Effects of hydroxychloroquine and its metabolites in patients with connective tissue diseases

Onmaz, Duygu Eryavuz; Tezcan, Dilek; Abuşoğlu, Sedat; Yılmaz, Sema Dereli; Yerlikaya, Fatma Hümeyra; Onmaz, Mustafa; Abuşoğlu, Gülsüm; Ünlü, Ali

doi:10.1007/s10787-021-00887-8

Cited by 7 publications

(4 citation statements)

References 38 publications

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“…Although patients with COVID-19 have been treated with HCQ, concerns have been raised regarding its effectiveness and safety. 38,39 Targeting T-helper 17 cells, B-cell activating factors, the Janus kinase pathway, mesenchymal stromal cell therapy, and combined strategies might have the potential for treating new-onset pSS triggered by SARS-CoV-2. [40][41][42] Rheumatologists should continue to identify patients with a history of vaccination and SARS-CoV-2 infection at the initial presentation, and even consider expanding the use of the ESSDAI.…”

Section: Discussionmentioning

confidence: 99%

“…This might have been associated with greater disease activity because splenomegaly induces hematopaenia and worsens nonspecific interstitial pneumonia on lung CT images. Although patients with COVID‐19 have been treated with HCQ, concerns have been raised regarding its effectiveness and safety 38,39 . Targeting T‐helper 17 cells, B‐cell activating factors, the Janus kinase pathway, mesenchymal stromal cell therapy, and combined strategies might have the potential for treating new‐onset pSS triggered by SARS‐CoV‐2 40–42 .…”

Section: Discussionmentioning

confidence: 99%

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New‐onset primary Sjögren's syndrome following exposure to severe acute respiratory syndrome coronavirus 2: A retrospective cohort study

Liu,

Zhang,

Liu

et al. 2024

Rheumatology & Autoimmunity

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BackgroundUnderstanding the clinical implications of autoimmune manifestations associated with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is essential to reduce its consequences. This study was aimed at determining the activities of new‐onset primary Sjögren syndrome (pSS) since the emergence of SARS‐CoV‐2.MethodsThis retrospective cohort study included data from 471 participants with dry mouths and eyes who had been attending Nanjing Drum Tower Hospital since December 2019. By April 2023, patients diagnosed with pSS were sequentially assigned to vaccinated group (n = 24) or vaccinated and infected group based on exposure (n = 20). Patients diagnosed with pSS within 3 months of vaccination against SARS‐CoV‐2 were assigned to a vaccinated group, and those who had been vaccinated and then developed pSS within 3 months of follow up after direct exposure to SARS‐CoV‐2 were assigned to a vaccinated and infected group. The controls comprised age‐ and sex‐matched patients who had not been exposed to SARS‐CoV‐2 before December 2019 (n = 21). We then compared data among the three groups.ResultsThe vaccinated and infected patients had more fever, malaise, splenomegaly, and weight loss before diagnosis and a higher European Alliance of Associations for Rheumatology Sjögren's syndrome disease activity index at the time of onset than the other two groups. Vaccinated patients had a higher frequency of anti‐nuclear antibody (ANA) titers > 1:320 (n = 12; 50%) and anti‐phospholipid antibodies (aPL) (n = 7; 29%) than the controls. The frequency of anti‐Ro/SSA antibodies (13, 65%), ANA titers > 1:320 (n = 16; 80%), and aPLs (n = 7; 29%) (n = 5; 25%) were all significantly higher in vaccinated patients with infection than those in the controls. Higher doses of glucocorticoids, cyclosporin A, and tacrolimus were administered to the vaccinated and infected than the vaccinated and control groups (p < 0.05, for all).ConclusionsPatients with new‐onset pSS and a history of vaccination and SARS‐CoV‐2 infection might have more active disease. Further strengthening the assessment of people with a clear history of SARS‐CoV infection and the monitoring of potential populations for autoimmune screening should not be overlooked.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

New‐onset primary Sjögren's syndrome following exposure to severe acute respiratory syndrome coronavirus 2: A retrospective cohort study

