Latest news with #hydroxychloroquine
Medscape
03-07-2025
- Health
- Medscape
Abatacept Beats HCQ in Halting RA in Palindromic Rheumatism
TOPLINE: Abatacept outperformed hydroxychloroquine (HCQ) in preventing patients with palindromic rheumatism (PR) from progressing to rheumatoid arthritis (RA). METHODOLOGY: Researchers randomly assigned 70 individuals with PR who were seropositive for rheumatoid factor or anti-citrullinated protein antibodies in a 1:1 ratio to receive open-label abatacept (ABA) at 125 mg/week or HCQ at 5 mg/kg/day for 1 year. All patients had symptom durations of over 3 months but under 3 years and were not taking any disease-modifying antirheumatic drugs or glucocorticoids. Patients were followed for an additional year to track RA development. TAKEAWAY: At month 24, three patients (8.8%) in the ABA group progressed to RA compared with 10 patients (27.8%) in the HCQ group (P = .047). Patients treated with HCQ who developed RA generally progressed in the first 12 months of the trial, whereas patients treated with ABA who developed RA did so at the end of the second year. The ABA group also had higher persistent remission rates of PR than the HCQ group (55.9% vs 22.9%). Serious adverse events were uncommon in both treatment groups. IN PRACTICE: 'In patients with recent-onset seropositive palindromic rheumatism, abatacept significantly decreased the rate of RA progression in comparison with hydroxychloroquine at 2 years follow-up,' said study author Raimon Sanmarti, MD, PhD, of the Hospital Clínic de Barcelona, Barcelona, Spain. 'Abatacept is also more efficacious than hydroxychloroquine in the control of symptoms of seropositive palindromic rheumatism.' SOURCE: Sanmarti presented the study in an oral abstract session at the European Alliance of Associations for Rheumatology (EULAR) 2025 Annual Meeting. LIMITATIONS: This was an open-label study with a relatively small sample of patients. Over the 2-year trial, eight patients in the HCQ group and five patients in the ABA group exited the trial or were lost to follow-up. DISCLOSURES: The Fundació Clínic per a la Recerca Biomèdica sponsored the study. Sanmarti disclosed financial relationships with Bristol Myers Squibb, AbbVie, MSD, Roche, UCB, Pfizer, Eli Lilly, Gebro, Janssen, Sanofi, Gilead, and Adacyte.
Medscape
27-06-2025
- Health
- Medscape
Hydroxychloroquine May Tame Preeclampsia in Lupus Patients
Use of hydroxychloroquine during pregnancy in patients with systemic lupus erythematosus (SLE) is associated with a reduced risk for preeclampsia, according to a recent nationwide cohort study. A population-based analysis from Sweden found that women with SLE taking hydroxychloroquine had about half the risk for preeclampsia compared with those not taking it, but there was no clear association between hydroxychloroquine use and preterm birth risk. 'These findings suggest possibly favorable, or at least not harmful, associations between hydroxychloroquine and preeclampsia and preterm delivery in pregnancies in women with SLE, supporting the current recommendations for hydroxychloroquine treatment during pregnancy in these patients,' wrote Ngoc V. Nguyen, MPH, a PhD candidate at the Karolinska Institutet in Stockholm, Sweden, and his colleagues in The Lancet Rheumatology . '[Hydroxychloroquine] may actually reduce the risk of preeclampsia,' Nguyen told Medscape Medical News . Joshua Copel, MD, a professor of obstetricis, gynecology, and reproductive sciences and of pediatrics at Yale School of Medicine, New Haven, Connecticut, told Medscape Medical News the findings show that 'hydroxychloroquine certainly doesn't seem to cause an increased risk for spontaneous preterm birth, and it probably reduces the risk for preeclampsia or at least delays the onset of preeclampsia.' The researchers used the Swedish Medical Birth Register to identify all 959 singleton pregnancies among 685 women with SLE in Sweden between January 2007 and December 2022. Using the Prescribed Drug Register, they determined which patients had received at least two dispensations between 3 months before pregnancy through the end of the first trimester. Among the 42% of pregnancies that were nulliparous, 43% were exposed to hydroxychloroquine and 57% were unexposed. Among the other 58% of pregnancies that were parous, 40% were exposed and 60% were unexposed. Patients had an average age of 32 years and an average first-trimester BMI ranging from 23.7 to 24.9 across the different groups. They had been diagnosed with lupus for 5.4-6.8 years, and rates of prior miscarriages ranged from 19% to 38% across the groups. Preeclampsia