Pharmaceutical messianism and the politics of COVID-19 in the United States.

Throughout the COVID-19 pandemic, public officials in the United States - from the President to governors, mayors, lawmakers, and even school district commissioners - touted unproven treatments for COVID-19 alongside, and sometimes as opposed to, mask and vaccine mandates. Utilising the framework of 'pharmaceutical messianism', our article focuses on three such cures - hydroxychloroquine, ivermectin, and monoclonal antibodies - to explore how pharmaceuticals were mobilised within politicised pandemic discourses. Using the states of Utah, Texas, and Florida as illustrative examples, we make the case for paying attention to pharmaceutical messianism at the subnational and local levels, which can very well determine pandemic responses and outcomes in contexts such as the US where subnational governments have wide autonomy. Moreover, we argue that aside from the affordability of the treatments being studied and the heterodox knowledge claiming their efficacy, the widespread uptake of these cures was also informed by popular medical (including immunological) knowledge, pre-existing attitudes toward 'orthodox' measures like vaccines and masks, and mistrust toward authorities and institutions identified with the 'medical establishment'. Taken together, our case studies affirm the recurrent nature of pharmaceutical messianism in times of health crises - while also refining the concept and exposing its limitations.

Association of systemic lupus erythematosus standard of care immunosuppressants with glucocorticoid use and disease outcomes: a multicentre cohort study.

BACKGROUND: This study examines the association of standard-of-care systemic lupus erythematosus (SLE) medications with key outcomes such as low disease activity attainment, flares, damage accrual, and steroid-sparing, for which there is current paucity of data. METHODS: The Asia Pacific Lupus Collaboration (APLC) prospectively collects data across numerous sites regarding demographic and disease characteristics, medication use, and lupus outcomes. Using propensity score methods and panel logistic regression models, we determined the association between lupus medications and outcomes. RESULTS: Among 1707 patients followed over 12,689 visits for a median of 2.19 years, 1332 (78.03%) patients achieved the Lupus Low Disease Activity State (LLDAS), 976 (57.18%) experienced flares, and on most visits patients were taking an anti-malarial (69.86%) or immunosuppressive drug (76.37%). Prednisolone, hydroxychloroquine and azathioprine were utilised with similar frequency across all organ domains; methotrexate for musculoskeletal activity. There were differences in medication utilisation between countries, with hydroxychloroquine less frequently, and calcineurin inhibitors more frequently, used in Japan. More patients taking leflunomide, methotrexate, chloroquine/hydroxychloroquine, azathioprine, and mycophenolate mofetil/mycophenolic acid were taking ≤ 7.5 mg/day of prednisolone (compared to > 7.5 mg/day) suggesting a steroid-sparing effect. Patients taking tacrolimus were more likely (Odds Ratio [95% Confidence Interval] 13.58 [2.23-82.78], p = 0.005) to attain LLDAS. Patients taking azathioprine (OR 0.67 [0.53-0.86], p = 0.001) and methotrexate (OR 0.68 [0.47-0.98], p = 0.038) were less likely to attain LLDAS. Patients taking mycophenolate mofetil were less likely to experience a flare (OR 0.79 [0.64-0.97], p = 0.025). None of the drugs was associated with a reduction in damage accrual. CONCLUSIONS: This study suggests a steroid-sparing benefit for most commonly used standard of care immunosuppressants used in SLE treatment, some of which were associated with an increased likelihood of attaining LLDAS, or reduced incidence of flares. It also highlights the unmet need for effective treatments in lupus.

Hydroxychloroquine-Induced Nonthrombocytopenic Purpura: A Case Series.

Hydroxychloroquine (HCQ) is a disease-modifying anti-rheumatic medication for the treatment of various autoimmune conditions. A rare side effect of HCQ is thrombotic thrombocytopenic purpura (TTP). We present two cases of patients who developed purpura that did not meet TTP criteria following treatment with HCQ. While the etiology of HCQ-associated TTP is poorly understood, we propose a spectrum of manifestations related to HCQ, ranging from benign purpura to TTP. As multiple factors contribute to the disease, we believe that HCQ may act as a "second hit" in patients with genetic susceptibility, which also influences the variability in the severity of disease manifestations. J Drugs Dermatol. 2024;23(5):e124.     doi:10.36849/JDD.7781e.

Risk Factors for Hydroxychloroquine Retinopathy and Its Subtypes.

