Discontinuation Of Hydroxychloroquine Research Articles

A case series of hydroxychloroquine exacerbating the dermatomyositis rash.

Hydroxychloroquine (HCQ) is an antimalarial agent that is commonly used in the management of rheumatic skin disease. Few reports exist documenting exacerbation of dermatomyositis (DM) related to HCQ. Herein, we describe three adult patients with worsening DM cutaneous disease after starting HCQ and resolution or improvement with cessation. The time to exacerbation ranged from two weeks to nine months after the initiation of HCQ 400mg/day. Two of the three patients had antibodies to transcription intermediary factor 1γ (TIF1γ) and the other had antibodies to anti-nuclear matrix protein 2 (NXP2). After discontinuation of HCQ, the time to improvement or resolution of cutaneous symptoms ranged from six weeks to six months. Hydroxychloroquine may be associated with worsening cutaneous features in DM. In patients who are not improving despite escalation of immunosuppressive medications, or are worsening, we recommend a trial of discontinuing HCQ.

Subacute cutaneous lupus erythematosus as a rare complication of disease-modifying therapy administration in multiple sclerosis: case report

BackgroundTeriflunomide, the active metabolite of leflunomide, is a disease-modifying therapy drug used for the treatment of multiple sclerosis (MS), yet the complications associated with this drug remain not fully understood. Here we present the rare case of a 28-year-old female MS patient who developed subacute cutaneous lupus erythematosus (SCLE) following teriflunomide treatment. Though SCLE has been reported to be associated with leflunomide, the current report represents the first documented evidence demonstrating SCLE as a potential teriflunomide treatment-related complication. Additionally, a literature review on the leflunomide-induced SCLE was conducted to emphasize the association of SCLE with teriflunomide, specifically amongst the female demographic with a preexisting autoimmune diathesis.Case presentationA 28-year-old female first presented with MS symptoms in the left upper limb along with blurred vision in the left eye. Medical and family histories were unremarkable. The patient exhibited positive serum biomarkers including ANA, Ro/SSA, La/SSB, and Ro-52 antibodies. Relapsing–remitting MS was diagnosed according to the 2017 McDonald’s diagnostic criteria, and remission was achieved upon intravenous administration of methylprednisolone followed by teriflunomide sequential therapy. Three months post-teriflunomide treatment, the patient developed multiple facial cutaneous lesions. SCLE was subsequently diagnosed and was attributed to treatment-related complication. Interventions include oral administration of hydroxychloroquine and tofacitinib citrate effectively resolved cutaneous lesions. Discontinuation of hydroxychloroquine and tofacitinib citrate treatment led to recurring SCLE symptoms under continuous teriflunomide treatment. Full remission of facial annular plaques was achieved after re-treatment with hydroxychloroquine and tofacitinib citrate. The patient’s clinical condition remained stable in long-term outpatient follow-ups.ConclusionsAs teriflunomide has become a standard disease-modifying therapy for MS, the current case report highlights the importance of monitoring treatment-related complications, specifically in relation to SCLE symptoms.

Clinical features of acute generalized exanthematous pustulosis caused by hydroxychloroquine in rheumatology patients and exploration of CARD14 gene mutations.

Acute generalized exanthematous pustulosis (AGEP) is a rare condition characterized by superficial pustules following drug ingestion or infection. Currently, there is no clear link between rheumatism and AGEP. It has been described that hydroxychloroquine (HCQ) is a rare cause of acute generalized epidermal necrolysis (AGEP). Presently, there are limited studies on HCQ-induced AGEP. We aimed to explore the clinical features and associated gene expression of AGEP induced after HCQ treatment exposure in rheumatology patients. We assessed patients with HCQ-induced AGEP diagnosed at the Second Affiliated Hospital of Guizhou University of Chinese Medicine between January 1, 2017, and May 1, 2022. We also reviewed similar cases reported in specific databases. The study included five females (mean age, 40.2 years), and the mean time from initiation of HCQ treatment to symptom onset was 12.2 d. All patients received steroids and allergy medications after HCQ discontinuation, and the rash completely resolved within an average of 25.2 d. We performed whole exome sequencing and Sanger validation in our patient sample. CARD14 gene mutations were detected in three patients. Additionally, seven mutation sites were detected. HCQ-induced AGEP may have a longer latency period and regression time than AGEP induced by other drugs. Our patients all experienced CARD14 gene mutations. AGEP often resolves with topical therapy and drug discontinuation, although some cases require systemic steroid therapy. In the future, patients with rheumatism should pay attention to the effectiveness of HCQ during treatment and be aware of the associated skin toxicity.

