Efficacy And Safety Of Hydroxychloroquine For The Treatment Of Osteoarthritis A Systematic Review And Meta-Analysis Of Randomized Controlled Trials

Purpose: Conventional disease-modifying anti-rheumatic drugs have been trialed in osteoarthritis (OA). Hydroxychloroquine (HCQ), which has shown its effectiveness in rheumatoid arthritis, has been trialed for the treatment of OA; however, its efficacy and safety remain unclear. This systematic review and meta-analysis evaluated the efficacy and safety of HCQ for the treatment of OA. Methods: MEDLINE, EMBASE, and Cochrane Central were searched from inception through June 2020. Two reviewers independently screened for randomized controlled trials (RCTs) comparing HCQ with placebo or other active-comparators for the treatment of knee, hand, or hip OA, extracted data, and performed Cochrane risk of bias assessments. Results: Six RCTs, four in hand OA, two in knee OA, consisting of 842 patients (436 in HCQ arm, 406 in control arm) were included. RCTs were conducted between 2012-2020, one each at UK, Netherlands, Germany, Italy, Iran, and Egypt; follow-up period ranged 24-52 weeks. High-quality evidence showed no clinically important pain reduction with HCQ compared to placebo/active-control in hand OA (SMD: 0.14, 95% CI-0.20, 0.48). Effect on pain reduction in knee and hand OA was small and non-significant (SMD: -0.09, 95% CI-0.44, 0.25). High-quality evidence showed no improvement in dysfunction with HCQ compared to placebo in hand OA patients (SMD: 0.08, 95% CI-0.23, 0.40). Effect on dysfunction improvement in knee and hand OA was modest and statistically non-significant (SMD: -0.20, 95% CI-0.57, 0.18). No improvement in QoL was observed in hand OA. Conclusions: HCQ has no benefit in reducing pain and improving physical function in hand and knee OA patients. Off-label use of HCQ for patients with OA should be discouraged, considering no additional benefit.Tabled 1Characteristics of the HCQ studies in OA patientsAuthor, Year, Country, Trial Name, Trial Registration NumberPublication typeGroupSample size, nWomen, n (%)Age, yBMIaOA typeKL gradebFollow-upKey outcome measuresDetails of interventions and doseFundingRisk of BiasSaviola, 2012, Italy, NA, NAFull-textHCQ1413 (95)63.5 (7.41)NRHand OARadiographic criteriac12 moVAS Dreiser’s Score Synovitis assed using UI Morning stiffness Physician and Patient Global Assessment ESR, CRP, ALP¸ RF400 mg tablet daily for 30 days, 200 mg maintenance daily for 11 monthsNRHighCLO2123 (95)60.0 (7.13)300 mg i.v. in 250 cc. of physiological saline solution for 7 days, followed by 100 mg i.m. maintenance dose for 14 days/3 monthsJokar, 2013, Iran, NA, IRCT138709121479N1Full-textHCQ2121 (100)48.3 (11.14)25.6 (3.05)Knee OA2, 324 wkWOMAC200 mg tablets twice daily for 6 monthsUniversityLowPLB2322 (95)47.6 (8.54)25.4 (2.79)Placebo tablets of 200 mg twice daily for 6 monthsAbou-Raya, 2014, Egypt, NA, NAAbstractHCQ83NRNRNRKnee OA3, 436 wkVAS WOMAC function ADL400 mg dailyNRHighPLB83PlaceboKingsbury, 2018, United Kingdom, HERO, ISRCTN91859104/EudraCT 2011-004300-38Full-textHCQ12497 (78)62.8 (9.1)28.4 (5.4)Hand OAACR12 moNRS AUSCAN pain and function OAQoL SF-12 Kallman score200, 300 or 400 mg daily with dosage calculated according to ideal body weight for a maximum of 6.5mg/kgNon-profit organisationLowPLB124106 (85)62.5 (9.2)29.3 (6.2)PlaceboLee, 2018, Netherlands, FABIO, NCT01148043Full-textHCQ9886 (88)57.7 (8.2)NRHand OA1, 2, or 324 wkVAS AUSCAN AIMS2-SF400 mg dailyUniversityLowPLB9882 (84)58.3 (7.0)PlaceboKedor, 2020, Germany, OA-TREAT, ISRCTN46445413//EUDRA CT 2011-001689-16AbstractHCQ7568 (90.6)52.4 (8.1)NRHand OAACR52 wkHAQ AUSCAN pain and function Morning stiffness SF-36 ESR Modified Kallmann score200-400 mg dailyUniversityLowPLB7860 (76.9)50.2 (6.6)Matching PlaceboAbbreviations: ACR; American College of Rheumatology; ADL, activities of daily living; AIMS2-SF, Arthritis Impact Measurement Scale 2 short form; ALP, alkaline phosphatase; BMI, Body Mass Index; CLO, clodronate; CRP, C-Reactive Protein; ESR, Erythrocyte Sedimentation Rate; HAQ, Health Assessment Questionnaire; HCQ, hydroxychloroquine; KL grade, Kellgren and Lawrence classification grades of radiographic OA; mo, months; NA, Not Applicable; NR, Not Reported; NRS, Numerical Rating Scale; OAQOL, osteoarthritis quality of life scale; PLB, placebo; RF: rheumatoid factor; RoB, risk of bias; SF-12, 12-Item Short Form Survey; SF-36, 36-Item Short Form Survey; UI, ultrasound imaging; VAS, Visual Analog Scale; wk, weeks; WOMAC,Western Ontario and McMaster Universities Osteoarthritis Index. Data expressed as mean (SD) or otherwise specified. a Calculated as weight in kilograms divided by height in meters squared. b Criteria mention if not use KL criteria c Radiographic criteria: sharp marginal defects, central crumbling erosions, gull-wing or saw-tooth deformities Open table in a new tab Abbreviations: ACR; American College of Rheumatology; ADL, activities of daily living; AIMS2-SF, Arthritis Impact Measurement Scale 2 short form; ALP, alkaline phosphatase; BMI, Body Mass Index; CLO, clodronate; CRP, C-Reactive Protein; ESR, Erythrocyte Sedimentation Rate; HAQ, Health Assessment Questionnaire; HCQ, hydroxychloroquine; KL grade, Kellgren and Lawrence classification grades of radiographic OA; mo, months; NA, Not Applicable; NR, Not Reported; NRS, Numerical Rating Scale; OAQOL, osteoarthritis quality of life scale; PLB, placebo; RF: rheumatoid factor; RoB, risk of bias; SF-12, 12-Item Short Form Survey; SF-36, 36-Item Short Form Survey; UI, ultrasound imaging; VAS, Visual Analog Scale; wk, weeks; WOMAC,Western Ontario and McMaster Universities Osteoarthritis Index. Data expressed as mean (SD) or otherwise specified. a Calculated as weight in kilograms divided by height in meters squared. b Criteria mention if not use KL criteria c Radiographic criteria: sharp marginal defects, central crumbling erosions, gull-wing or saw-tooth deformities