Login Register Cart 0
Generic placeholder image

Current Reviews in Clinical and Experimental Pharmacology

Editor-in-Chief

ISSN (Print): 2772-4328
ISSN (Online): 2772-4336

Back
Journal Home About Journal Editorial Board Current Issue Volumes/Issues
Subscribe
Meta-Analysis

A Systematic Review and Meta-Analysis of the Safety of Hydroxychloroquine in a Randomized Controlled Trial and Observational Studies

Author(s): Mahanjit Konwar, Miteshkumar Maurya, Urmila M. Thatte, Nithya J. Gogtay and Debdipta Bose*

Volume 17, Issue 3, 2022

Published on: 26 July, 2021

Page: [216 - 235] Pages: 20

DOI: 10.2174/1574884716666210726104424

Price: $65

conference banner
Abstract

Introduction: Hydroxychloroquine (HCQ) has recently become the focus of attention in the current COVID-19 pandemic. With an increase in the off-label use of HCQ, concern for the safety of HCQ has been raised. We, therefore, performed this systematic review to analyze the safety data of HCQ against placebo and active treatment in various disease conditions.

Methods: We searched PubMed, Embase, and Cochrane for Randomized Controlled Trials (RCTs) and Observational Studies (OSs) that evaluated HCQ for the treatment of any disease other than COVID19 in adult patients up to May 2020. We assessed the quality of the included studies using Risk of Bias 2 (for RCTs) and Newcastle–Ottawa Scale (for OSs). Data were analyzed with randomeffect meta-analysis. Sensitivity and subgroup analyses were performed to identify heterogeneity.

Results: A total of 6641 studies were screened, and 49 studies (40 RCTs and 9 OSs) with a total sample size of 35044 patients were included. The use of HCQ was associated with higher risks of TDAEs as compared to placebo/no active treatment [RR 1.47, 95%CI 1.03-2.08]. When HCQ was compared with active treatments, the risks of AEs [RR 0.74, 95% CI 0.63-0.86] and TDAEs were less in the HCQ arm [RR 0.57, 95% CI 0.39-0.81]. The outcomes did not differ in the sensitivity analysis.

Conclusion: The results suggest that the use of HCQ was associated with a lower risk of AEs and TDAEs as compared to active treatment, whereas posing higher risk of TDAEs as compared to placebo.

Keywords: Adverse events, active treatments, placebo, randomised controlled trial, HCQ, rheumatoid arthritis.