Liu,

Zhang,

Liu

et al. 2024

Rheumatology & Autoimmunity

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“…The median concentration in peripheral blood for HCQ, DHCQ, DCQ, and BDCQ from Eryavuz Onmaz’s investigation was 806 (range 61.7–2760), 452 (range 20.0–1700), 76.4 (range 4.0–502.0), and 291 (range 14.0–1477) ng/mL, respectively. 42 In comparison, the average concentration of HCQ and its metabolites detected in our study was relatively lower [563.31 (376.39, 794.22), 355.24 (262.27, 482.30), 44.73 (36.55, 80.63), and 27.22 (14.79, 36.66) ng/mL for HCQ, DHCQ, DCQ, and BDCQ, respectively, Table 1 ], which might be attributed to the different HCQ metabolism by various races or inconsistent detection methods. By employing OCT and mfERG as the assessment method for fundus oculi, Petri et al 43 reported that HCQ blood concentration was related to retinal changes, while Munster found that high HCQ concentration in blood was associated with gastrointestinal side effects rather than retinal toxicity.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of early retinal changes in patients on long-term hydroxychloroquine using optical coherence tomography angiography

Zhao,

Pan,

Liu

et al. 2024

Therapeutic Advances in Drug Safety

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Background: Connective tissue diseases (CTD), including systemic lupus erythematosus and rheumatoid arthritis (RA), have long been treated with hydroxychloroquine (HCQ). However, prolonged HCQ use poses a risk of adverse effects, particularly retinopathy. Objective: To detect early retinal changes assessed by optical coherence tomography angiography (OCTA) in CTD patients with long-term HCQ treatment and to explore the relationship between OCTA parameters and the concentrations of HCQ and its metabolites. Design: A cross-sectional study conducted from March 2020 to October 2021 at the First Affiliated Hospital of Anhui Medical University. Methods: The area and perimeter of the foveal avascular zone (FAZ), the thickness of the fovea and parafovea, and the vascular density of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) in each area of the macula were measured by OCTA in 43 CTD patients treated with HCQ for over 6 months. Meantime, blood concentrations of HCQ and its metabolites were determined by high-performance liquid chromatography-tandem mass spectrometry, and the clinical documents of all 43 involved patients were collected. Results: There is no significant correlation between OCTA outcomes and the patient’s age, disease duration, and weight-dependent dose. HCQ cumulative duration positively correlated with FAZ area and perimeter ( r = 0.419, p = 0.005 and r = 0.407, p = 0.007, respectively) and negatively correlated with the foveal vessel density in DCP ( r = −0.378, p = 0.012). HCQ cumulative dose had a positive correlation with FAZ area and perimeter ( r = 0.445, p = 0.003 and r = 0.434, p = 0.004, respectively) and had a negative correlation with foveal vessel density in SCP and DCP ( r = −0.383, p = 0.011 and r = −0.424, p = 0.005, respectively). OCTA outcomes did not correlate with HCQ and its metabolite concentrations. Conclusion: OCTA could be used to detect microvascular changes in the macula of CTD patients with long-term HCQ therapy. It was not found the concentrations of HCQ and its metabolites were associated with retinal vascular changes.

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“…O nosso estudo fornece dados novos sobre a adesão medicamentosa à HCQ nos pacientes com DSj, um aspecto relevante para a prática clínica e que não havia sido abordado em estudos anteriores (Eryavuz Onmaz et al, 2021). De acordo com os níveis sanguíneos de HCQ, aproximadamente um terço dos nossos doentes com DSj apresentou não adesão grave (< 200 ng/mL) ou níveis subterapêuticos (200 -499 ng/mL), sendo que tais faixas haviam sido descritas previamente para os pacientes com LES (Durcan et al, 2015;Costedoat-Chalumeau et al, 2018;Cunha et al, 2018;Kang et al, 2023).…”

Section: Discussionunclassified

Avaliação dos níveis sanguíneos de hidroxicloroquina em pacientes com doença de Sjögren: adesão à medicação e correlações clínicas