Prevalence and Risk Factors of Hydroxychloroquine Retinopathy in Rheumatic Patients with Dry Eye Symptoms

Purpose: Hydroxychloroquine is widely used for long-term treatment of rheumatic diseases, but the drug can trigger irreversible toxic retinopathy. We studied the prevalence of, and the risk factors for, hydroxychloroquine retinopathy in rheumatic patients with dry eye symptoms and we introduce a representative case.Methods: We retrospectively studied a cohort of 133 rheumatological patients who had taken hydroxychloroquine for at least 12 months and who visited our ophthalmology clinic with dry eye symptoms from April 2016 to December 2021. Hydroxychloroquine retinopathy was diagnosed via fundus photography, spectral-domain optical coherence tomography, the Humphrey visual field test, autofluorescence fundus photography, and multifocal electroretinography. The principal outcomes were the prevalence of retinopathy at the first screening and the risk factors.Results: Of the 133 patients, hydroxychloroquine retinopathy was diagnosed in seven (5.2%) at the first screenings. The Mann-Whitney U-test revealed that older age; higher daily doses; longer dosing duration; greater cumulative doses; and higher daily and cumulative doses/kg were statistically significant in terms of retinopathy development. On multivariate logistic regression analysis, the average daily dose (odds ratio [OR] 6.02; 95% confidence interval [CI] 1.64-22.12, 100 mg increments) and duration of dosing (OR 3.39; 95% CI 1.19-9.62, 5 years increments) remained statistically significant (P = 0.021, P = 0.007 respectively)Conclusions: Ophthalmologists should enquire about any history of hydroxychloroquine therapy, and perform a retinal examination, when encountering dry eye in patients with rheumatic disease. Early detection of hydroxychloroquine retinopathy followed by discontinuation of hydroxychloroquine is the only way to prevent visual loss. High daily drug doses and long dosing durations are risk factors for retinopathy.

Hydroxychloroquine Blood Concentrations Can Be Clinically Relevant Also After Drug Discontinuation.

Background and ObjectiveHydroxychloroquine was widely used during the severe acute respiratory syndrome coronavirus 2 pandemic as an antiviral drug. Most previous pharmacokinetic/pharmacodynamic studies on hydroxychloroquine were conducted on healthy volunteers or patients receiving long-term therapy. There are no studies on the elimination of hydroxychloroquine after short-term treatments. Hydroxychloroquine is known to have a pro-arrhythmic effect through QT interval prolongation, but data in this setting are not conclusive. Our aims were to estimate the time needed for hydroxychloroquine concentrations (CHCQ) to drop to a safe concentration (500 ng/mL) after a short-term therapeutic cycle and to correlate the corrected QT interval with CHCQ.MethodsWe collected blood samples and electrocardiograms of patients who underwent short-term therapy with hydroxychloroquine during drug intake and after discontinuation. Hydroxychloroquine concentrations were determined by high-performance liquid chromatography–tandem mass spectrometry and analysed with a linear regression model to estimate the elimination time of the drug after its discontinuation. We conducted a multivariate analysis of the corrected QT interval correlation with CHCQ.ResultsOur data suggest that short-term hydroxychloroquine courses can generate significant CHCQ persisting above 500 ng/mL up to 16 days after discontinuation of treatment. Corrected QT interval prolongation significantly correlates with CHCQ.ConclusionsThe study confirms the long half-life of hydroxychloroquine and its effect on the corrected QT interval even after short-term courses of the drug. This can inform the clinician using hydroxychloroquine treatments that it would be safer to start or re-initiate treatments with corrected QT interval-prolonging potential 16 days after hydroxychloroquine discontinuation.

