Hydroxychloroquine in systemic lupus erythematosus: overview of current knowledge

Abstract

The antimalarial hydroxychloroquine (HCQ) has demonstrated several crucial properties for the treatment of systemic lupus erythematosus (SLE). Herein, we reviewed the main HCQ pharmacologic features, detailed its mechanism of action, and summarized the existing guidelines and recommendations for HCQ use in rheumatology with a systematic literature search for the randomized controlled trials focused on lupus. HCQ has been shown to decrease SLE activity, especially in mild and moderate disease, to prevent disease flare and to lower the long-term glucocorticoid need. The numerous benefits of HCQ are extended to pregnancy and breastfeeding period. Based on cohort studies, antithrombotic and metabolic HCQ’s effects were shown, including lipid-lowering properties, which might contribute to an improved cardiovascular risk. Moreover, early HCQ use in antinuclear antibodies positive individuals might delay the progression to SLE. Finally, HCQ has a significant favorable impact on long-term outcomes such as damage accrual and mortality in SLE. Based on these multiple benefits, HCQ is now the mainstay long-term treatment in SLE, recommended by current guidelines in all patients unless contraindications or side effects. The daily dose associated with the best compromise between efficacy and safety is matter of debate. The concern regarding retinal toxicity rather than proper efficacy data is the one that dictated the daily dosage of ⩽5 mg/kg/day actual body weight currently agreed upon.

EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update

“…Thus, hydroxychloroquine may be used in patients with early, mild disease (ie, without poor prognostic factors) in whom the other three csDMARDs are contraindicated or not tolerated. Of note, hydroxychloroquine is widely used in other diseases, especially SLE, 34 but not for the purpose of inhibiting joint damage progression. Consequently, this drug is not mentioned among the recommendations, because the task force did not wish to suggest that MTX could be replaced by hydroxychloroquine.…”

Recent Advances in SLE Treatment Including Biologic Therapies

“…Studies indicate that antimalarials reduce mortality in SLE patients of diverse ethnic groups [34][35][36][37][38]. Administration of HCQ significantly reduces the severity of SLE disease activity, which includes a reduction in active clinical involvements, serum markers, activity scores, and disease flares [39]. Randomized controlled trials (RCT) have demonstrated the benefits of HCQ in SLE, including a reduction in flares [40][41][42], improvement in arthralgia [41], cytokine profiles [29,[43][44][45], and disease severity [36,[46][47][48][49].…”

“…Randomized controlled trials (RCT) have demonstrated the benefits of HCQ in SLE, including a reduction in flares [40][41][42], improvement in arthralgia [41], cytokine profiles [29,[43][44][45], and disease severity [36,[46][47][48][49]. HCQ decreases SLE disease activity, including flares during pregnancy [39,50]. Despite the fact that HCQ is well tolerated, it has been linked to a variety of side effects, including cardiovascular, hematological, neurological, ocular, and skin concerns [39].…”

Knowledge of Saudi Patients with Autoimmune Diseases about Hydroxychloroquine Toxicity: The Role of Physician–Patient Communication

“…Currently, hydroxychloroquine (HCQ), is a hydroxylated chloroquine derivative which was designed to treat malaria. HCQ is also used to manage autoimmune conditions including SLE, as monotherapy or in combination with other agents when there are no contraindications [ 3 ].…”