Importance: The major toxic effect of hydroxychloroquine is retinopathy. Thus, current guidelines recommend limiting the dose and screening annually for retinopathy among all long-term users, but individual patient factors may be associated with retinopathy risk. Objective: To identify risk factors beyond hydroxychloroquine dose and duration of use for hydroxychloroquine retinopathy. Design, Setting, and Participants: This cohort study of 4677 patients in the Kaiser Permanente Northern California integrated health network who initiated hydroxychloroquine, continued treatment, and underwent retinopathy screening after 5 years of use was conducted from July 1, 1997, to December 31, 2020, with up to 15 years of follow-up. Statistical analysis was performed in August 2023. Exposure: Candidate risk factors included age at hydroxychloroquine initiation, sex, race and ethnicity, indications, chronic kidney disease (CKD), liver disease, diabetes, tamoxifen use, and medications that interact with hydroxychloroquine metabolism. Hydroxychloroquine dose was assessed from pharmacy dispensing records. Main Outcome and Measures: Incident hydroxychloroquine retinopathy was adjudicated from masked review of guideline-recommended screening studies and classified as parafoveal or pericentral pattern. Multivariable Cox proportional hazards regression was used to assess potential risk factors for hydroxychloroquine retinopathy within 15 years of initiation. Results: Of 4677 long-term hydroxychloroquine users (mean [SD] age at initiation, 52.4 [14.1] years; 3877 women [82.9%]), 125 patients developed hydroxychloroquine retinopathy within 15 years (102 parafoveal, 23 pericentral). Older age at time of hydroxychloroquine initiation was associated with retinopathy risk, with adjusted hazard ratios (HRs) of 2.48 (95% CI, 1.28-4.78) for those aged 45 to 54 years, 3.82 (95% CI, 2.05-7.14) for those aged 55 to 64 years, and 5.68 (95% CI, 2.99-10.79) for those aged 65 years or older compared with those younger than 45 years. The risk of retinopathy was higher among females than males (HR, 3.83 [95% CI, 1.86-7.89]), among patients with CKD stage 3 or greater (HR, 1.95 [95% CI, 1.25-3.04]), and among individuals with tamoxifen use (HR, 3.43 [95% CI, 1.08-10.89]). The likelihood of pericentral retinopathy was higher among Asian patients (HR, 15.02 [95% CI, 4.82-46.87]) and Black patients (HR, 5.51 [95% CI, 1.22-24.97]) compared with non-Hispanic White patients. Conclusions and Relevance: This study suggests that increasing age, female sex, CKD stage 3 or greater, and tamoxifen use were associated with a higher risk of hydroxychloroquine retinopathy, whereas being younger than 45 years at hydroxychloroquine initiation and male sex were associated with a lower risk. Race and ethnicity were also associated with the pattern of retinopathy. These factors should be incorporated into hydroxychloroquine dosing decisions.

Utility of hydroxychloroquine laboratory monitoring in dermatologic and rheumatologic patients.

Hydroxychloroquine (HCQ) is an immunomodulator used in dermatology and rheumatology. Side effects may be observed on routine monitoring studies before they become clinically apparent. The goal of this retrospective chart review was to assess laboratory abnormalities in dermatologic and rheumatologic patients taking HCQ. Medical records of patients prescribed HCQ were retrospectively reviewed. Demographics, reported side effects, and parameters on baseline and follow-up complete blood count (CBC) and comprehensive metabolic panel (CMP) were recorded and graded. Laboratory abnormalities were considered severe if they were grade 3 or greater according to Common Terminology Criteria for Adverse Events v3.0 and persistent if they continued beyond subsequent laboratory testing. Of 646 eligible charts, 289 had monitoring studies for review. There were 35 severe (grade 3 or 4, 35/289; 12%) adverse events that developed, as noted on CBC or CMP. Of these 35 severe adverse events, 25 self-corrected on subsequent testing, and 10 (10/289, 3%) across 9 patients were persistent, including glomerular filtration rate, alanine transferase, alkaline phosphatase, glucose, hemoglobin and lymphopenia abnormalities. Of these 10 abnormalities, 7/10 (70%) were unlikely due to hydroxychloroquine use according to the calculated Naranjo score for each patient. Severe laboratory abnormalities while taking hydroxychloroquine are rare, even in a population with a high rate of comorbidities. Among the abnormalities observed, the majority of them (70%) were likely due to disease progression or a medication other than hydroxychloroquine. CBC and CMP monitoring for the reason of observing abnormalities while on HCQ should be at the discretion of the prescribing physician.