Hydroxychloroquine pre-exposure prophylaxis for COVID-19 among healthcare workers: Initial experience from India.

Background:Hydroxychloroquine (HCQ) had generated considerable interest for coronavirus disease 2019 (COVID-19) prophylaxis. We conducted a prospective observational study at a tertiary care hospital in India, with dedicated COVID-19 care facilities.Objectives:Primary objective was incidence of adverse effects, secondary objective being efficacy in preventing COVID-19.Methods:Healthcare workers were recruited and grouped based on voluntary HCQ prophylaxis as per national guidelines. Side effects in HCQ group were graded in accordance with national cancer institute-common terminology criteria for adverse events (NCI-CTCAE) version 5.0. At 3–7-week follow-up, groups were compared for COVID-19 exposure, symptoms development and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RT-PCR results.Results:Among 358 participants recruited, 216 (60.3%) were males and mean age was 31.2 ± 6.6 years. Chemoprophylaxis was initiated by 258 (72%) participants. After loading dose, 7 (2.7%) reported grade 2 and 1 (0.4%) grade 3 adverse effects. Discontinuation of HCQ due to side effects was reported in 11 (4.3%) participants. Electrocardiogram was done by 50 (19.4%) participants on HCQ; no abnormalities were noted. A total of 106 (41%) among those taking and 63 (63%) among those not taking HCQ were tested for SARS-CoV-2 due to influenza-like illness or significant exposure. Among all participants, 25 (6.9%, 95% confidence interval [CI] 4.3–9.6) developed COVID-19 during the study period. In the group taking HCQ, 10 (3.9%) tested positive compared to 15 (15%) in the group not taking HCQ (P < 0.001). Odds ratio with HCQ intake was 0.34 (95% CI 0.13–0.83, P = 0.01) and the number needed to treat was 12.Conclusion:HCQ is safe at the recommended dose for pre-exposure prophylaxis of COVID-19.

Flares after hydroxychloroquine reduction or discontinuation: results from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort

ObjectivesTo evaluate systemic lupus erythematosus (SLE) flares following hydroxychloroquine (HCQ) reduction or discontinuation versus HCQ maintenance.MethodsWe analysed prospective data from the Systemic Lupus International Collaborating Clinics (SLICC) cohort, enrolled from...

Evaluation of the prophylactic effect of hydroxychloroquine on people in close-contact with patients with COVID-19

IntroductionThe coronavirus disease 2019 (COVID-19) pandemic has caused significant mortality worldwide. The disease attacks the lung tissue and may lead to acute respiratory distress syndrome. An in vitro study showed that hydroxychloroquine (HCQ) has a prophylactic effect against COVID-19 due to its anti-inflammatory effects. The present study aimed to evaluate the prophylactic effect of HCQ on individuals in close contact with patients with COVID-19. MethodIn this quasi-trial study, we prescribed HCQ for 7 days to all people who had close contact with a patient with COVID-19. All contacts underwent a nasal swab in two steps, and those positive for COVID-19 were excluded from the study. After 14 days of follow-up, the clinical and laboratory manifestations of COVID-19 were evaluated. ResultsA total of 113 participants completed the study. The HCQ group comprised 51 (45.13%) contacts, and 62 (54.86%) contacts were allocated to the control group. According to the results of clinical examination and real-time polymerase chain reaction test, 8 (12.90%) contacts in the control group were reported to have contracted COVID-19. In the HCQ group, 7 (13.72%) contacts were confirmed to have contracted COVID-19. There was no relationship between HCQ use and age, sex, underlying disorders, and laboratory data (all p > 0.05). In terms of HCQ side effects, five participants experienced gastrointestinal and cutaneous side effects that subsided on discontinuation of HCQ. ConclusionThe current study showed that HCQ had no prophylactic effect with regard to COVID-19 prevention.

