Response to: ‘Antirheumatic drugs, B cell depletion and critical COVID-19: correspondence on ‘Clinical course of coronavirus disease 2019 (COVID-19) in a series of 17 patients with systemic lupus erythematosus under long-term treatment with hydroxychloroquine by Mathian<i>et al</i>’ by Notz<i>et al</i>

Mathian, Alexis; Amoura, Zahir

doi:10.1136/annrheumdis-2020-218795

Cited by 36 publications

(32 citation statements)

References 16 publications

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“…If HCQ was effective against COVID‐19 at the doses used, it would be expected that patients with SLE receiving long‐term HCQ therapy (typically 200‐400 mg daily for years) will be relatively protected from COVID‐19 infection (pre‐exposure prophylaxis). Although it is almost impossible to compute this risk prospectively, available evidence shows that HCQ therapy at these doses does not confer protection to these patients 90‐93 …”

Section: Discussionmentioning

confidence: 99%

Chloroquine and hydroxychloroquine for COVID‐19: Perspectives on their failure in repurposing

Shah

2020

J Clin Pharm Ther

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What is known and Objective Non‐clinical studies suggest that chloroquine (CQ) and hydroxychloroquine (HCQ) have antiviral activities. Early clinical reports of successful HCQ‐associated reduction in viral load from small studies in COVID‐19 patients spurred a large number of national and international clinical trials to test their therapeutic potential. The objective of this review is to summarize the current evidence on the safety and efficacy of these two agents and to provide a perspective on why their repurposing has hitherto failed. Methods Published studies and rapidly emerging data were reviewed to gather evidence on safety and efficacy of CQ and HCQ in patients with COVID‐19 infection or as prophylaxis. The focus is on clinically relevant efficacy endpoints and their adverse effects on QT interval. Results and Discussion At the doses used, the two agents, given alone or with azithromycin (AZM), are not effective in COVID‐19 infection. The choice of (typically subtherapeutic) dosing regimens, influenced partly by "QT‐phobia," varied widely and seems anecdotal without any pharmacologically reliable supporting clinical evidence. A substantial proportion of patients receiving CQ/HCQ/AZM regimen developed QTc interval prolongation, many with absolute QTc interval exceeding the potential proarrhythmic threshold, but very few developed proarrhythmia. What is new and Conclusion The strategy to repurpose CQ/HCQ to combat COVID‐19 infection is overshadowed by concerns about their QT liability, resulting in choice of potentially subtherapeutic doses. Although the risk of QT‐related proarrhythmia is real, it is low and manageable by careful monitoring. Recent discontinuation of HCQ from at least four large studies effectively marks the end of efforts at repurposing of CQ or HCQ for COVID‐19 infection. This episode leaves behind important questions on dose selection and risk/benefit balance in repurposing drugs generally.

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Section: Discussionmentioning

confidence: 99%

Chloroquine and hydroxychloroquine for COVID‐19: Perspectives on their failure in repurposing

Shah

2020

J Clin Pharm Ther

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“…A case report by Showers et al [14] on a woman suffering from COVID-19 and concomitant complement-mediated coagulopathy and transient antiphospholipid antibody positivity points, along with other recent observations [15, 16], towards a possible link between COVID-19 and the generation of such antibodies with subsequent thromboembolic events. Importantly, this may explain the fact that despite adequate thromboprophylaxis, COVID-19 is still associated with a high rate of venous and arterial thromboembolic events.…”

mentioning

confidence: 87%

Investigations of Pathologists as a Key to Understanding Coronavirus Disease 2019

Menter

Tzankov

2020

Pathobiology

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“…5 While some studies suggest that underlying immunosuppressed state may be beneficial in that the subject does not mount an intense immune response resulting in less severe manifestations of the disease, 6,7 while others have reported a similar incidence if not more in patients with immunosuppressed state compared with patients without immunosuppression. 8,9 Covid-19 Global rheumatology alliance reported one of the largest series of 600 Covid-19 patients with various underlying rheumatological disorders from 40 countries. 10 Although the study did not report on the incidence of Covid-19 in these patients, a glucocorticoid dose of ≥10 mg/day was associated with higher odds of hospitalisation.…”

Section: Introductionmentioning

confidence: 99%

Impact of the COVID-19 pandemic on patients with systemic lupus erythematosus: Observations from an Indian inception cohort

Rathi

Singh

et al. 2020

Lupus

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Introduction The ongoing pandemic of COVID-19 has led to severe disruption of healthcare services worldwide. We conducted this study to assess the impact of COVID-19 pandemic on the management of Systemic Lupus Erythematosus (SLE) patients who were enrolled in the nation-wide inception cohort. Methods A questionnaire was administered to the SLE patients enrolled in the inception cohort. Questions related to the effect on disease activity, preventive measures adopted against COVID-19, the incidence of COVID-19, hardships faced in getting access to health care professionals and availability of medicines, adherence, fear of COVID-19 and the potential benefits of being part of the registry. Results A total of 1040 (90% females) patients completed the questionnaire. The mean age was 27.5 ± 19.1 years and the mean disease duration was 1.25 years. Twenty-Four (2.3%) patients had developed fever (>1 day) during this period, including one patient with additional symptoms of diarrhoea and anosmia, however, none of the patients developed COVID-19 infection. 262 patients (25.2%) reported financial difficulty during this period and patients reported an average excess expenditure of at least 2255.45 INR ($30) per month. 378 patients (36%) reported problems in getting their prescribed medicines due to lockdown. Of these, 167 (40%) patients needed to change their medication schedule due to this non-availability. Almost 54% of patients missed their scheduled follow up visits during the lockdown period and 37% of patients were unable to get their investigations done due to closure of laboratories and hospitals. 266 patients (25.5%) reported worsening of various symptoms of SLE during this period. Almost 61% patients felt confident that being associated with the inception cohort had helped them in managing their disease better during this period of lockdown as they received help in the form of timely and frequent telephonic consults, assistance in making the medicines available, and regular counselling resulting in abetment of their fears and anxieties. Conclusion The current COVID-19 pandemic has made a huge impact on our SLE patients. Patients faced difficulty in the availability of medicines, missed the doses of medicines, had financial constraints, and spent more money on health during the pandemic.

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Response to: ‘Antirheumatic drugs, B cell depletion and critical COVID-19: correspondence on ‘Clinical course of coronavirus disease 2019 (COVID-19) in a series of 17 patients with systemic lupus erythematosus under long-term treatment with hydroxychloroquine by Mathianet al’ by Notzet al

Cited by 36 publications

References 16 publications

Chloroquine and hydroxychloroquine for COVID‐19: Perspectives on their failure in repurposing

Chloroquine and hydroxychloroquine for COVID‐19: Perspectives on their failure in repurposing

Investigations of Pathologists as a Key to Understanding Coronavirus Disease 2019

Impact of the COVID-19 pandemic on patients with systemic lupus erythematosus: Observations from an Indian inception cohort

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