occurred in 11% of exposed and 13% of unexposed nulliparous pregnancies and in 5% of exposed and 6% of unexposed parous pregnancies. Preterm birth occurred in 19% of exposed and 15% of unexposed nulliparous pregnancies and in 12% of exposed and 12% of unexposed parous pregnancies. After adjustment for confounders, these numbers translated to an overall 49% reduced risk for preeclampsia in those exposed to hydroxychloroquine (95% CI, 0.31-0.79; P = .003). Stratified by parity, however, the 59% preeclampsia risk reduction in nulliparous pregnancies exceeded the threshold for statistical significance (95% CI, 0.33-1.08; P = .085). The 44% reduction in parous pregnancies was significant (95% CI, 0.22-0.89; P = .02). Questions Remain Though these findings 'add to a growing body of evidence suggesting hydroxychloroquine may help lower the risk of preeclampsia,' Nguyen told Medscape Medical News , 'it's worth noting that not all studies have shown statistically significant effects [potentially because of] how hydroxychloroquine use was defined, how well patients adhered to it, or whether key factors like BMI and smoking were accounted for.' Alfred Kim, MD, PhD, an associate professor of rheumatology at Washington University Medicine in St. Louis, told Medscape Medical News that hydroxychloroquine 'has a well-established antithrombotic property,' as seen with antiphospholipid syndrome, and 'preeclampsia is a prothrombotic condition due to substantial endothelial dysfunction, driving complement and coagulation cascade activation.' 'It is not completely clear how hydroxychloroquine attenuates thrombosis, though,' Kim said. 'There are nice data suggesting that hydroxychloroquine inhibits platelet activation and thrombus formation, both of which can promote a preeclamptic state.' Other possibilities, Nguyen added, include antioxidant activity, improved placental perfusion, and stabilization of endothelial function, any of which could also, in theory, reduce the risk for preterm birth in certain cases. However, this study found no association with preterm birth overall (risk ratio [RR], 0.95; 95% CI, 0.67-1.34; P = .76), in nulliparous births (RR, 1.1; P = .69), or in parous births (RR, 0.75; P = .28). Adherence Barriers Present Challenges Grégoire Martin de Frémont, Gaëlle Guettrot-Imbert, and Nathalie Costedoat-Chalumeau of Paris City University in Paris wrote in an accompanying editorial in The Lancet Rheumatology that 'by suggesting a beneficial effect on preeclampsia, the rigorous and valuable findings reported by the authors provide an additional rationale for the use of hydroxychloroquine in all pregnant women with SLE, as currently recommended.' They add, however, that 'obstacles to its optimal use persist, including drug unavailability, lack of prescription, and, in many cases, patients' reluctance to take it.' Kim agreed that many barriers remain to hydroxychloroquine adherence during pregnancy. 'Sometimes it's due to the patient not fulfilling the prescription, whether this is due to cost — which is typically not an issue with hydroxychloroquine — to inadequate comprehension due to low literacy, cognitive issues, language or visual barriers to a lack of trust in the medication or the medical team prescribing hydroxychloroquine,' Kim said. Nguyen agreed that the challenge of adherence is complex, with hurdles that include misinformation about safety, mixed messages from providers, and challenges such as age, disease severity, or pill burden. 'Our study might help chip away at some of these barriers by offering strong evidence for benefit, not just safety. If we can reframe hydroxychloroquine as something that's protective during pregnancy — not just 'safe enough' — that might help patients feel more comfortable and providers more proactive,' he said. The research was funded by the US National Institutes of Health and the Ingegerd Johansson Donation. The authors reported no disclosures. Costedoat-Chalumeau reported grants from UCB and Roche and honoraria from Bristol Myers Squibb. Copel serves on the advisory board for Janssen Pharmaceuticals, Nuvo, SimHawk, and Pulsenmore; receives royalties from Elsevier and UpToDate; and owns a company that manufactures prenatal vitamins. Kim receives royalties from Kypha Inc.; sponsored research agreements with AstraZeneca, Bristol Myers Squibb, CRISPR Therapeutics, and Novartis; and has done consulting or speaking for AbbVie, Amgen, Atara Biotherapeutics, Aurinia Pharmaceuticals, Cargo Tx, Exagen Diagnostics, GlaxoSmithKline, Genentech/Roche, Hinge Bio, Invivyd, Johnson & Johnson, UpToDate, and Zenas BioPharma.