Hydroxychloroquine dose tapering or discontinuation in cutaneous lupus erythematosus after remission: A retrospective multicenter cohort study of 56 patients

Hydroxychloroquine dose tapering or discontinuation in cutaneous lupus erythematosus after remission: A retrospective multicenter cohort study of 56 patients

Ocular findings in Japanese patients with hydroxychloroquine retinopathy developing within 3 years of treatment

To describe the characteristics of Japanese patients with hydroxychloroquine (HCQ) retinopathy developing within 3years of treatment outset. Retrospective case series METHODS: Three patients with HCQ retinopathy developing within 3years of treatment outset have been identified in Japan since HCQ became available in 2015. Their medical charts, containing optical coherence tomography (OCT), fundus autofluorescence imaging, and visual field tests, were reviewed. The treatment durations and cumulative doses until onset were 29-36months and 182-326g, respectively. The first patient had possible pre-existing maculopathy, although the abnormalities were ambiguous. The second and third patients had impaired renal function. The patients did not complain of severe visual disturbance at diagnosis, but visual field loss and disruption of the outer retinal segments consisting of a parafoveal pattern in the first case and a pericentral pattern (localized, 8 or more degrees from the center of the fovea) in the second and third cases were clearly observed on OCT. Even after HCQ discontinuation, their retinopathy showed slight progression on the visual field tests and OCT images. A blood sample was obtained from 1 patient on the day after HCQ discontinuation, and the whole blood level of HCQ was measured using validated liquid chromatography-tandem mass spectrometry. The HCQ level 27h after the last dose was high, at 2240ng/mL (suggested threshold > 1733ng/mL). Ophthalmologic screening from the initiation of HCQ treatment detected 3 cases of HCQ retinopathy developing within 3years of treatment outset, including a patient with a high blood level of HCQ.

P.841QTc changes in the management of SARS-CoV-2 infection in patents schizophrenia spectrum disorders

Background: Hydroxychloroquine (HCQ) has been one of the most recommended treatment strategies since the Covid19 outbreak was announced. Although the efficiency of the HCQ is controversial, adverse effects such as QTc prolongation is still considered to be major concern due to causing potential life-threatening cardiac rhythm problem. More specifically, concurrent use of HCQ with antipsychotics which known to be a potential risk factor for QTc prolongation another important issue that needs to be addressed. The aim of the present study is to explore the potential QTc prolongation side effect of HCQ when used concurrently with antipsychotics in patients diagnosed with schizophrenia spectrum disorders and covid19 infection. Method(s): We conducted a retrospective file analysis study in patients followed up inpatient psychiatric unit for Covid19 schizophrenia patients. 25 schizophrenia patients with covid19 infection electrocardiographic data were analyzed retrospectively during the follow-up period. Before initiation of the HCQ treatment, during and after the HCQ treatment, all the electrocardiographic data were analyzed a daily basis. Electrocardiographic measurements were made on the day before HCQ treatment, during the 5-day treatment period and for 7 days after treatment cessation. QTc intervals of 470 ms (females) and 450 ms (males) were considered borderline, longer QTc intervals were considered pathological. More than 500 ms prolongation in the QTc interval was considered to be a life-threatening situation. The current antipsychotic dose was applied by 50% less to prevent Qtc prolongation before the start of COVID 19 treatment, during the 5-day treatment period and for 7 days following treatment discontinuation. Result(s): According to the data analysis, QTc intervals were found to be exceeding the borderline limit between the day of 3rd and 5th of the HCQ treatment and on the first day of HCQ discontinuation compare to before HCQ (p values< 0.05). Since the borderline limits of prolongation in the QT interval are different in men and women, these two groups were evaluated separately at the next stage. While the borderline limit is 470 millisecond for women and 450 milliseconds for men, HCQ treatment just showed a significant difference on the day of the 2nd and 3rd days of the treatment period compared to before HCQ (p values<0.05). Accordingly, the difference in the QT duration according to the initial values reaches statistical significance only in women and on the 2nd and 3rd days of HCQ treatment (p values <0.05). When the data is analyzed individually, it is observed that the cases that exceed the borderline from time to time do not have a common feature in terms of drug use, clinical diagnosis, and concomitant disease, and these patients do not have any clinical signs and symptoms. Conclusion(s): In conclusion, HCQ is considered to be an effective treatment for Covid19 especially the early phase of the illness. Regarding the potential QTc prolongation, HCQ has become a potential risk factor for ventricular fibrillation and death. As a result, it was concluded that during HCQ treatment applied in Covid19 treatment, QTc prolongation may occur, antipsychotics may worsen this side effect, and dose adjustment is required [1-5]. No conflict of interestCopyright © 2020