From Androgen Dependence to Independence in Prostate Cancer: Unraveling Therapeutic Potential and Proteomic Landscape of Hydroxychloroquine as an Autophagy Inhibitor.

Prostate cancer is a major planetary health challenge wherein new ways of thinking drug discovery and therapeutics innovation are much needed. Numerous studies have shown that autophagy inhibition holds a significant role as an adjunctive intervention in prostate cancer. Hydroxychloroquine (HCQ) has gained considerable attention due to its established role as an autophagy inhibitor across diverse cancer types, but its proteomics landscape and systems biology in prostate cancer are currently lacking in the literature. This study reports the proteomic responses to HCQ in prostate cancer cells, namely, androgen-dependent LNCaP and androgen-independent PC3 cells. Differentially expressed proteins and proteome in HCQ-treated cells were determined by label-free quantification with nano-high-performance liquid chromatography and tandem mass spectrometry (nHPLC-MS/MS), and harnessing bioinformatics tools. In PC3 cells, there was a marked shift toward metabolic reprogramming, highlighted by an upregulation of mitochondrial proteins in oxidative phosphorylation and tricarboxylic acid cycle, suggesting an adaptive mechanism to maintain energy production under therapeutic stress. In contrast, LNCaP cells prioritized proteostasis and cell cycle regulation, indicating a more conservative adaptation strategy. To the best of our knowledge, this study is the first to demonstrate the differential responses of prostate cancer cells to autophagy inhibition by HCQ, suggesting that a combination therapy approach, targeting distinct pathways in androgen-independent and androgen-dependent cells, could represent a promising treatment strategy. Moreover, the varied proteomic responses observed between these cell lines underscore the importance of personalized medicine in cancer therapy. Future translational and clinical research on HCQ and prostate cancer are called for.

Exogenous Metabolic Modulators Improve Response to Carboplatin in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) lacks targeted therapies, leaving cytotoxic chemotherapy as the current standard treatment. However, chemotherapy resistance remains a major clinical challenge. Increased insulin-like growth factor 1 signaling can potently blunt chemotherapy response, and lysosomal processes including the nutrient scavenging pathway autophagy can enable cancer cells to evade chemotherapy-mediated cell death. Thus, we tested whether inhibition of insulin receptor/insulin-like growth factor 1 receptor with the drug BMS-754807 and/or lysosomal disruption with hydroxychloroquine (HCQ) could sensitize TNBC cells to the chemotherapy drug carboplatin. Using in vitro studies in multiple TNBC cell lines, in concert with in vivo studies employing a murine syngeneic orthotopic transplant model of TNBC, we show that BMS-754807 and HCQ each sensitized TNBC cells and tumors to carboplatin and reveal that exogenous metabolic modulators may work synergistically with carboplatin as indicated by Bliss analysis. Additionally, we demonstrate the lack of overt in vivo toxicity with our combination regimens and, therefore, propose that metabolic targeting of TNBC may be a safe and effective strategy to increase sensitivity to chemotherapy. Thus, we conclude that the use of exogenous metabolic modulators, such as BMS-754807 or HCQ, in combination with chemotherapy warrants additional study as a strategy to improve therapeutic responses in women with TNBC.

New methods for resolution of hydroxychloroquine by forming diastereomeric salt and adding chiral mobile phase agent on RP-HPLC.

Hydroxychloroquine (HCQ), 2-([4-([7-Chloro-4-quinolyl]amino)pentyl]ethylamino)ethanol, exhibited significant biological activity, while its side effects cannot be overlooked. The RP-HPLC enantio-separation was investigated for cost-effective and convenient optical purity analysis of HCQ. The thermodynamic resolution of Rac-HCQ, driven by enthalpy and entropy, was achieved on the C18 column using Carboxymethyl-ß-cyclodextrin (CM-ß-CD) as the chiral mobile phase agent (CMPA). The effects of CCM-ß-CD, pH, and triethylamine (TEA) V% on the enantio-separation process were explored. Under the optimum conditions at 24°C, the retention times for the two enantiomers were t R 1 = 29.39 min $$ {t}_{R1}=29.39\ \min $$ and t R 2 = 32.42 min $$ {t}_{R2}=32.42\ \min $$ , resulting in R s = 1.87 $$ {R}_s=1.87 $$ . The resolution via diastereomeric salt formation of Rac-HCQ was developed to obtain the active pharmaceutical ingredient of single enantiomer S-HCQ. Di-p-Anisoyl-L-Tartaric Acid (L-DATA) was proved effective as the resolution agent for Rac-HCQ. Surprisingly, it was found that refluxing time was a key fact affecting the resolution efficiency, which meant the kinetic dominate during the process of the resolution. Four factors-solvent volume, refluxing time, filtration temperature, and molar ratio-were optimized using the single-factor method and the response surface method. Two cubic models were established, and the reliability was subsequently verified. Under the optimal conditions, the less soluble salt of 2L-DATA:S-HCQ was obtained with a yield of 96.9% and optical purity of 63.0%. The optical purity of this less soluble salt increases to 99.0% with a yield of 74.2% after three rounds recrystallization.