« Previous Next »
[1]
Ben-Zvi I, Kivity S, Langevitz P, Shoenfeld Y. Hydroxychloroquine: from malaria to autoimmunity. Clin Rev Allergy Immunol 2012; 42(2): 145-53.
[http://dx.doi.org/10.1007/s12016-010-8243-x] [PMID: 21221847]
[2]
Hydroxychloroquine - drug bank. Drugbankca 2020. Available from: https://www.drugbank.ca/drugs/DB01611#reference-L8072
[3]
Model list of essential medicines. Appswhoint 2019. Available from: https://apps.who.int/iris/bitstream/handle/10665/325771/WHO-MVP-EMP-IAU-2019.06-eng.pdf
[4]
Savarino A, Boelaert JR, Cassone A, Majori G, Cauda R. Effects of chloroquine on viral infections: An old drug against today’s diseases? Lancet Infect Dis 2003; 3(11): 722-7.
[http://dx.doi.org/10.1016/S1473-3099(03)00806-5] [PMID: 14592603]
[5]
Rathi S, Ish P, Kalantri A, Kalantri S. Hydroxychloroquine prophylaxis for COVID-19 contacts in India. Lancet Infect Dis 2020; 20(10): 1118-9.
[http://dx.doi.org/10.1016/S1473-3099(20)30313-3] [PMID: 32311324]
[6]
Hydroxychloroquine sulfate tablets, USP. Accessdata Fda Gov 2020. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/009768Orig1s051lbl.pdf
[7]
Chatre C, Roubille F, Vernhet H, Jorgensen C, Pers Y-M. Cardiac complications attributed to chloroquine and hydroxychloroquine: A systematic review of the literature. Drug Saf 2018; 41(10): 919-31.
[http://dx.doi.org/10.1007/s40264-018-0689-4] [PMID: 29858838]
[8]
Updates L. Live updates: Fills and prices for unproven covid-19 treatments - GoodRx. The GoodRx Prescription Savings Blog 2020. Available from: https://www.goodrx.com/blog/covid-19-treatments-fill-increases-price-changes/
[9]
Ledsom A. ydroxychloroquine–number of prescriptions explodes in france. Forbes Available from: https://www.forbes.com/sites/alexledsom/2020/05/10/hydroxychloroquinenumber-of-prescriptions-explode-in-france/
[10]
Research C for DE and. FDA cautions against use of hydroxychloroquine or chloroquine for COVID-19 outside of the hospital setting or a clinical trial due to risk of heart rhythm problems. FDA 2020. Available from: https://www.fda.gov/drugs/drug-safety-and-availability/fda-cautions-against-use-hydroxychloroquine-or-chloroquine-covid-19-outside-hospital-setting-or
[11]
Hydroxychloroquine sulphate tablests, USP. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/009768s037s045s047lbl.pdf
[12]
Tang W, Cao Z, Han M, et al. Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial. BMJ 2020; 369: m1849.
[http://dx.doi.org/10.1136/bmj.m1849] [PMID: 32409561]
[13]
The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: Explanation and elaboration. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2714672/
[14]
Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 [last updated in 2017]. [pdf] Bethesda, Maryland, USA: National Cancer Institute, NIH, pp.1-146. Available at: https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcae_v5_quick_reference_5x7.pdf
[15]
Tietje C, Brouder A. 2009. Handbook of Transnational Economic Governance Regimes (Transnational Economic Governance Regimes). Sussex: Martinus Nijhoff Publishers, pp.1041- 1053.
[16]
Abraham J. RoB 2: A revised cochrane risk-of-bias tool for randomized trial. 2010. Available from: /bias/resources/rob-2-revisedcochrane- risk-bias-tool-randomized-trials
[17]
Wells GA, Shea B, O’Connell D, et al. Ottawa Hospital Research Institute. Available from: http://www.ohri.ca/programs/clinical_ epidemiology/oxford.asp
[18]
DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986; 7(3): 177-88.
[http://dx.doi.org/10.1016/0197-2456(86)90046-2] [PMID: 3802833]
[19]
Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003; 327(7414): 557-60.
[http://dx.doi.org/10.1136/bmj.327.7414.557] [PMID: 12958120]
[20]