Medscape
18-06-2025
- Health
- Medscape
Leflunomide, HCQ Combo Effects Validated in Sjögren Disease
BARCELONA, Spain — In the treatment of primary Sjögren disease, the use of leflunomide (LEF) and hydroxychloroquine (HCQ) in combination was associated with a greater reduction in disease activity than placebo, according to new trial results reported at the European Alliance of Associations for Rheumatology (EULAR) 2025 Annual Meeting. In the randomized controlled RepurpSS-II trial, the LEF-HCQ combination produced a mean decrease in EULAR Sjögren syndrome disease activity index (ESSDAI) score of 4.13 points ( P = .001) relative to placebo after 24 weeks of treatment. There were also greater reductions in serum immunoglobulin G, rheumatoid factor, and complement component 4 with the combination than with placebo. However, there were no differences between the groups in terms of patients' symptoms as measured by the EULAR Sjögren syndrome patient reported index (ESSPRI) or its separate components. There were also no differences between the groups in improving dryness as measured using the Schirmer and unstimulated saliva tests. Confirmatory Trial Wing-Yi Wong, MD 'The major challenge in this disease is the lack of standard treatments, despite the need,' said Wing-Yi Wong, MD, a PhD student at University Medical Center Utrecht, Utrecht, the Netherlands, who presented the findings as a late-breaking abstract. 'Many trials in the past 40 years have failed to show clinical efficacy,' Wong added. One of the few trials that had proven promising previously, however, was the RepurpSS-I trial, which had tested a combination of LEF at a dose of 20 mg/d and HCQ at a dose of 400 mg/d given for 24 weeks vs placebo. RepurpSS-II was set up to confirm the findings of RepurpSS-I. Published in The Lancet Rheumatology in 2020, RepurpSS-I had shown that LEF-HCQ reduced ESSDAI a mean of 4.29 points more than that with placebo. Trial Designs and RepurpSS-II Population RepurpSS-I was a phase 2a trial, and RepurpSS-II was a phase b2 trial. Entry criteria were similar for both trials: Primary Sjögren disease diagnosis, an ESSDAI ≥ 5, and no significant comorbidities. Women of a child-bearing age also had to be taking reliable contraception. Both RepurpSS trials included 24-week double-blind treatment phases, with RepurpSS-II adding a single-arm crossover extension for a further 24 weeks. A total of 37 people with primary Sjögren disease had been screened for inclusion in RepurpSS-I, 29 were included, 21 of whom were treated with the LEF-HCQ combination and eight with placebo. For RepurpSS-II, 85 of 233 people who were considered for inclusion were screened, and 46 were included in the trial. Of these, 21 were treated with LEF-HCQ and 25 with placebo. Among the reasons for not screening or including more people in RepurpSS-II were comorbidities; current or recent treatment with LEF, HCQ, or other disease-modifying antirheumatic drugs; and not meeting other entry criteria. Participants in the LEF-HCQ and placebo groups of RepurpSS-II were demographically similar: The mean age was 55 years; 90.5% and 96.0%, respectively, were women; and the mean disease durations were 6.5 years and 10.0 years, respectively. Mean ESSDAI scores at baseline were 9.52 in the LEF-HCQ group and 9.88 in the placebo group, and mean ESSPRI scores were 7.00 and 6.83, respectively. Other Findings Exploratory analyses using the Sjögren's Tool for Assessing Response (STAR) and the Composite of Relevant Endpoints for Sjögren Syndrome (CRESS) also favored LEF-HCQ. 'STAR and CRESS scores are two novel composite endpoints that includes patient-reported outcomes together with objective measures of dryness alongside the clinical ESSDAI,' Wong said. She reported that there was a 'significantly higher percentage of responders' in the LEF-HCQ group using both measures vs placebo. Adverse event rates were similar between groups: A total of 58 events occurred in the LEF-HCQ group and 57 in the placebo group. Most of these events were considered as mild (77.6% for LEF-HCQ and 66.7% for placebo), with gastrointestinal discomfort and respiratory infections among the most commonly reported. Two severe adverse events occurred, one in each group, and were deemed unrelated to the study treatment. The one in the LEF-HCQ group was a non-ST elevation myocardial infarction, and the one in the placebo group was an allergic reaction to antibiotic treatment. A total of 14 patients in the LEF-HCQ group completed the double-blind phase, and nine chose to enter the 24-week, open-label extension. Although completed, results of this phase are pending. 'Overall, the combination treatment was well tolerated, and leflunomide-hydroxychloroquine is realistic treatment option, which is affordable, accessible, and widely available,' Wong concluded. This study was funded by the Dutch independent government body ZonMw . Wong and fellow investigators for the RepurpSS-II study had no relevant conflicts of interest.
