Hydroxychloroquine ineffective for COVID-19 prophylaxis in lupus and rheumatoid arthritis
Singer et al.
, Hydroxychloroquine ineffective for COVID-19 prophylaxis in lupus and rheumatoid arthritis
, Annals of the Rheumatic Diseases, doi:10.1136/annrheumdis-2020-218500
Comparison of the percentage of SLE/RA patients on immunosuppressants that were taking HCQ, for COVID-19 diagnosis versus other infections or outpatient visits, finding a similar percentage in each case.
No mortality of severity information is provided to determine if HCQ treated patients fared better. No adjustment for concomitant medications or severity.
This study is excluded in the after exclusion results of meta
not fully adjusting for the baseline risk differences within systemic autoimmune patients.
risk of case, 9.0% higher, RR 1.09, p = 0.62, treatment 55 of 10,700 (0.5%), control 104 of 22,058 (0.5%).
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Singer et al., 5 Aug 2020, retrospective, database analysis, USA, peer-reviewed, 3 authors.
Abstract: Hydroxychloroquine ineffective for COVID-19
prophylaxis in lupus and rheumatoid arthritis
The viewpoint of Graef et al resonates more each day.1 In a
pandemic where the cries for certainty were met with a flow
of mixed early study results, they admonish festina lente (‘make
haste slowly’)! Since Graef, there have been many studies of
hydroxychloroquine (HCQ) for treating COVID-19. These
include a randomised controlled trial of 150 mild-to-moderate
patients and three large observational studies, all inpatient
studies that failed to show benefit of HCQ treatment for
COVID-19.2–5 Now a new inpatient study, with >80% administered HCQ within 24 hours, finds HCQ associated with substantial mortality reduction.6 Festina lente indeed! A look at HCQ as
prophylaxis, where its long half-life can be leveraged, may help.7
Bozzalla Cassione and colleagues described a northern Italian
cohort of 165 patients with systemic lupus erythematosus
(SLE).8 HCQ users had 50% greater risk of COVID-19 (7.9%
vs 5.3%; 95% CI for the difference −9.9% to 9.7%), but were
limited by just 12 patients with COVID-19 and possible bias due
to concomitant immunosuppressive therapy. A Belgian study
of 225 patients with SLE found 7.9% of HCQ users and 8.2%
of non-HCQ users had COVID-19 (95% CI for the difference
−6.7% to 9.5%), and another Italian study of 914 rheumatologic patients found no preventive benefit for HCQ (0.89% vs
0.62%; 95% CI for the difference −0.84% to 4.28%).9 10 These
studies also had few cases (18 and 6) and possible confounding
of immunosuppressive therapy. These three studies convincingly prove that HCQ users get COVID-19. However, they all
lacked the sample size for meaningful CIs and could not rule out
a strong preventive effect for HCQ. We employed a different
methodology that accesses a larger population and expands
the cohort to include both patients with SLE and rheumatoid arthritis (RA). This substantially increased the sample size
despite only including patients on immunosuppressive therapy
to minimise patient heterogeneity in sequestering behaviour and
prioritisation for virus testing. If HCQ is effective prophylaxis,
then the proportion of patients with SLE/RA on immunosuppressants using HCQ should be less for COVID-19 cases than
for the general population.
We queried the commonly used TriNetX Research Network,
a federated health research network that aggregates electronic
health records from 36 US healthcare organisations (HCOs).
Queries return population counts ≥10 patients. We included
patients ≥18 years old with SLE or RA and a prescription for
an immunosuppressant, diagnosed with COVID-19 since 20
January 2020. An outpatient encounter during the prior year
was required to increase sensitivity of diagnoses and prescriptions. We then determined the proportion prescribed HCQ in
the prior year. SLE/RA diagnoses and prescriptions were within
the year preceding index diagnosis. With 90-day prescriptions
and three refills common, many patients get one prescription
per year, so only one prescription was required for HCQ or
We considered two control groups for the year prior to the
COVID-19 study period1: patients diagnosed with influenza/
pneumonia/other lower respiratory infection (I/P/LRI), as a
group with similar symptoms, and2 everyone with an outpatient
visit (OP). Diagnoses were based on ICD-10 codes and prescriptions were identified using the Veterans Affairs Drug Classification System. Data were accessed..
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