A crossover study to evaluate the pharmacokinetics and bioequivalence of hydroxychloroquine tablets in healthy Chinese subjects.

AIMS: Hydroxychloroquine (HCQ) has a high variability and a long half-life in the human body. The purpose of this study was to evaluate the bioequivalence of a generic HCQ tablet (test preparation) versus a brand HCQ tablet (reference preparation) under fasting and fed conditions in a crossover design. MATERIALS AND METHODS: This was an open-label, two-period randomized, single-dose, crossover study in 47 healthy Chinese subjects who were sequentially and randomly allocated either to the fed group (high-fat meal; n = 23) or the fasting group (n = 24). Participants in each group were randomized to the two arms to receive either a single 200-mg dose of the test preparation or a 200-mg dose of the reference preparation. The application of the two preparations in each patient was separated by a 28-day washout period, regarded as sufficiently long to avoid significant interference from residual drug in the body. Whole blood samples were collected over 72 hours after drug administration. RESULTS: A total of 23 subjects completed both the fed and the fasting parts of the trial. There were no significant differences in Cmax, AUC0-72h, and T1/2 between the test and reference preparation (p < 0.05). Food had no significant effect on Cmax and T1/2 (p < 0.05), but AUC0-72h values were significantly reduced under fed condition compared to fasting condition (p < 0.05). The 90% confidence intervals (CIs) for the geometric mean ratios (GMRs) of Cmax and AUC0-72h were 0.84 - 1.05 and 0.89 - 0.98 in the fed study, and 0.97 - 1.07 and 0.97 - 1.05 in the fasting study, respectively. The carryover effect due to non-zero blood concentrations resulted in higher AUC0-72h values in the second period for both test and reference formulations and had no effect on the statistical results. No serious adverse events were reported. CONCLUSION: The investigation demonstrated that the test and reference preparations are bioequivalent and well tolerated under both fasting and fed conditions in healthy Chinese subjects.

Effect of hydroxychloroquine blood concentration on the efficacy and ocular toxicity of systemic lupus erythematosus.

In the absence of evidence-based guidance on the impact of hydroxychloroquine (HCQ) blood concentration on efficacy and ocular toxicity in systemic lupus erythematosus (SLE), the clinical monitoring of HCQ blood concentration is not yet widely performed, which raised concerns about the necessity of conducting HCQ blood concentration monitoring. In this retrospective study, we consecutively enrolled 135 patients with SLE who received HCQ treatment for more than 6 months from July 2022 to December 2022. Ocular toxicity was evaluated by collecting relevant retinal parameters using optical coherence tomography angiography (OCTA). Therapeutic efficacy was evaluated using the SLE disease activity index (SLEDAI) and relevant clinical parameters. HCQ blood concentration was determined by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Spearman correlation analysis revealed that the cumulative dose of HCQ was positively correlated with the foveal avascular zone (FAZ) perimeter and FAZ area (r = 0.734, P < 0.001; r = 0.784, P < 0.001). Meanwhile, the treatment duration of HCQ was positively correlated with FAZ perimeter and FAZ area (r = 0.761, P < 0.001; r = 0.882, P < 0.001). The univariate and multivariate logistic regression analyses indicated that HCQ blood concentration was associated with the disease activity of patients with SLE (odds ratio 0.994, 95% CI 0.990-0.999). HCQ blood concentration may be an important factor in assessing the therapeutic effectiveness of SLE patients. The HCQ-related ocular toxicity was a long-term effect related to long term exposure, rather than the blood concentration of HCQ at the time of testing. More importantly, when addressing HCQ-related ocular toxicity, it may be crucial to pay attention to the cumulative dose and treatment duration of HCQ.

A case report of Vancomycin in the treatment of Q fever endocarditis.