Medscape
13-06-2025
- Health
- Medscape
Time to Monitor Serum Hydroxychloroquine Levels in Lupus?
BARCELONA, Spain — Monitoring serum hydroxychloroquine levels could help to ensure that patients with systemic lupus erythematosus (SLE) are being treated with the drug optimally, according to research reported at European Alliance of Associations for Rheumatology (EULAR) 2025 Annual Meeting. Shivani Garg, MD, PhD Shivani Garg, MD, PhD, an assistant professor of medicine and medical director of the Lupus and Lupus Nephritis Clinics at the School of Medicine and Public Health, University of Wisconsin-Madison, presented the findings of an observational study that confirmed and extended the results from an earlier study carried out by her research group that the ideal serum hydroxychloroquine level lay somewhere between a lower limit of 750 ng/mL and an upper limit of 1150 ng/mL for most patients with SLE. The new study also showed that as estimated glomerular filtration rate (eGFR) increases, so does serum levels of hydroxychloroquine in the blood. This suggested that monitoring serum hydroxychloroquine levels may be particularly useful in people with chronic kidney disease. Justification to Monitor Alfred Kim, MD, PhD Alfred Kim, MD, PhD, told Medscape Medical News that Garg's data gave justification to the idea that serum hydroxychloroquine levels need to be checked as a matter of routine. 'I think rheumatologists have been behind in checking drug blood levels in general. We don't check as routinely as compared to say nephrologists and gastroenterologists,' said Kim, who is an associate professor of medicine and associate professor of pathology and immunology at Washington University School of Medicine, St. Louis. One of the known long-term risks associated with taking hydroxychloroquine is retinal toxicity, which is why regular eye examinations are undertaken. It takes time for the eye damage to accumulate, however, so 'how do you assume without knowing the levels that you're actually not introducing risk or not knowingly introducing risk downstream?' Kim said there has been a tendency 'to follow clinical response and assume that if patients are not showing acute toxicity, that there will be no long-term toxicity.' This is 'obviously incorrect,' he said, and added that a 'culture change' is happening. Optimum Dose Debated 'Hydroxychloroquine, or HCQ, is the cornerstone of lupus treatment as it prolongs both disease- and damage-free survival. However, the optimum dose of hydroxychloroquine is under great debate,' Garg said during her presentation. Hydroxychloroquine is dosed according to body weight, with a recommended dose of 5 mg/kg. Prior data have shown that doses above this level double the risk for retinopathy compared with the level of 4-5 mg/kg/d, while those at 5 mg/kg/d or below are associated with a two- to six-fold increased risk for disease flares. Measuring serum levels of hydroxychloroquine reflects metabolism, clearance, and adherence, Garg argued, and thus measuring and monitoring these levels could be a potential solution to ensuring the perfect balance between toxicity and efficacy. Considering that 65% of hydroxychloroquine is cleared by the kidneys, one of the aims of the study was to identify if there are any thresholds of kidney function associated with supratherapeutic levels over time. Study Design and Findings Garg and colleagues combined prospectively collected data from two longitudinal cohorts from France and the US, encompassing a total of 1240 patients with SLE who had been treated with hydroxychloroquine. The median age of the cohort was 40 years, and 92% were women. Just over half (58%) were being treated with doses of more than 5 mg/kg/d and 42% with doses of 5 mg/kg/d or lower. The cumulative hydroxychloroquine dose was 2318 g, and mean serum levels of the drug were 947 ng/mL. The mean SLE Disease Activity Index (SLEDAI) was 2.8, and 4.4% had experienced cardiac or retinal toxicity. On the first study visit, patients gave whole blood samples to have serum hydroxychloroquine levels measured using liquid chromatography in tandem with mass spectrometry or mass spectrometry alone. Researchers collated data on patient outcomes, including disease activity measured by SLEDAI, and toxicity, notably retinopathy and cardiotoxicity. Analyses were then performed to find the upper threshold for serum hydroxychloroquine levels at which toxicity occurred and the threshold at which a 'ceiling effect' for disease response occurred. Data were also analyzed according to patients' eGFR at the baseline visit, and any subsequent visits if available. Results showed that serum hydroxychloroquine levels in excess of 1150 ng/mL were associated with 2.2-fold increased risk for systemic toxicity, even after excluding retinopathy. Moreover, serum hydroxychloroquine levels above this limit did not appear to provide any further clinical benefit. Results also showed that having an eGFR < 60 mL/min/1.73 m2— indicating stage 3 or greater chronic kidney disease — was associated with a 2.5-fold greater likelihood of serum hydroxychloroquine levels in excess of 1150 ng/mL, risking toxicity. Garg told Medscape Medical News: 'Right now, we don't monitor because we didn't know how to interpret the [serum] levels. This study gave data on this.' In the long run, the findings could mean that patients with serum hydroxychloroquine levels within the proposed target 'get a green check. But if the levels are too high, you might need to scale down the dose.' This study received no commercial funding. Garg and Kim had no financial disclosures or conflicts of interest to report.
