key: cord-0771243-m6gzner6
authors: Trefond, Ludovic; Drumez, Elodie; Andre, Marc; Costedoat-Chalumeau, Nathalie; Seror, Raphaèle; Devaux, Mathilde; Dernis, Emmanuelle; Dieudonné, Yannick; Mahou, Soumaya El; Lanteri, Aurelia; Melki, Isabelle; Queyrel, Viviane; Roumier, Mathilde; Schmidt, Jean; Barnetche, Thomas; Thomas, Thierry; Cacoub, Patrice; Belot, Alexandre; Aumaitre, Olivier; Richez, Christophe; Hachulla, Eric
title: Impact of hydroxychloroquine used as DMARD on SARS CoV-2 tests and infection evolution in a population of 871 patients with inflammatory rheumatic and musculoskeletal diseases
date: 2021-05-26
journal: Joint Bone Spine
DOI: 10.1016/j.jbspin.2021.105226
sha: f20de49b169316f9a2ddb7fda9eff74c832be8c6
doc_id: 771243
cord_uid: m6gzner6

nan

J o u r n a l P r e -p r o o f 5 The in vitro efficacy of synthetic antimalarial agents against SARS coronavirus 2 (SARS-CoV-2) has been described (1, 2) , as well as a potential in vitro effect, especially on nasopharyngeal PCR (3) . The effect on SARS-CoV-2 infection of treatment with hydroxychloroquine (HCQ), used as a disease-modifying anti-rheumatic drug (DMARD) with long-term impregnation, is unknown. The objective of this study was to evaluate the impact of HCQ, used as DMARD, on the rate of positivity of the SARS-CoV-2 nasopharyngeal PCR, and on the clinical signs of infection with SARS-CoV-2, its severity and evolution in the French iRMD (inflammatory rheumatic and musculoskeletal diseases) -COVID-19 cohort.

We conducted a multicentre retrospective study between 13 April 2020 and 29 July 2020 based on the French iRMD-COVID-19 cohort (4) . From the cohort, we selected all subjects aged over 18 years and macthed subjects with ongoing HCQ treatment with patients without at the time of infection with SARS-CoV-2. Matching criteria were age (± 5 years), gender, comorbidities considered as associated with poor prognosis (at least one vs none), an immunosuppressive treatment, and use of nasopharyngeal PCR to diagnose COVID-19.

(Statistical analysis in Appendix A, supplementary data S1) [See the supplementary material associated with this article online].

We analysed 871 patients and finally matched 71 HCQ-treated patients with 191 controls.

( Table 1, Table 2 and Appendix A, supplementary data S2). The 71 HCQ-treated patients (94% women) had a mean age of 53 ± 16 years. The patients were receiving HCQ for systemic lupus (n=42), Sjögren's syndrome (n=6), other systemic iRMDs (n=9) or for chronic inflammatory rheumatism: rheumatoid arthritis (n=11), other (n=3).

We report a comparative study of COVID-19 patients receiving HCQ for an iRMD versus controls, derived from a population of 871 iRMD COVID-19 patients. We found no Page 6 of 11 J o u r n a l P r e -p r o o f 6 difference in terms of either clinical symptoms, severity or proportion of positive nasopharyngal PCR in patients on HCQ compared to matched controls. Matching criteria have been described as risk factors for COVID-19-related death (5) . The present findings are derived from observational retrospective analyses, which are subject to well-known limitations. No information was available on HCQ treatment duration, dose and blood concentration, useful for verifying adherence (6) . It should be noted, however, that HCQ has a long half-life (7) and its concentration would remain within a sufficient range over the course of COVID-19. The frequency of corticosteroids treatment was higher in the HCQ group and its influence is questionable.The percentage of positive nasopharyngeal PCR was not lower in the HCQ group. Our in vivo data do not support the described potential in vitro effect (1).

Numerous studies have used HCQ to treat or to prevent COVID-19, with no significant effect (8) (9) (10) . One could argue that the targeted blood concentration of HCQ would only be reached after several weeks (6), which could have blunted its effects. A strength of our study is that the chronic impregnation of HCQ probably eliminates this putative bias. 

Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro

In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an openlabel non-randomized clinical trial

Severity of COVID-19 and survival in patients with rheumatic and inflammatory diseases: data from the French RMD COVID-19 cohort of 694 patients

Factors associated with COVID-19-related death using OpenSAFELY

Determinants of hydroxychloroquine blood concentration variations in systemic lupus erythematosus

Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology

Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19 : A Randomized Trial

Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19

Hydroxychloroquine for the Prevention of Covid-19 -Searching for Evidence

Values are presented as frequency (percentage) unless otherwise indicated. 1 matched on age (± 5 yrs), gender, comorbidity (at least one vs. none), use of immunosuppressive drugs (at least one vs. none), and use of PCR test for COVID-19; 2 37 missing values (n=8 in HCQtreated patients). ND indicates not done for binary variables with frequency<5 in the matched sample

AI²D , autoimmune and autoinflammatory diseases; NSAIDs, Non-steroidal anti-inflammatory drugs

ASD, absolute standardised difference; SD, standard deviation Reference category

1 matched on age (± 5 yrs), gender, comorbidity (at least one vs. none), use of immunosuppressive drugs (at least one vs. none), and use of PCR test for COVID-19. 2 P-value for overall comparison. 3 calculated using multinomial or binary logistic regression models adjusted for matching factors

We thank the members of the scientific committee of the FAI 2 R /SFR/SNFMI/SOFREMIP/CRI/IMIDIATE consortium for their regular and extensive work and discussions: Eric Hachulla, Alexandre Belot, Hélène Maillard, Sophie Georgin-Lavialle and Christophe Richez for FAI 2 R; Thierry Thomas for the SFR; Jacques Pouchot and Patrice

The authors have no competing interests.

Supplementary data (data S1-S3) associated with this article can be found in the online version at …