Frequency of Long QT in Patients with SARS-CoV-2 Infection Treated with Hydroxychloroquine: A Meta-analysis

Introduction Hydroxychloroquine (HCQ) has been proposed as a SARS-CoV-2 treatment but the frequency of long QT (LQT) during use is unknown.Objective To conduct a meta-analysis of the frequency of LQT in patients with SARS-CoV-2 infection treated with HCQ.Data Sources PubMed, EMBASE, Google Scholar, the Cochrane Database of Systematic Reviews and preprint servers (medRxiv, Research Square) were searched for studies published between December 2019 and June 30, 2020.Methods Effect statistics were pooled using random effects. The quality of observational studies and randomized controlled trials was appraised with STROBE and the Cochrane Risk of Bias Assessment tools, respectively.Outcomes Critical LQT was defined as: (1) maximum QT corrected (QTc)≥500 ms (if QRS<120 ms) or QTc≥550 ms (if QRS≥120 ms), and (2) QTc increase ≥60 ms.Results In the 28 studies included (n=9124), the frequency of LQT during HCQ treatment was 6.7% (95% confidence interval [CI]: 3.7-10.2). In 20 studies (n=7825), patients were also taking other QT-prolonging drugs. The frequency of LQT in the other 8 studies (n=1299) was 1.7% (95% CI: 0.3-3.9). Twenty studies (n=6869) reported HCQ discontinuation due to LQT, with a frequency of 3.7% (95% CI: 1.5-6.6). The frequency of ventricular arrhythmias during HCQ treatment was 1.68% (127/7539) and that of arrhythmogenic death was 0.69% (39/5648). Torsades de Pointes occurred in 0.06% (3/5066). Patients aged >60 years were at highest risk of HCQ-associated LQT (P<0.001).Conclusions HCQ-associated cardiotoxicity in SARS-CoV-2 patients is uncommon but requires ECG monitoring, particularly in those aged >60 years and/or taking other QT-prolonging drugs.

Chloroquine and hydroxychloroquine for COVID-19: Perspectives on their failure in repurposing.

What is known and ObjectiveNon‐clinical studies suggest that chloroquine (CQ) and hydroxychloroquine (HCQ) have antiviral activities. Early clinical reports of successful HCQ‐associated reduction in viral load from small studies in COVID‐19 patients spurred a large number of national and international clinical trials to test their therapeutic potential. The objective of this review is to summarize the current evidence on the safety and efficacy of these two agents and to provide a perspective on why their repurposing has hitherto failed.MethodsPublished studies and rapidly emerging data were reviewed to gather evidence on safety and efficacy of CQ and HCQ in patients with COVID‐19 infection or as prophylaxis. The focus is on clinically relevant efficacy endpoints and their adverse effects on QT interval.Results and DiscussionAt the doses used, the two agents, given alone or with azithromycin (AZM), are not effective in COVID‐19 infection. The choice of (typically subtherapeutic) dosing regimens, influenced partly by "QT‐phobia," varied widely and seems anecdotal without any pharmacologically reliable supporting clinical evidence. A substantial proportion of patients receiving CQ/HCQ/AZM regimen developed QTc interval prolongation, many with absolute QTc interval exceeding the potential proarrhythmic threshold, but very few developed proarrhythmia.What is new and ConclusionThe strategy to repurpose CQ/HCQ to combat COVID‐19 infection is overshadowed by concerns about their QT liability, resulting in choice of potentially subtherapeutic doses. Although the risk of QT‐related proarrhythmia is real, it is low and manageable by careful monitoring. Recent discontinuation of HCQ from at least four large studies effectively marks the end of efforts at repurposing of CQ or HCQ for COVID‐19 infection. This episode leaves behind important questions on dose selection and risk/benefit balance in repurposing drugs generally.

