Hydroxychloroquine/chloroquine and the risk of acute kidney injury in COVID-19 patients: a systematic review and meta-analysis.
Renal failure. 2022;(1):415-425
OBJECTIVES Hydroxychloroquine/chloroquine has been widely used as part of the standard treatment for patients with coronavirus disease 2019 (COVID-19). We conducted a systematic review and meta-analysis to determine whether hydroxychloroquine/chloroquine increases the risk of acute kidney injury (AKI) in COVID-19 patients. METHODS PubMed and Embase were searched for related publications from inception to Dec 31, 2021, including randomized controlled trials (RCTs) and non-randomized studies of interventions (NRSIs) comparing the risk of AKI and/or increased creatinine in COVID-19 patients receiving hydroxychloroquine/chloroquine and other controls (active treatment and placebo). We conducted separate meta-analyses for RCTs and NRSIs based on fixed-effect model, with odds ratios (ORs) being considered as effect sizes. RESULTS We included 21 studies in the analysis, with 12 were RCTs. Based on the RCTs, compared to placebo, the OR was 1.19 (95% confidence interval [CI]: 0.86, 1.64; p = .30, n = 4, moderate quality) for AKI and 1.00 (95%CI: 0.64, 1.56; p = .99, n = 5, moderate quality) for increased creatinine for patients received hydroxychloroquine/chloroquine treatment; compared to active treatment, the odds was 1.28 (95%CI: 0.65, 2.53; p = .47, n = 2, low quality) for AKI and 0.64 (95%CI: 0.13, 3.20; p = .59, n = 1, low quality) for increased creatine. Evidence from NRSIs showed slightly increased odds of AKI, with low quality. CONCLUSION Based on current available studies which were graded as low to moderate quality, there is insufficient evidence to conclude that hydroxychloroquine/chloroquine use is associated with increased risk of AKI or raised creatinine. Abbreviations: AKI: acute kidney injury; COVID-19: Coronavirus Disease 2019; RCT: randomized controlled trials; NRSI non-randomized studies of interventions; OR: odds ratios; ROBIS-I: Risk Of Bias In Non-randomized Studies - of Interventions.
Coronavirus disease 2019 (COVID-19) in a patient with ankylosing spondylitis treated with secukinumab: a case-based review.
Rheumatology international. 2020;(10):1707-1716
Severe acute respiratory syndrome coranovirus-2 (SARS-CoV-2) infection has become an important health-care issue worldwide. The coronavirus disease 2019 (COVID-19) has also raised concerns among patients with inflammatory rheumatic conditions and their treating physicians. There are emerging data regarding the potential risks of SARS-CoV-2 for this particular patient group. However, less is known with regard to the course of COVID-19 among patients receiving IL-17 inhibitors. The aim of the current article is to review the growing body of knowledge on the course/management of COVID-19 in patients with inflammatory rheumatic diseases by presenting a SARS-CoV-2 infected case with ankylosing spondylitis under secukinumab therapy. A 61-year old patient with ankylosing spondylitis who was on secukinumab therapy for 5 months admitted with newly onset fever and gastrointestinal complaints. After being hospitalized, she developed respiratory manifestations with focal pulmonary ground-glass opacities and multiple nodular densities in both lungs. The patient was tested positive for SARS-CoV-2 infection. Substantial clinical improvement was obtained following a management plan, which included tocilizumab, hydroxychloroquine, prednisolone and enoxaparin sodium. PubMed/MEDLINE and Scopus databases were searched by using relevant keywords and their combinations. The literature search revealed four articles reporting the clinical course of COVID-19 in seven rheumatic patients on secukinumab. The clinical course of SARS-CoV-2 infection was mild in most of these patients, while one of them experienced severe COVID-19. Interleukin-17 has been related to the hyperinflammatory state in COVID-19 and IL-17 inhibitors were presented as promising targets for the prevention of aberrant inflammation and acute respiratory distress in COVID-19. However, this hypothesis still remains to be proved. Further studies are warranted in order to test the benefits and risks of IL-inhibitors in SARS-CoV-2 infected individuals.
Benefits and adverse effects of hydroxychloroquine, methotrexate and colchicine: searching for repurposable drug candidates.
Rheumatology international. 2020;(11):1741-1751
Repurposing of antirheumatic drugs has garnered global attention. The aim of this article is to overview available evidence on the use of widely used antirheumatic drugs hydroxychloroquine, methotrexate and colchicine for additional indications. Hydroxychloroquine has endothelial stabilizing and anti-thrombotic effects. Its use has been explored as an adjunctive therapy in refractory thrombosis in antiphospholipid syndrome. It may also prevent recurrent pregnancy losses in the absence of antiphospholipid antibodies. Hydroxychloroquine favourably modulates atherogenic lipid and glycaemic profiles. Methotrexate has been tried for modulation of cardiovascular events in non-rheumatic clinical conditions, although a large clinical trial failed to demonstrate a benefit. Colchicine has been shown to successfully reduce the risk of recurrent cardiovascular events in a large multicentric trial. Potential antifibrotic effects of colchicine require further exploration. Hydroxychloroquine, methotrexate and colchicine are also being tried at different stages of the ongoing Coronavirus Disease 19 (COVID-19) pandemic for prophylaxis and treatment. While the use of these agents is being diversified, their adverse effects should be timely diagnosed and prevented. Hydroxychloroquine can cause retinopathy and rarely cardiac and auditory toxicity, retinopathy being dose and time dependent. Methotrexate can cause transaminitis, cytopenias and renal failure, particularly in acute overdoses. Colchicine can rarely cause myopathies, cardiomyopathy, cytopenias and transaminitis. Strong evidence is warranted to keep balance between benefits of repurposing these old antirheumatic drugs and risk of their adverse effects.