Hydroxychloroquine (All indications except Antiphospholipid Syndrom) updated on 10-07-2022

Preeclampsia

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.
S13666
R53069		 Reynolds, 2022 Pre-eclampsia throughout pregnancy retrospective cohort unexposed, sick Adjustment: No Indication HCQ: Systemic lupus erythematosus (SLE) 1.02 [0.46;2.23] C 15/142   13/125 28 142
ref
S13670
R53110		 Tang, 2022 Preeclampsia or severe eclampsia (combination of hypertension, proteinuria and organ damage) during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No Indication HCQ: IgA nephropathy 0.30 [0.06;1.45] C 2/25   14/63 16 25
ref
S13769
R53863		 Canti, 2021 Preeclampsia throughout pregnancy prospective cohort unexposed, sick Adjustment: No Indication HCQ: Systemic lupus erythematosus (SLE) 0.14 [0.01;1.32] C 1/39   4/25 5 39
ref
S13696
R53281		 Haase, 2021 Preeclampsia during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: Yes Indication HCQ: Systemic lupus erythematosus (SLE) 0.47 [0.15;1.52] 9/82   16/108 25 82
ref
S13775
R53914		 Liu, 2021 Preeclampsia during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Indication HCQ: Systemic lupus erythematosus (SLE) Matched 0.83 [0.26;2.72] 6/40   7/40 13 40
ref
S13697
R53287		 Louthrenoo, 2021 Pregnancy induced hypertension during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No Indication HCQ: Systemic lupus erythematosus (SLE) 0.63 [0.09;3.50] 3/43   5/47 8 43
ref
S13707
R53362		 Abd Rahman, 2020 Preeclampsia during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: Yes Indication HCQ: Systemic lupus erythematosus (SLE) 0.08 [0.02;0.36] -/47   -/35 - 47
ref
S13773
R53883		 Baalbaki, 2020 Preeclampsia with severe features during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No Indication HCQ: Systemic lupus erythematosus (SLE) 0.78 [0.26;2.37] C 9/47   7/30 16 47
ref
S13654
R53029		 Do, 2020 Preeclampsia during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: Yes Indication HCQ: Systemic lupus erythematosus (SLE) 0.40 [0.20;1.30] 7/53   20/76 27 53
ref
S13694
R53245		 Kiatkongchuchai, 2020 Preeclampsia (NOS) during pregnancy (anytime or not specified) nested case control unexposed, sick Adjustment: No Indication HCQ: Systemic lupus erythematosus (SLE) 0.26 [0.02;0.69] -/-   0/- - -
ref
S13713
R53413		 Mollerach, 2019 Pre-eclampsia throughout pregnancy retrospective cohort unexposed, sick Adjustment: No Indication HCQ: Rheumatic diseases as a whole (Systemic lupus erythematosus, Rheumatoid arthritis, Sjogren's syndrome...) 3.00 [0.58;15.41] C 3/14   4/48 7 14
ref
S13715
R53420		 Seo, 2019 Preeclampsia throughout pregnancy retrospective cohort unexposed, sick Adjustment: Yes Indication HCQ: Systemic lupus erythematosus (SLE) 0.11 [0.02;0.67] 6/80   14/71 20 80
ref
S13699
R53328		 Kroese, 2017 Preeclampsia (hypertension (>140 mmHg systolic or >90 mmHg diastolic) combined with proteinuria) during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: Yes Indication HCQ: Systemic lupus erythematosus (SLE) 1.00 [1.00;1.00] 2/21   9/68 11 21
ref
S13687
R53210		 Leroux, 2015 Preeclampsia throughout pregnancy retrospective cohort unexposed, sick Adjustment: No Indication HCQ: Systemic lupus erythematosus (SLE) 1.14 [0.26;5.02] C 3/41   5/77 8 41
ref
S13702
R53354		 Chakravarty, 2005 Preeclampsia during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No Indication HCQ: Systemic lupus erythematosus (SLE) 1.20 [0.40;3.70] -/13   -/50 - 13
ref
S13661
R53058		 Levy, 2001 Toxemia 2nd and/or 3rd trimester randomized controlled trial unexposed, sick Adjustment: Randomisation Indication HCQ: Systemic lupus erythematosus (SLE) 0.10 [0.00;2.23] C 0/10   3/10 3 10
ref
S13701
R53350		 Buchanan, 1996 Preeclampsia during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No Indication HCQ: Systemic lupus erythematosus (SLE) 0.05 [0.01;0.39] C 1/34   20/53 21 34
ref
Total 16 studies 0.47 [0.28;0.77] 197 710