Discontinuation of hydroxychloroquine in older patients with systemic lupus erythematosus: a multicenter retrospective study

BackgroundAlthough hydroxychloroquine (HCQ) is a mainstay of treatment for patients with systemic lupus erythematosus (SLE), ocular toxicity can result from accumulated exposure. As the longevity of patients with SLE improves, data are needed to balance the risk of ocular toxicity and the risk of disease flare, especially in older patients with quiescent disease. Accordingly, this study was initiated to examine the safety of HCQ withdrawal in older SLE patients.MethodsData were obtained by retrospective chart review at three major lupus centers in New York City. Twenty-six patients who discontinued HCQ and thirty-two patients on HCQ matched for gender, race/ethnicity, and age were included in this study. The primary outcome was the occurrence of a lupus flare classified by the revised version of the Safety of Estrogens in Lupus Erythematosus: National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) Flare composite index, within 1 year of HCQ withdrawal or matched time of continuation.ResultsFive patients (19.2%) in the HCQ withdrawal group compared to five (15.6%) in the HCQ continuation group experienced a flare of any severity (odds ratio [OR] = 1.28; 95% CI 0.31, 5.30; p = 0.73). There were no severe flares in either group. The results were similar after adjusting for length of SLE, number of American College of Rheumatology criteria, low complement levels, and SELENA-SLEDAI score, and in a propensity score analysis (OR = 1.18; 95% CI 0.23, 6.16; p = 0.84). The analysis of time to any flare revealed a non-significant earlier time to flare in the HCQ withdrawal group (log-rank p = 0.67). Most flares were in the cutaneous and musculoskeletal systems, but one patient in the continuation group developed pericarditis. The most common reason for HCQ withdrawal was retinal toxicity (42.3%), followed by patient’s preference (34.6%), other confirmed or suspected adverse effects (15.4%), ophthalmologist recommendation for macular degeneration (3.8%), and rheumatologist recommendation for quiescent SLE (3.8%).ConclusionsIn this retrospective study of older stable patients with SLE on long-term HCQ, withdrawal did not significantly increase the risk of flares.

Prevalence of hydroxychloroquine-induced side-effects in dermatology patients: A retrospective survey of 102patients

Our aim was to assess the prevalence of adverse effects (AEs) pertaining to the use and withdrawal of hydroxychloroquine (HCQ) in dermatological outpatients. We conducted a retrospective study between January 2013 and June 2014 that included consecutive patients currently or previously receiving HCQ seen in our department. AEs were collated using a standardized questionnaire and validated by clinical and laboratory examination. Drug causality was evaluated using the updated French drug reaction causality assessment method. The main evaluation criterion was the prevalence of AEs in which HCQ had an intrinsic imputability score of I>2. We included 102patients (93 of whom were women, with a median age of 44.5; range: 22-90years). HCQ was given for cutaneous lupus in most cases (n=70). At least one AE was reported for 55patients. Among the 91 reported AEs, 59 (65%) had an HCQ intrinsic imputability score I>2. AEs were responsible for permanent HCQ discontinuation in 19cases. Of these, 8 were unrelated to HCQ based on imputability score. The most common AEs associated with HCQ were gastrointestinal and cutaneous signs. Of the 8patients diagnosed with retinopathy, only 3 were confirmed after reevaluation. AEs associated with HCQ were reported for over 50% of patients and were responsible for permanent HCQ discontinuation in one-third of cases. A more in-depth evaluation of imputability seems necessary, particularly regarding ophthalmological symptoms, since in two thirds of cases the reasons for discontinuation were not related to HCQ.