Villamarin

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Introdução: A hidroxicloroquina (HCQ) é uma potencial opção de tratamento para a doença de Sjögren (DSj). No entanto, não existem estudos que avaliem a adesão medicamentosa através dos níveis sanguíneos de HCQ, refil de farmácia (RF) e questionários de adesão medicamentosa. Além disso, as possíveis associações dos níveis sanguíneos de HCQ com os parâmetros glandulares e extraglandulares da doença têm sido pouco avaliadas. Objetivos: Avaliar a adesão medicamentosa à HCQ na DSj por meio da determinação concomitante dos níveis sanguíneos desse medicamento e de instrumentos clínicos, bem como analisar as possíveis associações entre os níveis sanguíneos de HCQ e os vários parâmetros glandulares e extraglandulares da doença. Métodos: Esse estudo transversal observacional incluiu 74 pacientes adultos com DSj, que estavam recebendo uma dose estável de HCQ (4-5,5 mg/kg/dia, peso real) por pelo menos três meses antes da inclusão no estudo. Os níveis sanguíneos de HCQ foram determinados por cromatografia líquida de alta eficiência acoplada à espectrometria de massas (LC-MS/MS, do inglês, highperformance liquid chromatography coupled to mass spectrometry). A adesão ao medicamento foi avaliada pelo RF e pelo questionário de Medida de Adesão aos Tratamentos (MAT). Foram avaliados os seguintes parâmetros: Xerostomia Inventory (XI), Ocular Surface Disease Index (OSDI), EULAR (European League Against Rheumatism) Sjögren's Syndrome Patient Reported Index (ESSPRI), EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI), teste de Schirmer I e taxas de fluxo salivar não estimulado e estimulado. Resultados: A mediana dos níveis sanguíneos de HCQ foi de 775,3 (mínimo 25,0máximo 2.568,6) ng/mL. Onze pacientes (14,9%) apresentaram níveis sanguíneos de HCQ < 200 ng/mL (grupo não aderente); 11 (14,9%), 200 -499 ng/mL (grupo com níveis subterapêuticos); e 52 (70,2%), ≥ 500 ng/mL (grupo aderente). O RF classificou incorretamente todos os pacientes não aderentes/com níveis subterapêuticos e 2/52 (3,9%) dos pacientes aderentes. Usando o MAT, o erro de classificação geral foi 24/52 (46,2%) no grupo aderente; e foram identificados corretamente 9/11 (81,8%) dos pacientes não aderentes e 7/11 (63,6%) no grupo de níveis subterapêuticos. A sensibilidade e a especificidade do MAT para identificar pacientes não aderentes/com níveis subterapêuticos foram de 72,7% e 53,9%, respectivamente. Os três grupos foram comparáveis em relação aos parâmetros glandulares e extraglandulares da doença (P > 0,05). Conclusões: A avaliação dos níveis sanguíneos de HCQ é uma ferramenta promissora para avaliar a adesão medicamentosa na DSj. Isso é especialmente importante, pois um terço dos pacientes apresentou níveis de não adesão e subterapêuticos e os instrumentos de RF e o MAT não identificaram esses pacientes de forma consistente. Palavras-chave: Síndrome de Sjogren. Xerostomia. Síndromes do olho seco. Hidroxicloroquina. Antimaláricos. Adesão à medicação.

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Effects of hydroxychloroquine and its metabolites in patients with connective tissue diseases

Cited by 7 publications

References 38 publications

New‐onset primary Sjögren's syndrome following exposure to severe acute respiratory syndrome coronavirus 2: A retrospective cohort study

New‐onset primary Sjögren's syndrome following exposure to severe acute respiratory syndrome coronavirus 2: A retrospective cohort study

Evaluation of early retinal changes in patients on long-term hydroxychloroquine using optical coherence tomography angiography

Avaliação dos níveis sanguíneos de hidroxicloroquina em pacientes com doença de Sjögren: adesão à medicação e correlações clínicas

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