Egger M, Davey SG, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315(7109): 629-34.
[http://dx.doi.org/10.1136/bmj.315.7109.629] [PMID: 9310563]
[21]
Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics 1994; 50(4): 1088-101.
[http://dx.doi.org/10.2307/2533446] [PMID: 7786990]
[22]
Duval S, Tweedie R. Trim and fill: A simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics 2000; 56(2): 455-63.
[http://dx.doi.org/10.1111/j.0006-341X.2000.00455.x] [PMID: 10877304]
[23]
Boonpiyathad T, Sangasapaviliya A. Hydroxychloroquine in the treatment of anti-histamine refractory chronic spontaneous urticaria, randomized single-blinded placebo-controlled trial and an open label comparison study. Eur Ann Allergy Clin Immunol 2017; 49(5): 220-4.
[http://dx.doi.org/10.23822/EurAnnACI.1764-1489.11] [PMID: 28884989]
[24]
Borg AA, Davis MJ, Fowler PD, Shadforth MF, Dawes PT. Rifampicin in early rheumatoid arthritis. Scand J Rheumatol 1993; 22(1): 39-42.
[http://dx.doi.org/10.3109/03009749309095110] [PMID: 8434246]
[25]
Clark P, Casas E, Tugwell P, et al. Hydroxychloroquine compared with placebo in rheumatoid arthritis. A randomized controlled trial. Ann Intern Med 1993; 119(11): 1067-71.
[http://dx.doi.org/10.7326/0003-4819-119-11-199312010-00002] [PMID: 8239224]
[26]
Das SK, Pareek A, Mathur DS, et al. Efficacy and safety of hydroxychloroquine sulphate in rheumatoid arthritis: A randomized, double-blind, placebo controlled clinical trial-an Indian experience. Curr Med Res Opin 2007; 23(9): 2227-34.
[http://dx.doi.org/10.1185/030079907X219634] [PMID: 17692155]
[27]
Davis MJ, Dawes PT, Fowler PD, Clarke S, Fisher J, Shadforth MF. Should disease-modifying agents be used in mild rheumatoid arthritis? Br J Rheumatol 1991; 30(6): 451-4.
[http://dx.doi.org/10.1093/rheumatology/30.6.451] [PMID: 1747702]
[28]
Desta M, Tadesse A, Gebre N, Barci BM, Torrey EF, Knable MB. Controlled trial of hydroxychloroquine in schizophrenia. J Clin Psychopharmacol 2002; 22(5): 507-10.
[http://dx.doi.org/10.1097/00004714-200210000-00011] [PMID: 12352275]
[29]
Erkan D, Unlu O, Sciascia S, et al. Hydroxychloroquine in the primary thrombosis prophylaxis of antiphospholipid antibody positive patients without systemic autoimmune disease. Lupus 2018; 27(3): 399-406.
[http://dx.doi.org/10.1177/0961203317724219] [PMID: 28764618]
[30]
Faarvang KL, Egsmose C, Kryger P, Pødenphant J, Ingeman-Nielsen M, Hansen TM. Hydroxychloroquine and sulphasalazine alone and in combination in rheumatoid arthritis: A randomised double blind trial. Ann Rheum Dis 1993; 52(10): 711-5.
[http://dx.doi.org/10.1136/ard.52.10.711] [PMID: 7903034]
[31]
Fong T, Trinkaus K, Adkins D, et al. A randomized double-blind trial of hydroxychloroquine for the prevention of chronic graft-versus-host disease after allogeneic peripheral blood stem cell transplantation. Biol Blood Marrow Transplant 2007; 13(10): 1201-6.
[http://dx.doi.org/10.1016/j.bbmt.2007.06.012] [PMID: 17889357]
[32]
Gerstein HC, Thorpe KE, Taylor DW, Haynes RB. The effectiveness of hydroxychloroquine in patients with type 2 diabetes mellitus who are refractory to sulfonylureas-a randomized trial. Diabetes Res Clin Pract 2002; 55(3): 209-19.
[http://dx.doi.org/10.1016/S0168-8227(01)00325-4] [PMID: 11850097]
[33]
Gottenberg J-E, Ravaud P, Puéchal X, et al. Effects of hydroxychloroquine on symptomatic improvement in primary Sjögren syndrome: the JOQUER randomized clinical trial. JAMA 2014; 312(3): 249-58.
[http://dx.doi.org/10.1001/jama.2014.7682] [PMID: 25027140]
[34]
Haar D, Sølvkjaer M, Unger B, Rasmussen K-JE, Christensen L, Hansen TM. A double-blind comparative study of hydroxychloroquine and dapsone, alone and in combination, in rheumatoid arthritis. Scand J Rheumatol 1993; 22(3): 113-8.