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 Reynolds, 2022Reynolds, 2022 1.02[0.46; 2.23]2814210%ROB confusion: criticalROB selection: unclearROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: moderate Tang, 2022Tang, 2022 0.30[0.06; 1.45]16256%ROB confusion: criticalROB selection: unclearROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Canti, 2021Canti, 2021 0.14[0.01; 1.32]5394%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Haase, 2021Haase, 2021 0.47[0.15; 1.52]25828%ROB confusion: seriousROB selection: unclearROB classification: unclearROB missing: unclearROB mesure: unclearROB reporting: moderate Liu, 2021Liu, 2021 0.83[0.26; 2.72]13408%ROB confusion: seriousROB selection: unclearROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Louthrenoo, 2021Louthrenoo, 2021 0.63[0.09; 3.50]8435%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Abd Rahman, 2020Abd Rahman, 2020 0.08[0.02; 0.36]-476%ROB confusion: criticalROB selection: criticalROB classification: unclearROB missing: unclearROB mesure: unclearROB reporting: moderate Baalbaki, 2020Baalbaki, 2020 0.78[0.26; 2.37]16478%ROB confusion: seriousROB selection: criticalROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Do, 2020Do, 2020 0.40[0.20; 1.30]27539%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Kiatkongchuchai, 2020Kiatkongchuchai, 2020 0.26[0.02; 0.69]--5%ROB confusion: criticalROB selection: unclearROB classification: unclearROB missing: unclearROB mesure: unclearROB reporting: moderate Mollerach, 2019Mollerach, 2019 3.00[0.58; 15.41]7146%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Seo, 2019Seo, 2019 0.11[0.02; 0.67]20805%ROB confusion: seriousROB selection: lowROB classification: unclearROB missing: unclearROB mesure: moderateROB reporting: moderate Leroux, 2015Leroux, 2015 1.14[0.26; 5.02]8416%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Chakravarty, 2005Chakravarty, 2005 1.20[0.40; 3.70]-138%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Levy, 2001Levy, 2001 0.10[0.00; 2.23]3102%ROB confusion: lowROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Buchanan, 1996Buchanan, 1996 0.05[0.01; 0.39]21344%ROB confusion: criticalROB selection: unclearROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Total (16 studies) I2 = 49% 0.47[0.28; 0.77]1977100.010.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 0.54[0.33; 0.88]17667645%NAReynolds, 2022 Tang, 2022 Canti, 2021 Haase, 2021 Liu, 2021 Louthrenoo, 2021 Abd Rahman, 2020 Baalbaki, 2020 Do, 2020 Mollerach, 2019 Seo, 2019 Leroux, 2015 Chakravarty, 2005 Levy, 2001 14 case control studiescase control studies 0.26[0.04; 1.53]-- -NAKiatkongchuchai, 2020 1 RCTRCT 0.05[0.01; 0.39]2134 -NABuchanan, 1996 1 Type of controls unexposed, sickunexposed, sick 0.47[0.28; 0.77]19771049%NAReynolds, 2022 Tang, 2022 Canti, 2021 Haase, 2021 Liu, 2021 Louthrenoo, 2021 Abd Rahman, 2020 Baalbaki, 2020 Do, 2020 Kiatkongchuchai, 2020 Mollerach, 2019 Seo, 2019 Leroux, 2015 Chakravarty, 2005 Levy, 2001 Buchanan, 1996 16 Tags Adjustment   - No  - No 0.71[0.41; 1.23]8333324%NAReynolds, 2022 Tang, 2022 Canti, 2021 Louthrenoo, 2021 Baalbaki, 2020 Kiatkongchuchai, 2020 Mollerach, 2019 Chakravarty, 2005 Levy, 2001 9   - Randomisation  - Randomisation 0.05[0.01; 0.39]2134 -NABuchanan, 1996 1   - Yes  - Yes 0.31[0.13; 0.73]8030352%NAHaase, 2021 Abd Rahman, 2020 Do, 2020 Seo, 2019 Leroux, 2015 5 Indication HCQ   - IgA nephropathy  - IgA nephropathy 0.30[0.06; 1.45]1625 -NATang, 2022 1   - Rheumatic diseases as a whole (Syst ...  - Rheumatic diseases as a whole (Systemic lupus erythematosus, Rheumatoid arthritis, Sjogren's syndrome...) 3.00[0.58; 15.41]714 -NAMollerach, 2019 1   - Systemic lupus erythematosus (SLE)  - Systemic lupus erythematosus (SLE) 0.43[0.26; 0.72]17467147%NAReynolds, 2022 Canti, 2021 Haase, 2021 Liu, 2021 Louthrenoo, 2021 Abd Rahman, 2020 Baalbaki, 2020 Do, 2020 Kiatkongchuchai, 2020 Seo, 2019 Leroux, 2015 Chakravarty, 2005 Levy, 2001 Buchanan, 1996 14 MatchedMatched 0.83[0.26; 2.72]1340 -NALiu, 2021 1 All studiesAll studies 0.47[0.28; 0.77]19771049%NAReynolds, 2022 Tang, 2022 Canti, 2021 Haase, 2021 Liu, 2021 Louthrenoo, 2021 Abd Rahman, 2020 Baalbaki, 2020 Do, 2020 Kiatkongchuchai, 2020 Mollerach, 2019 Seo, 2019 Leroux, 2015 Chakravarty, 2005 Levy, 2001 Buchanan, 1996 160.010.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.83.61.9140.000Reynolds, 2022Tang, 2022Canti, 2021Haase, 2021Liu, 2021Louthrenoo, 2021Abd Rahman, 2020Baalbaki, 2020Do, 2020Kiatkongchuchai, 2020Mollerach, 2019Seo, 2019Leroux, 2015Chakravarty, 2005Levy, 2001Buchanan, 1996