The patient, a 43-year-old male, was admitted to the hospital with gradually aggravated exertional palpitations and chest tightness over a 2-day period. Upon hospital admission, a cardiac ultrasound revealed aortic valve redundancy, however multiple blood culture investigations came back negative. Blood mNGS was perfected, revealing Coxiella burnetii, and the diagnosis of Q fever (query fever) was established. The temperature and inflammatory indices of the patient were all normal with the treatment of vancomycin before cardiac surgery. But for the potential liver damage of and the Coxiella burnetii was still positive in the anti-phase II IgG titer, the doxycycline and hydroxychloroquine instead of vancomycin were applied for the patient. Despite receiving standardized anti-infective therapy of doxycycline combined with hydroxychloroquine, this patient had fever and increased leukocytes following surgery. After the addition of vancomycin as an anti-infective treatment, the temperature and leukocytes improved quickly. During the treatment of vancomycin, a discovery of liver injury may have resulted. These findings provide new therapy options for future professionals.

An observational study to identify causative factors for not using hydroxychloroquine in systemic lupus erythematosus.

Hydroxychloroquine (HCQ) use is indicated for patients with systemic lupus erythematosus (SLE). Nevertheless, reports discussing the reasons for not prescribing HCQ are limited. We identified the factors that interfere with HCQ use in patients with SLE. This observational, single-center study included data from 265 patients with SLE in 2019. The patients were categorized into groups with and without a history of HCQ use. Between these groups, clinical characteristics were compared using univariate analysis and logistic regression models. Among the 265 patients, 133 (50.2%) had a history of HCQ use. Univariate analysis identified older age; longer disease duration; lower prednisolone dose, clinical SLE disease activity index 2000, and estimated glomerular filtration rate; higher C3 level; and lower anti-double-stranded DNA antibody concentration as HCQ non-use-related variables. Logistic regression models identified a positive association between HCQ non-use and longer disease duration (odds ratio [OR] 1.08), prednisolone dose ≤ 7.5 mg/day (OR 4.03), C3 level ≥ 73 mg/dL (OR 2.15), and attending physician having graduated > 10 years prior (OR 3.19). In conclusion, a longer disease duration, lower prednisolone dose, higher C3 level, and longer time since attending physicians' graduation correlated with HCQ non-use. Physicians and patients should be educated to facilitate HCQ use despite these factors.

Influence of the COVID-19 Pandemic on Medical Management and on Healthcare Delivery of Immune-Mediated Rheumatic and Musculoskeletal Diseases during the First Pandemic Period February to July 2020: A Systematic Review.

(1) Background and Objectives: The COVID-19 pandemic influenced the management of patients with immune-mediated rheumatic and musculoskeletal diseases (imRMDs) in various ways. The goal of our systematic review was to determine the influence of the first period of the COVID-19 pandemic (February 2020 to July 2020) on the management of imRMDs regarding the availability of drugs, adherence to therapy and therapy changes and on healthcare delivery. (2) Materials and Methods: We conducted a systematic literature search of PubMed, Cochrane and Embase databases (carried out 20-26 October 2021), including studies with adult patients, on the influence of the COVID-19 pandemic on the management of imRMDs. There were no restrictions regarding to study design except for systematic reviews and case reports that were excluded as well as articles on the disease outcomes in case of SARS-CoV-2 infection. Two reviewers screened the studies for inclusion, and in case of disagreement, a consensus was reached after discussion. (3) Results: A total of 5969 potentially relevant studies were found, and after title, abstract and full-text screening, 34 studies were included with data from 182,746 patients and 2018 rheumatologists. The non-availability of drugs (the impossibility or increased difficulty to obtain a drug), e.g., hydroxychloroquine and tocilizumab, was frequent (in 16-69% of patients). Further, medication non-adherence was reported among patients with different imRMDs and between different drugs in 4-46% of patients. Changes to preexisting medication were reported in up to 33% of patients (e.g., reducing the dose of steroids or the cessation of biological disease-modifying anti-rheumatic drugs). Physical in-office consultations and laboratory testing decreased, and therefore, newly implemented remote consultations (particularly telemedicine) increased greatly, with an increase of up to 80%. (4) Conclusions: The COVID-19 pandemic influenced the management of imRMDs, especially at the beginning. The influences were wide-ranging, affecting the availability of pharmacies, adherence to medication or medication changes, avoidance of doctor visits and laboratory testing. Remote and telehealth consultations were newly implemented. These new forms of healthcare delivery should be spread and implemented worldwide to routine clinical practice to be ready for future pandemics. Every healthcare service provider treating patients with imRMDs should check with his IT provider how these new forms of visits can be used and how they are offered in daily clinical practice. Therefore, this is not only a digitalization topic but also an organization theme for hospitals or outpatient clinics.