[http://dx.doi.org/10.3109/03009749309099254] [PMID: 8316771]
[35]
A randomized trial of hydroxychloroquine in early rheumatoid arthritis: the HERA Study. Am J Med 1995; 98(2): 156-68.
[http://dx.doi.org/10.1016/S0002-9343(99)80399-4] [PMID: 7847432]
[36]
Horne GA, Stobo J, Kelly C, Mukhopadhyay A, Latif AL, Dixon-Hughes J. A randomised phase II trial of hydroxychloroquine and imatinib versus imatinib alone for patients with chronic myeloid leukaemia in major cytogenetic response with residual disease. Leukemia 2020. Available from:http://www.nature.com/articles/s41375-019-0700-9
[37]
Hsia SH, Duran P, Lee ML, Davidson MB. Randomized controlled trial comparing hydroxychloroquine with pioglitazone as third-line agents in type 2 diabetic patients failing metformin plus a sulfonylurea: A pilot study. J Diabetes 2020; 12(1): 91-4.
[http://dx.doi.org/10.1111/1753-0407.12989] [PMID: 31574564]
[38]
Jessop JD, O’Sullivan MM, Lewis PA, et al. A long-term five-year randomized controlled trial of hydroxychloroquine, sodium aurothiomalate, auranofin and penicillamine in the treatment of patients with rheumatoid arthritis. Br J Rheumatol 1998; 37(9): 992-1002.
[http://dx.doi.org/10.1093/rheumatology/37.9.992] [PMID: 9783766]
[39]
Jokar M, Keyvanpajouh K. The effect of hydroxychloroquine on symptoms of knee osteoarthritis: A double-blind randomized controlled clinical trial. Iran J Med Sci 2013; 38(3): 6.
[40]
Karasic TB, O’Hara MH, Loaiza-Bonilla A, et al. Effect of gemcitabine and nab-paclitaxel with or without hydroxychloroquine on patients with advanced pancreatic cancer: A phase 2 randomized clinical trial. JAMA Oncol 2019; 5(7): 993-8.
[http://dx.doi.org/10.1001/jamaoncol.2019.0684] [PMID: 31120501]
[41]
Kingsbury SR, Tharmanathan P, Keding A, et al. Hydroxychloroquine effectiveness in reducing symptoms of hand osteoarthritis: A randomized trial. Ann Intern Med 2018; 168(6): 385-95.
[http://dx.doi.org/10.7326/M17-1430] [PMID: 29459986]
[42]
Kravvariti E, Koutsogianni A, Samoli E, Sfikakis PP, Tektonidou MG. The effect of hydroxychloroquine on thrombosis prevention and antiphospholipid antibody levels in primary antiphospholipid syndrome: A pilot open label randomized prospective study. Autoimmun Rev 2020; 19(4)102491
[http://dx.doi.org/10.1016/j.autrev.2020.102491] [PMID: 32084592]
[43]
Lajoie J, Birse K, Mwangi L, et al. Using safe, affordable and accessible non-steroidal anti-inflammatory drugs to reduce the number of HIV target cells in the blood and at the female genital tract. J Int AIDS Soc 2018; 21(7)e25150
[http://dx.doi.org/10.1002/jia2.25150] [PMID: 30047573]
[44]
Lee W, Ruijgrok L, Boxma-de Klerk B, et al. Efficacy of hydroxychloroquine in hand osteoarthritis: A randomized, double-blind, placebo-controlled trial. Arthritis Care Res (Hoboken) 2018; 70(9): 1320-5.
[http://dx.doi.org/10.1002/acr.23471] [PMID: 29125901]
[45]
Liu L-J, Yang YZ, Shi S-F, et al. Effects of hydroxychloroquine on proteinuria in Iga nephropathy: A randomized controlled trial. Am J Kidney Dis 2019; 74(1): 15-22.
[http://dx.doi.org/10.1053/j.ajkd.2019.01.026] [PMID: 30922594]
[46]
Le Loët X, Nordström D, Rodriguez M, et al. Effect of anakinra on functional status in patients with active rheumatoid arthritis receiving concomitant therapy with traditional disease modifying antirheumatic drugs: Evidence from the OMEGA trial. J Rheumatol 2008; 35(8): 1538-44.
[47]
Majzoobi MM, Hashemi SH, Mamani M, Keramat F, Poorolajal J, Ghasemi BHR. Effect of hydroxychloroquine on treatment and recurrence of acute brucellosis: A single-blind, randomized clinical trial. Int J Antimicrob Agents 2018; 51(3): 365-9.
[http://dx.doi.org/10.1016/j.ijantimicag.2017.08.009] [PMID: 28826825]
[48]