Compliance and persistence with hydroxychloroquine in South Korean patients with systemic lupus erythematosus.

We aimed to analyze compliance and persistence with hydroxychloroquine (HCQ) in real practice and identify risk factors for poor adherence in South Korean patients with systemic lupus erythematosus (SLE). This retrospective longitudinal study evaluated 235 SLE patients in whom oral HCQ was newly started from 2002 to 2016 at a tertiary hospital in South Korea. Compliance was assessed using one-year medication possession ratio (MPR) and non-compliance was defined as a one-year MPR < 0.8. Persistence was determined as the time from HCQ treatment initiation to discontinuation without interruption for ≥56 days. The mean one-year MPR of HCQ was 0.88 and the frequency of non-compliance was 19.9%. During the study period, 115 (48.9%) patients discontinued HCQ and forgetfulness and/or carelessness (73%) were the most common reason for HCQ non-persistence, followed by adverse events (10.4%), unknown factors (10.4%), and pregnancy (6.1%). Median duration until HCQ discontinuation was 55.1 months and the one-year persistence rate to HCQ was 0.8. SLE Disease Activity Index 2000 (SLEDAI-2K) < 6 was a significant risk factor for non-compliance (OR = 2.98, p = 0.001) and non-persistence (HR = 1.55, p = 0.046) with HCQ after adjusting confounding factors. However, HCQ adherence was not associated with the dose of HCQ or concomitant immunosuppressive medications. Our data showed that overall adherence to HCQ in SLE patients was suboptimal in real practice and SLEDAI-2K score < 6 was a risk factor for poor adherence, suggesting the need to improve adherence with HCQ treatment in SLE patients, especially in those with low disease activity.

LOSS OF EXTERNAL LIMITING MEMBRANE INTEGRITY PREDICTS PROGRESSION OF HYDROXYCHLOROQUINE RETINAL TOXICITY AFTER DRUG DISCONTINUATION.

To quantify external limiting membrane (ELM) disruption and photoreceptor volume over time, using spectral domain optical coherence tomography in eyes with hydroxychloroquine (HCQ) toxic effects after discontinuation. We performed a retrospective chart review of patients who were screened for toxic effects of HCQ between January 1, 2009 and August 31, 2014, and identified 10 patients diagnosed as having HCQ retinal toxic effects. Intact ELM and the Bruch membrane were manually traced using ImageJ software and their lengths from each scan of the spectral domain optical coherence tomography macular volume were summed. The ratio of intact ELM length/Bruch membrane length was calculated. We measured the two-dimensional photoreceptor area between the intact ELM and Bruch membrane in every cross-sectional B-scan. We calculated the total volume of photoreceptors in a volumetric OCT by multiplying photoreceptor area by the distance between B-scans. Of the 10 patients (120 eyes), 1 eye was excluded because of the presence of vitreomacular traction. The mean cumulative dose of HCQ was 1,951 g (range, 584-3,650 g). The mean follow-up duration was 34.1 months (range, 11-64 months). Based on the extent of ELM integrity at diagnosis of HCQ toxicity, we classified eyes into 2 groups: 1) 12 eyes showed severe ELM disruption and 2) 7 eyes had intact ELM. All 19 eyes showed characteristic signs of HCQ toxicity on the visual field examination at the baseline. Seven of 12 eyes with ELM disruption showed progressive ELM changes, including 7 eyes that additionally developed progressive photoreceptor volume decline, whereas 5 eyes remained stable. All 7 eyes with intact ELM remained stable over time. Intact ELM status at the time of HCQ discontinuation is a good prognostic sign, and ELM status may allow clinicians to predict patients at risk for progression of retinopathy. Quantitative measurements of ELM disruption and photoreceptors volume may provide an objective tool to monitor outer retinal changes due to HCQ.

Assessment of hydroxychloroquine maculopathy after cessation of treatment: an optical coherence tomography and multifocal electroretinography study.

