To the Editor: Recent data suggested that about 50% of patients with cutaneous lupus erythematosus (CLE) reached remission after 5 years of treatment.1Florez-Pollack S. Rizvi S. Chong B. Hynan L. Factors associated with disease activity remission and recurrence in cutaneous lupus erythematosus [abstract].Arthritis Rheumatol. 2020; 72https://acrabstracts.org/abstract/factors-associated-with-disease-activity-remission-and-recurrence-in-cutaneous-lupus-erythematosusDate accessed: February 26, 2021Google Scholar However, to our knowledge, no study assessed the possibility of tapering the dose or discontinuing hydroxychloroquine (HCQ) after achieving remission in CLE. In this retrospective, multicenter cohort study, we enrolled biopsy-proven CLE patients2Kuhn A. Landmann A. The classification and diagnosis of cutaneous lupus erythematosus.J Autoimmun. 2014; 48-49: 14-19https://doi.org/10.1016/j.jaut.2014.01.021Crossref PubMed Scopus (135) Google Scholar who had HCQ dose tapering or discontinuation after reaching remission (the absence of erythema or scale/hyperkeratotic lesions). Patients were identified through electronic patient medical record between January 2000 and June 2020 and at least 6 months of follow-up after the first HCQ decrease. Patients who were receiving a treatment other than HCQ at the time of decrease were excluded. Kaplan-Meier survival curves were used to assess the risk of relapse, defined by the recurrence of cutaneous lesions or the appearance of new active cutaneous lesions reported by physicians and requiring modification of CLE treatment (including topical treatment). Two-tailed P < .05 was considered statistically significant. Fifty-six patients (48 women, 87%) were included. The characteristics of these patients are described in Table I. Eighteen patients (32%) had systemic lupus erythematosus (SLE), according to the Systemic Lupus International Collaborating Clinics criteria3Petri M. Orbai A.M. Alarcón G.S. et al.Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus.Arthritis Rheum. 2012; 64: 2677-2686https://doi.org/10.1002/art.34473Crossref PubMed Scopus (1) Google Scholar mostly articular. The dose of HCQ associated with remission in mg/kg of real body weight was 6.5 (range, 2.2-12 mg/kg) and 43 patients (76%) needed a dose higher than 5 mg/kg to obtain remission. Median HCQ intake duration before first dose reduction or discontinuation was 36 months (range, 3-500 months) and median follow-up duration was 5.9 years (range 0.7-21.3 years).Table IBaseline characteristics of patients with CLE who reduced or stopped hydroxychloroquine after complete cutaneous remission (n = 56)CLE featuresN (%)Demographic data Age at diagnosis, years (range)36 (11-81) Age at the time of HCQ reduction, y, median (range)46 (11-81) Female, n (%)48 (87) Obesity (BMI ≥ 30), n (%)2 (4) Fitzpatrick phototype V-VI, n (%)12 (21)Smoking status, n (%) Current smokers22 (39) Past smokers7 (13)CLE duration at the time of first HCQ reduction, years, median (range)3 (0.04-43)CLE subtypes, n (%) Acute CLE3 (5) Subacute CLE9 (16) Chronic CLEDLE31 (55)Chilblain lupus6 (11)Lupus panniculitis6 (11) Intermittent CLE: lupus erythematosus tumidus/dermal lupus19 (34)> 1 CLE subtypes, n (%)16 (29)CLE lesions location, n (%) Face42 (76) Scalp20 (36) Trunk/back20 (36) Upper or lower limb22 (40) Acral involvement15 (27)Immunologic and SLE features at baseline Positive antinuclear antibodies, n (%)38 (68) Positive anti-Ro/SSA antibodies, n (%)22 (40) Positive anti-dsDNA antibodies, n (%)14 (25)Systemic erythematosus lupus (≥4 SLICC 2012 criteria), n (%)18 (32)Systemic erythematosus lupus extracutaneous systemic features, n (%) Articular16 (28) Hematologic2 (3) Serositis1 (2) Libman-Sacks endocarditis1 (2) Hypocomplementemia vasculitis1 (2) Neurologic0 Renal0HCQ daily dose allowing complete remission, median (range) mg400 (200-800)HCQ daily dose allowing complete remission, median (range) in mg/kg of real body weight6.5 (range 2.2-12)Previous therapies,∗Previous treatments used to obtain remission. Patients were excluded if they received a treatment other than HCQ for CLE at the time of HCQ dose tapering or discontinuation, including topical treatment. n (%) Topical corticosteroids30 (54) Topical tacrolimus17 (30) Systemic corticosteroids14 (25) Thalidomide8 (14) Others†including: mycophenolate mofetil n = 1, lenalidomide n = 1.2 (4)Type of initial therapeutic strategy, N (%) Direct stop22 (39%)Relapse rate16 (73%) Continuous decrease19 (33%)Relapse rate9 (47%) Seasonal‡For seasonal strategy, hydroxychloroquine was stopped, or dose was reduced (from 400 to 200 mg/day) between October 1 and March 1. decrease and stop§Compared with other strategies, seasonal discontinuation was performed more frequently in patients who current smoker (P = .03).15 (27%)Relapse rate3 (20%)Treatment at relapse (among n = 34 patients with ≥ 1 relapse): No treatment26 (76%) HCQ decreased dose8 (24%)Dose of HCQ in mg/kg of real body weight3.2 (2.3-8.8)Season of relapse Winter2 (6%) Spring13 (38%) Summer6 (18%) Autumn13 (38%)BMI, Body mass index; CLE, cutaneous lupus erythematosus; DLE, discoid lupus erythematosus; HCQ, hydroxychloroquine.∗ Previous treatments used to obtain remission. Patients were excluded if they received a treatment other than HCQ for CLE at the time of HCQ dose tapering or discontinuation, including topical treatment.† including: mycophenolate mofetil n = 1, lenalidomide n = 1.‡ For seasonal strategy, hydroxychloroquine was stopped, or dose was reduced (from 400 to 200 mg/day) between October 1 and March 1.§ Compared with other strategies, seasonal discontinuation was performed more frequently in patients who current smoker (P = .03). Open table in a new tab BMI, Body mass index; CLE, cutaneous lupus erythematosus; DLE, discoid lupus erythematosus; HCQ, hydroxychloroquine. Thirty-four patients (61%) had at least 1 relapse during follow-up, with a median time to relapse of 3.6 years, including 26 (46%) patients after the first HCQ dose tapering or discontinuation and 8 (15%) after discontinuation secondary to sustained remission with seasonal or continuous dose reduction (Fig 1). During follow-up, 39 patients (70%) underwent HCQ complete discontinuation. Twenty-two patients (56%) relapsed after discontinuation during follow-up. Acral CLE was significantly associated with relapse (hazard ratio, 16.74; 95% CI, 3.38-84.82; P = .0006). SLE was not associated with cutaneous relapse (P = .98). However, in a cohort of 1460 SLE, flares or hospitalization for SLE occurred more frequently for HCQ discontinuation compared with a maintenance dose.4Almeida-Brasil C. Hanly J. Urowitz M. et al.Outcomes after hydroxychloroquine reduction or discontinuation in a multinational inception cohort of systemic lupus [abstract].Arthritis Rheumatol. 2020; 72https://acrabstracts.org/abstract/outcomes-after-hydroxychloroquine-reduction-or-discontinuation-in-a-multinational-inception-cohort-of-systemic-lupusDate accessed: February 27, 2021Google Scholar Therefore, we would not recommend stopping HCQ in SLE patients. All relapses were cutaneous only, except for 1 patient who had a systemic articular relapse. Median duration before relapse was not significantly different in patients with remission <1 year after HCQ initiation compared with >1 year (P = .47). At last follow-up, 23 patients (41%) were no longer receiving any oral treatment, 22 (39%) had a sustained decreased HCQ daily dose, and 11 (20%) restarted an active treatment. Long-term use of HCQ, as well a as dose greater than 5 mg/kg of real body weight5Melles R.B. Marmor M.F. The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy.JAMA Ophthalmol. 2014; 132: 1453-1460https://doi.org/10.1001/jamaophthalmol.2014.3459Crossref PubMed Scopus (355) Google Scholar delivered by a pharmacist are known to be associated with retinal toxicity. HCQ dose reduction might prevent retinopathy. In our study, no patient developed retinopathy during follow-up. This study is limited by its small sample size, retrospective design, missing data (in particular the absence of baseline Cutaneous Lupus Erythematosus Disease Area and Severity Index activity), and the heterogenous strategies that prevent identification of the optimal therapeutic scheme. The study suggests that reducing or stopping HCQ could be considered in CLE after remission, at least in a subset of patients, but this should be confirmed in a prospective study. None disclosed.