O’Dell JR, Leff R, Paulsen G, et al. Treatment of rheumatoid arthritis with methotrexate and hydroxychloroquine, methotrexate and sulfasalazine, or a combination of the three medications: results of a two-year, randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2002; 46(5): 1164-70.
[http://dx.doi.org/10.1002/art.10228] [PMID: 12115219]
[49]
O’Dell JR, Blakely KW, Mallek JA, et al. Treatment of early seropositive rheumatoid arthritis: A two-year, double-blind comparison of minocycline and hydroxychloroquine. Arthritis Rheum 2001; 44(10): 2235-41.
[http://dx.doi.org/10.1002/1529-0131(200110)44:10<2235:AID-ART385>3.0.CO;2-A] [PMID: 11665963]
[50]
Pareek A, Khopkar U, Sacchidanand S, Chandurkar N, Naik GS. Comparative study of efficacy and safety of hydroxychloroquine and chloroquine in polymorphic light eruption: A randomized, double-blind, multicentric study. Indian J Dermatol Venereol Leprol 2008; 74(1): 18-22.
[http://dx.doi.org/10.4103/0378-6323.38401] [PMID: 18187817]
[51]
Pareek A, Chandurkar N, Thomas N, et al. Efficacy and safety of hydroxychloroquine in the treatment of type 2 diabetes mellitus: A double blind, randomized comparison with pioglitazone. Curr Med Res Opin 2014; 30(7): 1257-66.
[http://dx.doi.org/10.1185/03007995.2014.909393] [PMID: 24669876]
[52]
Pareek A, Chandurkar N, Thulaseedharan NK, et al. Efficacy and safety of fixed dose combination of atorvastatin and hydroxychloroquine: A randomized, double-blind comparison with atorvastatin alone among Indian patients with dyslipidemia. Curr Med Res Opin 2015; 31(11): 2105-17.
[http://dx.doi.org/10.1185/03007995.2015.1087989] [PMID: 26371518]
[53]
Paton NI, Goodall RL, Dunn DT, et al. Effects of hydroxychloroquine on immune activation and disease progression among HIV-infected patients not receiving antiretroviral therapy: A randomized controlled trial. JAMA 2012; 308(4): 353-61.
[http://dx.doi.org/10.1001/jama.2012.6936] [PMID: 22820788]
[54]
Quatraro A, Consoli G, Magno M, et al. Hydroxychloroquine in decompensated, treatment-refractory noninsulin-dependent diabetes mellitus. A new job for an old drug? Ann Intern Med 1990; 112(9): 678-81.
[http://dx.doi.org/10.7326/0003-4819-112-9-678] [PMID: 2110430]
[55]
Ruzicka T, Sommerburg C, Goerz G, Kind P, Mensing H. Treatment of cutaneous lupus erythematosus with acitretin and hydroxychloroquine. Br J Dermatol 1992; 127(5): 513-8.
[http://dx.doi.org/10.1111/j.1365-2133.1992.tb14851.x] [PMID: 1467292]
[56]
Sarzi-Puttini P, D’Ingianna E, Fumagalli M, et al. An open, randomized comparison study of cyclosporine A, cyclosporine A + methotrexate and cyclosporine A + hydroxychloroquine in the treatment of early severe rheumatoid arthritis. Rheumatol Int 2005; 25(1): 15-22.
[http://dx.doi.org/10.1007/s00296-003-0384-2] [PMID: 14530867]
[57]
Sperber K, Chiang G, Chen H, et al. Comparison of hydroxychloroquine with zidovudine in asymptomatic patients infected with human immunodeficiency virus type 1. Clin Ther 1997; 19(5): 913-23.
[http://dx.doi.org/10.1016/S0149-2918(97)80045-8] [PMID: 9385480]
[58]
Van Gool WA, Weinstein HC, Scheltens P, Walstra GJ. Effect of hydroxychloroquine on progression of dementia in early Alzheimer’s disease: An 18-month randomised, double-blind, placebo-controlled study. Lancet 2001; 358(9280): 455-60.
[http://dx.doi.org/10.1016/S0140-6736(01)05623-9] [PMID: 11513909]
[59]
van Jaarsveld CHM, Jahangier ZN, Jacobs JWG, et al. Toxicity of anti-rheumatic drugs in a randomized clinical trial of early rheumatoid arthritis. Rheumatology (Oxford) 2000; 39(12): 1374-82.
[http://dx.doi.org/10.1093/rheumatology/39.12.1374] [PMID: 11136881]
[60]
