The toxic effects of chloroquine and hydroxychloroquine on skeletal muscle: a systematic review and meta-analysis

Abstract

The aim of this systematic review was to perform qualitative and quantitative analysis on the toxic effects of chloroquine (CQ) and hydroxychloroquine (HCQ) on skeletal muscles. We designed the study according to PRISMA guidelines. Studies for qualitative and quantitative analyses were selected according to the following inclusion criteria: English language; size of sample (> 5 patients), adult (> age of 18) patients, treated with CQ/HCQ for inflammatory diseases, and presenting and not presenting with toxic effects on skeletal muscles. We collected data published from 1990 to April 2020 using PubMed, Cochrane Library, EMBASE, and SciELO. Risk of bias for observational studies was assessed regarding the ROBIN-I scale. Studies with less than five patients (case reports) were selected for an additional qualitative analysis. We used the software Comprehensive Meta-Analysis at the confidence level of 0.05. We identified 23 studies for qualitative analysis (17 case-reports), and five studies were eligible for quantitative analysis. From case reports, 21 patients presented muscle weakness and confirmatory biopsy for CQ/HCQ induced myopathy. From observational studies, 37 patients out of 1,367 patients from five studies presented muscle weakness related to the use of CQ/HCQ, and 252 patients presented elevated levels of muscle enzymes (aldolase, creatine phosphokinase, and lactate dehydrogenase). Four studies presented data on 34 patients with confirmatory biopsy for drug-induced myopathy. No study presented randomized samples. The chronic use of CQ/HCQ may be a risk for drug-induced myopathy. There is substantiated need for proper randomized trials and controlled prospective studies needed to assess the clinical and subclinical stages of CQ/HCQ -induced muscle myopathy.

Figure 1

Flow diagram of the literature search strategy and eligibility.

Figure 2

(a) Forest plot for variable: reported clinic symptoms of QC/HQC related muscle toxicity. (b) Forest plot for variable: Laboratorial findings of elevated muscle enzyme levels in patients treated with QC/HQC. (c) Forest plot for variable: Confirmatory Biopsy for Drug-induced myopathy. CI confidence interval.

Figure 3

(A) Bias domains in ROBINS-I for included studies. (B) Total Score for each domain (ROBINS-I).

Figure 4

Hypothesis for combined effects of sarcopenia and CQ/HCQ induced myopathy along with aging and chronic use of drugs.