Medscape
14-05-2025
- Health
- Medscape
Lupus Drug Withdrawal: Immunosuppressants or Steroids First?
In patients with systemic lupus erythematosus (SLE) who had been in remission for at least 1 year, immunosuppressant withdrawal was noninferior to glucocorticoid withdrawal, with no significant differences in the proportion of patients who experienced flares or in flare severity at 1- and 2-year follow-ups. METHODOLOGY: Researchers conducted a randomized noninferiority trial at a tertiary hospital in India (between May 2021 and December 2023) to compare the outcomes of immunosuppressant withdrawal with those of glucocorticoid withdrawal in adult patients with SLE in remission. They included 117 patients with SLE who had received treatment for at least 3 years, had been in remission for at least 1 year, and were receiving glucocorticoids (≤ 7.5 mg/d of prednisolone) along with one maintenance immunosuppressant. Patients were randomly assigned to one of the two groups: One tapered off prednisolone over 3 months while continuing immunosuppressants (n = 58; median age, 35 years; 98.3% women) and the other tapered off immunosuppressants while maintaining low-dose prednisolone (n = 59; median age, 36 years; 93.2% women). All patients continued receiving hydroxychloroquine. The primary outcome was the proportion of patients who experienced a flare, as defined by the SELENA-SLEDAI Flare Index, at any time up to 52 weeks, with follow-up extending up to and beyond 104 weeks. Noninferiority of immunosuppressant over glucocorticoid withdrawal was confirmed if the upper limit of the 95% CI for the between-group difference in the proportion of patients who experienced a flare was < 10%. TAKEAWAY: At 52 weeks and at maximum follow-up, the proportion of patients who experienced a flare did not differ significantly between the immunosuppressant and glucocorticoid withdrawal groups, with the risk difference between the groups indicating the noninferiority of immunosuppressant withdrawal. At the maximum follow-up, 55.2% of patients in the glucocorticoid withdrawal group and 67.8% of those in the immunosuppressant withdrawal group did not experience a flare. Among those who did, mild to moderate flares were most common. Damage accrual did not differ significantly between the two groups at maximum follow-up. Low baseline complement C3 levels were identified as a predictor of flares at both 52 weeks (hazard ratio [HR], 3.698; P = .012) and at maximum follow-up (HR, 3.785; P = .001). IN PRACTICE: 'Our results suggest that low-dose GCs [glucocorticoids], combined with HCQ [hydroxychloroquine], may be a viable long-term maintenance option for managing SLE patients in sustained remission,' the authors wrote. 'Based on our findings, it is evident that a one-size-fits-all approach to IS [immunosuppressant] or GC withdrawal may not be ideal. Instead, a personalized tapering approach considering patient risk profile, prior damage, and steroid exposure may help mitigate adverse events while maintaining disease control,' they added. SOURCE: This study was led by Aishwarya Gopal, MD, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India. It was published online on March 24, 2025, in Rheumatology . LIMITATIONS: This study had an open-label design and lacked a control arm that continued all medications. Adrenal insufficiency upon flares was not tested in patients who underwent steroid withdrawal. Remote access to glucocorticoids could not be ruled out. DISCLOSURES: This study received funding from Jawaharlal Institute of Postgraduate Medical Education and Research. The authors declared having no conflicts of interest.