ObjectiveThis study was conducted to evaluate the macular status of patients treated with hydroxychloroquine before and after cessation of treatment.MethodsForty-two patients with systemic lupus erythematosus underwent ocular examination based on visual acuity evaluation, optical coherence tomography retinal thickness measurements, and multifocal electroretinography (mfERG) records at first visit. The tests were repeated 6 months after treatment withdrawal and compared to the findings at their first visit.ResultsMean visual acuity (measured in log minimum angle of resolution) of both eyes was statistically increased after hydroxychloroquine discontinuation (difference in means: 0.06 [P<0.0001] and 0.01 [P=0.003] for the right and left eyes, respectively). Retinal response amplitudes of central and peripheral areas were significantly improved for both eyes. The following values were observed for central responses: the difference in means was −19.9 (P<0.0001) and −13.6 (P<0.0001) for the right eye and the left eye, respectively; for peripheral responses, difference in means was −10.3 (P<0.0001) and −9.5 (P<0.0001) for right eye and left eye, respectively, after the 6-month examination. There were no statistically significant differences in the retinal thickness of patients after cessation of treatment. The visual acuity of the patients was correlated to central and peripheral mfERG responses (r=−0.53 [P<0.0001] and r=−0.53 [P<0.0001], for the right eye and the left eye, respectively).ConclusionThe visual acuity of patients receiving hydroxychloroquine improves along with the amplitudes of the mfERG responses 6 months after discontinuation of the drug, but no difference in retinal thickness is identified.

Pericentral Hydroxychloroquine Retinopathy in Korean Patients

A pericentral pattern of hydroxychloroquine (HCQ) retinopathy recently has been recognized in the United States in patients of Asian heritage. We report on an investigation of this pericentral retinopathy within a Korean population. Retrospective, observational study. Patients taking HCQ who were referred to ophthalmology for screening of HCQ retinopathy. The medical records of patients were reviewed, including spectral domain optical coherence tomography, fundus autofluorescence, and visual fields. Frequency of pericentral pattern of HCQ retinopathy and features of progression. Among 218 patients referred, 9 (4.1%) were diagnosed with toxicity. Of these, 8 had a predominantly pericentral pattern of retinal change, whereas only 1 had the classic parafoveal distribution of retinal damage. Progression of retinopathy was documented in 3 patients followed more than 12 months while taking HCQ. No progression was seen in 2 patients without retinal pigment epithelial (RPE) damage who were followed for at least 12 months after discontinuation of HCQ. We found that a pericentral pattern of HCQ retinopathy was predominant among Korean patients, rather than the traditional (bull's eye) parafoveal pattern of damage. Retinopathy progressed while on the drug, but the progression stopped in patients with toxicity detected before RPE damage. These observations suggest the need for new approaches when screening for HCQ toxicity in Asian patients.

Hydroxychloroquine and pregnancy on lupus flares in Korean patients with systemic lupus erythematosus.

We investigated the clinical and laboratory characteristics of pregnancies with systemic lupus erythematosus (SLE) and identified lupus flare predictors during pregnancy. Additionally, we examined lupus activity and pregnancy outcomes in SLE patients who continued, discontinued or underwent no hydroxychloroquine (HCQ) treatment during pregnancy. We retrospectively analyzed 179 pregnancies in 128 SLE patients at Seoul St. Mary's Hospital, Korea, between 1998 and 2012 and then assessed the clinical profiles and maternal and fetal outcomes. Overall, 90.5% of pregnancies resulted in a successful delivery and were divided into two groups: those who experienced lupus flares (80 pregnancies, 44.7%) and those who did not (99 pregnancies, 55.3%). Increased preeclampsia, preterm births, low birth weight, intrauterine growth restriction (IUGR), and low 1-minute Apgar scores occurred in pregnancies with lupus flares compared to pregnancies in quiescent disease. Lupus flares were predicted by HCQ discontinuation, a history of lupus nephritis, high pre-pregnancy serum uric acid and low C4 levels. Our study indicates that achieving pre-pregnancy remission and continuing HCQ treatment during pregnancy are important for preventing lupus flares.