=0.22, p=0.015), SLAM R (p=0.0157, and p <0.001) sores and general symptoms and swollen/painful joint counts (p=0.02). Flares on AMs: A randomized trial showed that patients on antimalarials have significantly less numbers of SLE flares (defined by American Rheumatic association criteria)(p<0.02). Antimalarial drugs increase the odds of clinical quiescent phase (HR, 2.8 95% CI 1.4 to 5.57, p=0.004). In one cohort study patients with high number of flares during follow up had significantly low serum concentration of HCQ (p=0.006). On multivariate analysis low HCQ concentration is a risk factor for SLE flares (OR: 3.82, 95% CI 1.16 to 2.58, p=0.027. One trial showed significantly lower incidence of disease exacerbation in chloroquine group as compared to placebo (p<0.01). Remission: Antimalarial use was significantly associated with remission in SLE patients (OR: 12.91, 2.87 to 58.13). HCQ vs Corticosteroids: HCQ have less number of flares, severity of flare and better economic outcomes as compared to patients on corticosteroids. HRQOL: Blood HCQ concentration is not predictive of HRQOL. Pregnancy outcomes: Holding HCQ during pregnancy can lead to 3.6 times more flares and use of HCQ during pregnancy have significant improvement in SLEDAI score during pregnancy (p<0.038). Time lag: In one study early HCQ use was associated with increase time lag between 1st symptom and full SLE criteria as compared to controls (p<0.018). |
|
Adverse reactions |
17 |
1 RCT, 4 case control studies, 9 cohort studies and 3 cross sectional |
3893 |
6-56 years |
Females 2470; Males: 1423 |
Cutaneous side effects: Three studies described cutaneous pigmentation as adverse effect of antimalarials. In one case control study, 159/209 chloroquine users had skin toxicity. Cardiotoxicity: No significant changes in heart rate, premature beats, heart rate variability and repolarization after treatment with chloroquine. Retinal toxicity: Retinopathy developed in 21 out of 85 patients (24.7%), patients on CQ (13) had significantly higher risk compared to on HQ(8) treatment (p=0.001). In two studies, 2/58 and 7/2000 developed retinal toxicity with the use of HCQ. Risk of retinal toxicity increase significantly after 7 years of exposure. Retinal nerve fibre layer thickness: Patients on Chloroquine in dose of 4mg/kg/day have significantly lower thickness. Retinal function improves after discontinuations of drug for 6 months. All adverse effect: One trial and one retrospective cohort study showed that HCQ is associated with dermatological, gastrointestinal and ocular toxicity. Significant difference between incidence of HCQ and CQ toxicities was found (p<0.00001). |
|
Irreversible organ damage |
6 studies |
6 cohort studies |
5107 |
36 to 44.1 years |
Females: 4573, Males: 534 |
HCQ user have low hazard ratio for development of new organ damage (SDI score); HR 0.57, 95% 0.37 to 0.88. Similarly, HCQ delays the time to first change in SDI score. Non-AM user have longer disease (p=0.004) duration and high SDI (p<0.001). Based on data from two cohort studies showed that HCQ use was associated with reduced risk for new organ damage (SDI >/= 1), but the results did not reach statistical significance. |
SLICC/ACR DAI: Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index for SLE; SLAM-R: Systemic lupus activity measure-Revised; BILAG: The British Isles Lupus Assessment Group index; DAI: Disease Activity Index; HRQOL: Health related quality of life
To cite this abstract in AMA style:
Sharma G, Singh JA, Khaleel MS, Shrestha S. Efficacy and Toxicity of Antimalarials in Systematic Lupus Erythematosus: A Systematic Review [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/efficacy-and-toxicity-of-antimalarials-in-systematic-lupus-erythematosus-a-systematic-review/. Accessed .« Back to 2017 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/efficacy-and-toxicity-of-antimalarials-in-systematic-lupus-erythematosus-a-systematic-review/