Wasko MCM, McClure CK, Kelsey SF, Huber K, Orchard T, Toledo FGS. Antidiabetogenic effects of hydroxychloroquine on insulin sensitivity and beta cell function: A randomised trial. Diabetologia 2015; 58(10): 2336-43.
[http://dx.doi.org/10.1007/s00125-015-3689-2] [PMID: 26197707]
[61]
Yokogawa N, Eto H, Tanikawa A, et al. Effects of hydroxychloroquine in patients with cutaneous lupus erythematosus: A multicenter, double-blind, randomized, parallel-group trial. Arthritis Rheumatol 2017; 69(4): 791-9.
[http://dx.doi.org/10.1002/art.40018] [PMID: 27992698]
[62]
Yoon CH, Lee HJ, Lee EY, et al. Effect of hydroxychloroquine treatment on dry eyes in subjects with primary sjögren’s syndrome: A double-blind randomized control study. J Korean Med Sci 2016; 31(7): 1127-35.
[http://dx.doi.org/10.3346/jkms.2016.31.7.1127] [PMID: 27366013]
[63]
Desai RJ, Eddings W, Liao KP, Solomon DH, Kim SC. Disease-modifying antirheumatic drug use and the risk of incident hyperlipidemia in patients with early rheumatoid arthritis: A retrospective cohort study. Arthritis Care Res (Hoboken) 2015; 67(4): 457-66.
[http://dx.doi.org/10.1002/acr.22483] [PMID: 25302481]
[64]
Hanaoka H, Iida H, Kiyokawa T, Takakuwa Y, Kawahata K. Glucocorticoid, immunosuppressant, hydroxychloroquine monotherapy, or no therapy for maintenance treatment in systemic lupus erythematosus without major organ manifestations. Clin Rheumatol 2019; 38(10): 2785-91.
[http://dx.doi.org/10.1007/s10067-019-04633-y] [PMID: 31175481]
[65]
Hsu C-Y, Lin Y-S, Su Y-J, et al. Effect of long-term hydroxychloroquine on vascular events in patients with systemic lupus erythematosus: A database prospective cohort study. Rheumatology (Oxford) 2017; 56(12): 2212-21.
[http://dx.doi.org/10.1093/rheumatology/kex357] [PMID: 29029334]
[66]
Ju U-H, Liu F-C, Lin C-S, et al. Risk of Parkinson disease in Sjögren syndrome administered ineffective immunosuppressant therapies: A nationwide population-based study. Medicine (Baltimore) 2019; 98(14)e14984
[http://dx.doi.org/10.1097/MD.0000000000014984] [PMID: 30946325]
[67]
Alpay-Kanitez N, Pehlivan Ö, Omma A, et al. Favorable retention rates and safety of conventional anti-rheumatic drugs in older patients with rheumatoid arthritis. Medicine (Baltimore) 2020; 99(16)e19696
[http://dx.doi.org/10.1097/MD.0000000000019696] [PMID: 32311948]
[68]
Kumar A, Prakash AS. Effectiveness and safety of hydroxychloroquine compared to teneligliptin in uncontrolled T2DM patients as add-on Therapy. J ASEAN Fed Endocr Soc 2019; 34(1): 87-91.
[http://dx.doi.org/10.15605/jafes.034.01.13] [PMID: 33442141]
[69]
Sharma TS, Wasko MCM, Tang X, et al. Hydroxychloroquine use is associated with decreased incident cardiovascular events in rheumatoid arthritis patients. J Am Heart Assoc 2016; 5(1)e002867
[http://dx.doi.org/10.1161/JAHA.115.002867] [PMID: 26727968]
[70]
van Roeden SE, Bleeker-Rovers CP, de Regt MJA, et al. Treatment of chronic q fever: Clinical efficacy and toxicity of antibiotic regimens. Clin Infect Dis 2018; 66(5): 719-26.
[http://dx.doi.org/10.1093/cid/cix886] [PMID: 29040457]
[71]
Wu C-L, Chang C-C, Kor C-T, et al. Hydroxychloroquine use and risk of CKD in patients with rheumatoid arthritis. Clin J Am Soc Nephrol 2018; 13(5): 702-9.
[http://dx.doi.org/10.2215/CJN.11781017] [PMID: 29661770]
[72]
Shipman WD, Vernice NA, Demetres M, Jorizzo JL. An update on the use of hydroxychloroquine in cutaneous lupus erythematosus: A systematic review. J Am Acad Dermatol 2020; 82(3): 709-22.
[http://dx.doi.org/10.1016/j.jaad.2019.07.027] [PMID: 31306730]
[73]
Methotrexate 25 mg Tablets - Summary of Product Characteristics (SmPC) - (emc) Available from: https://www.medicines.org.uk/emc/product/511/smpc#UNDESIRABLE_EFFECTS

Rights & Permissions Print Cite
Article Metrics
25
1
© 2024 Bentham Science Publishers | Privacy Policy