Asymetry test p-value = 0.0374 (by Egger's regression)

slope=0.8125 (0.6559); intercept=-2.2169 (0.9643); t=2.2989; p=0.0374

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed, sick controlsunexposed, sick controls Out of scale0.47[0.28; 0.77]19771049%NAReynolds, 2022 Tang, 2022 Canti, 2021 Haase, 2021 Liu, 2021 Louthrenoo, 2021 Abd Rahman, 2020 Baalbaki, 2020 Do, 2020 Kiatkongchuchai, 2020 Mollerach, 2019 Seo, 2019 Leroux, 2015 Chakravarty, 2005 Levy, 2001 Buchanan, 1996 160.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Clowse (All SLE (lupus) pregnancies) (Pre-ecl ...Clowse (All SLE (lupus) pregnancies) (Pre-eclampsia) 0.89[0.62; 1.29]NA-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT7 Naveau (SLE indication) (Pre-eclampsia)Naveau (SLE indication) (Pre-eclampsia) Out of scale0.49[0.59; 1.01]49%-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT-9 Duan (SLE indication) (Preeclampsia)Duan (SLE indication) (Preeclampsia) Out of scale0.35[0.21; 0.59]22%-U,Sunexposed, sickAllthroughout pregnancystudies TTT6 Liu (SLE indication) (Preeclampsia)Liu (SLE indication) (Preeclampsia) 0.61[0.34; 1.11]11%-U,Sunexposed, sickAnyduring pregnancy (anytime or not specified)studies TTT3 metaPregmetaPreg Out of scale0.47[0.28; 0.77]49%710----Reynolds, 2022 Tang, 2022 Canti, 2021 Haase, 2021 Liu, 2021 Louthrenoo, 2021 Abd Rahman, 2020 Baalbaki, 2020 Do, 2020 Kiatkongchuchai, 2020 Mollerach, 2019 Seo, 2019 Leroux, 2015 Chakravarty, 2005 Levy, 2001 Buchanan, 1996 160.510.01.0