Hydroxychloroquine (All indications except Antiphospholipid Syndrom)

Congenital heart defects

R analysis
id Study   Lib. in paper Exposition period    Study type 
 Control type 
 
Tags OR 95%CI x1/n1 x0/n0 no cases no exposed ROB Ref.
S13683
R53176		 Huybrechts (Controls unexposed, sick), 2021 Cardiac malformations 1st trimester retrospective cohort (claims database) unexposed, sick Adjustment: Yes Indication HCQ: Rheumatic diseases as a whole (Systemic lupus erythematosus, Rheumatoid arthritis, Sjogren's syndrome...) 1.20 [0.62;2.32] 31/2,045   249/21,679 280 2,045
ref
S13651
R52964		 Cooper (controls exposed to TNF-I), 2014 Cardiac defects 1st trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No Indication HCQ: Rheumatic diseases as a whole (Systemic lupus erythematosus, Rheumatoid arthritis, Sjogren's syndrome...) 1.16 [0.13;10.57] C
excluded (control group) 		4/194   1/56 5 194
ref
S13652
R52994		 Cooper (controls unexposed, sick), 2014 Cardiac defects 1st trimester retrospective cohort (claims database) unexposed, sick Adjustment: No Indication HCQ: Rheumatic diseases as a whole (Systemic lupus erythematosus, Rheumatoid arthritis, Sjogren's syndrome...) 8.10 [0.43;151.51] C 4/194   0/171 4 194
ref
S13672
R53118		 Vroom (controls exposed to sulfasalazine), 2009 Heart malformations 1st trimester retrospective cohort (claims database) exposed to other treatment, sick Adjustment: No Indication HCQ: Any or not specified 1.75 [0.33;9.24] 2/26   6/132 8 26
ref
Total 3 studies 1.37 [0.75;2.49] 292 2,265
x1: number of endpoints among exposed, n1: number of exposed; x0: number of endpoints among non exposed, n0: number of non exposed; C: calculated odds ratio from numbers of events and effectives

Forest plot

StudyTE95% CIn casesn exposedweightROBABCDEF Huybrechts (Controls unexposed, sick), 2021Huybrechts, 2021 1 1.20[0.62; 2.32]2802,04583%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: unclearROB reporting: moderate Cooper (controls unexposed, sick), 2014Cooper, 2014 2 8.10[0.43; 151.51]41944%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: unclearROB mesure: criticalROB reporting: moderate Vroom (controls exposed to sulfasalazine), 2009Vroom, 2009 3 1.75[0.33; 9.24]82613%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: unclearROB reporting: moderate Total (3 studies) I2 = 0% 1.37[0.75; 2.49]2922,2650.520.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, sick; 2: controls unexposed, sick; 3: controls exposed to sulfasalazine;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.37[0.75; 2.49]2922,2650%NAHuybrechts (Controls unexposed, sick), 2021 Cooper (controls unexposed, sick), 2014 Vroom (controls exposed to sulfasalazine), 2009 3 case control studiescase control studies 0 Type of controls unexposed, sickunexposed, sick 1.79[0.39; 8.20]2842,23936%NAHuybrechts (Controls unexposed, sick), 2021 Cooper (controls unexposed, sick), 2014 2 exposed to other treatment, sickexposed to other treatment, sick 1.75[0.33; 9.26]826 -NAVroom (controls exposed to sulfasalazine), 2009 1 Tags Adjustment   - No  - No 2.54[0.60; 10.83]122200%NACooper (controls unexposed, sick), 2014 Vroom (controls exposed to sulfasalazine), 2009 2   - Yes  - Yes 1.20[0.62; 2.32]2802,045 -NAHuybrechts (Controls unexposed, sick), 2021 1 Indication HCQ   - Any or not specified  - Any or not specified 1.75[0.33; 9.26]826 -NAVroom (controls exposed to sulfasalazine), 2009 1   - Rheumatic diseases as a whole (Syst ...  - Rheumatic diseases as a whole (Systemic lupus erythematosus, Rheumatoid arthritis, Sjogren's syndrome...) 1.79[0.39; 8.20]2842,23936%NAHuybrechts (Controls unexposed, sick), 2021 Cooper (controls unexposed, sick), 2014 2 All studiesAll studies 1.37[0.75; 2.49]2922,2650%NAHuybrechts (Controls unexposed, sick), 2021 Cooper (controls unexposed, sick), 2014 Vroom (controls exposed to sulfasalazine), 2009 30.520.01.0

Publication bias and p-hacking diagnosis

funnel plot

Funnel plot not drawn. Less than 3 points.

Asymetry test p-value = NaN (by Egger's regression)

not enought points

p values plot

Funnel plot not drawn. Less than 3 points.

Sub-groups analysis using all included studies

excluded 13651

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed, sick controlsunexposed, sick controls 1.79[0.39; 8.20]2842,23936%NAHuybrechts (Controls unexposed, sick), 2021 Cooper (controls unexposed, sick), 2014 2 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.51[0.40; 5.70]132200%NACooper (controls exposed to TNF-I), 2014 Vroom (controls exposed to sulfasalazine), 2009 20.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Kaplan (All indications) (Cardiovascular malf ...Kaplan (All indications) (Cardiovascular malformations) 1.06[0.29; 3.86]0%-Wwhatever (meta-analysis)T1+at least 1st trimesterstudies TTT4 metaPregmetaPreg 1.37[0.75; 2.49]0%2,265----Huybrechts (Controls unexposed, sick), 2021 Cooper (controls unexposed, sick), 2014 Vroom (controls exposed to sulfasalazine), 2009 30.510.01.0