Hydroxychloroquine and COVID-19: a Rheumatologist’s Take on the Lessons Learned

Abstract

Purpose of Review Told from the viewpoint of rheumatologists, this review tells the story of hydroxychloroquine and its swift ascent to become a household name as a therapeutic strategy against the novel SARS-CoV-2 virus. This review describes the history, mechanisms, pharmacokinetics, therapeutic applications, and safety profile of hydroxychloroquine as an immunomodulatory and antiviral agent. It also summarizes the major studies that launched and assessed the use of hydroxychloroquine against COVID-19 infection. Recent Findings More recent literature calls into question the long-held dogma that endolysosomal alkalinization is the primary mode of action of hydroxychloroquine. Ongoing uncertainty about the multiple potential mechanisms contributing to the therapeutic effect of hydroxychloroquine in rheumatic and viral disease led to a natural avenue for exploration in the treatment of COVID-19. Taken as a whole, the literature does not support utilizing hydroxychloroquine to treat or prevent infection from the SARS-CoV-2 virus. This is, at least in part, due to the wide variability in hydroxychloroquine pharmacokinetics between patients and difficulty achieving adequate target tissue concentrations of hydroxychloroquine without encountering unacceptable toxicities. Summary Hydroxychloroquine continues to be a routinely prescribed, well-tolerated, effective, and low-cost treatment for rheumatic disease. Its therapeutic versatility has led to frequent repurposing for other conditions, most recently as an investigative treatment against the SARS-CoV-2 virus. Despite overall negative findings, the intense study of hydroxychloroquine against COVID-19 infection has enhanced our overall understanding of how hydroxychloroquine operates in autoimmune disease and beyond.

Knowledge mapping of COVID-19 and autoimmune diseases: a visual and bibliometric analysis

“…The effects on cytokine production and antigen presentation inhibition may have immunological consequences, such as blocking innate and adaptive antiviral immune responses in COVID-19 patients, making the use of HCQ controversial [ 40 , 47 – 49 ]. However, the study of HCQ in COVID-19 has allowed researchers to deepen their understanding of how HCQ plays a role in ADs and other diseases [ 50 ]. As for rituximab, it is a chimeric monoclonal antibody against CD20-positive B lymphocytes, and B cell-targeting strategies such as rituximab are widely used in B-cell hematological malignancies, rheumatic and musculoskeletal diseases, and various Ads [ 51 , 52 ].…”

Extrapolation of Adult Efficacy Data to Pediatric Systemic Lupus Erythematosus: Evaluating Similarities in Exposure–Response

“…Hydroxychloroquine is an antimalarial drug with multiple proposed mechanisms of action in SLE, including inhibiting Toll‐like receptor signaling and autoantigen presentation, and reducing B‐cell and T‐cell activation 15 . Hydroxychloroquine is FDA approved for the treatment of SLE in adults and is used extensively off‐label in children with SLE.…”

Repurposed and investigational disease-modifying drugs in osteoarthritis (DMOADs)

“…HCQ belongs to the group of antimalarial agents, was synthesized in 1946 and is currently used in various rheumatic and skin diseases since its first approval in 1955 by FDA. 92 , 93 It possesses anti-inflammatory actions such as decreasing cytokine production from T cells and monocytes, especially IL-1 and IL-6. 94 In the first randomized controlled trial (RCT) conducted in hand OA and published in 2018, administration of oral 400 mg HCQ once a day for 24 weeks is not superior to placebo in improving symptomatic hand OA at weeks 6, 12 and 24 ( n = 196).…”