Interpreting hydroxychloroquine blood levels for medication non-adherence: a pharmacokinetic study.

OBJECTIVE: Characterise the relationship between hydroxychloroquine (HCQ) blood levels and the number of missed doses, accounting for dosage, dose timing and the large variability in pharmacokinetics (PK) between patients. METHODS: We externally validated a published PK model and then conducted dosing simulations. We developed a virtual population of 1000 patients for each dosage across a range of body weights and PK variability. Using the model, 10 Monte Carlo simulations for each patient were conducted to derive predicted whole blood concentrations every hour over 24 hours (240 000 HCQ levels at steady state). To determine the impact of missed doses on levels, we randomly deleted a fixed proportion of doses. RESULTS: For patients receiving HCQ 400 mg daily, simulated random blood levels <200 ng/mL were exceedingly uncommon in fully adherent patients (<0.1%). In comparison, with 80% of doses missed, approximately 60% of concentrations were <200 ng/mL. However, this cut-off was highly insensitive and would miss many instances of severe non-adherence. Average levels quickly dropped to <200 ng/mL after 2-4 days of missed doses. Additionally, mean levels decreased by 29.9% between peak and trough measurements. CONCLUSIONS: We propose an algorithm to optimally interpret HCQ blood levels and approximate the number of missed doses, incorporating the impact of dosage, dose timing and pharmacokinetic variability. No single cut-off has adequate combinations of both sensitivity and specificity, and cut-offs are dependent on the degree of targeted non-adherence. Future studies should measure trough concentrations to better identify target HCQ levels for non-adherence and efficacy.

Drug repurposing-based nanoplatform via modulating autophagy to enhance chemo-phototherapy against colorectal cancer.

Multi-modal combination therapy is regarded as a promising approach to cancer treatment. Combining chemotherapy and phototherapy is an essential multi-modal combination therapy endeavor. Ivermectin (IVM) is a potent antiparasitic agent identified as having potential antitumor properties. However, the fact that it induces protective autophagy while killing tumor cells poses a challenge to its further application. IR780 iodide (IR780) is a near-infrared (NIR) dye with outstanding photothermal therapy (PTT) and photodynamic therapy (PDT) effects. However, the hydrophobicity, instability, and low tumor uptake of IR780 limit its clinical applications. Here, we have structurally modified IR780 with hydroxychloroquine, an autophagy inhibitor, to synthesize a novel compound H780. H780 and IVM can form H780-IVM nanoparticles (H-I NPs) via self-assembly. Using hyaluronic acid (HA) to modify the H-I NPs, a novel nano-delivery system HA/H780-IVM nanoparticles (HA/H-I NPs) was synthesized for chemotherapy-phototherapy of colorectal cancer (CRC). Under NIR laser irradiation, HA/H-I NPs effectively overcame the limitations of IR780 and IVM and exhibited potent cytotoxicity. In vitro and in vivo experiment results showed that HA/H-I NPs exhibited excellent anti-CRC effects. Therefore, our study provides a novel strategy for CRC treatment that could enhance chemo-phototherapy by modulating autophagy.

Management of pregnancy in autoimmune rheumatic diseases: maternal disease course, gestational and neonatal outcomes and use of medications in the prospectiveItalian P-RHEUM.it study.

OBJECTIVES: To investigate pregnancy outcomes in women with autoimmune rheumatic diseases (ARD) in the Italian prospective cohort study P-RHEUM.it. METHODS: Pregnant women with different ARD were enrolled for up to 20 gestational weeks in 29 Rheumatology Centres for 5 years (2018-2023). Maternal and infant information were collected in a web-based database. RESULTS: We analysed 866 pregnancies in 851 patients (systemic lupus erythematosus was the most represented disease, 19.6%). Maternal disease flares were observed in 135 (15.6%) pregnancies. 53 (6.1%) pregnancies were induced by assisted reproduction techniques, 61 (7%) ended in miscarriage and 11 (1.3%) underwent elective termination. Obstetrical complications occurred in 261 (30.1%) pregnancies, including 2.3% pre-eclampsia. Two cases of congenital heart block were observed out of 157 pregnancies (1.3%) with anti-Ro/SSA. Regarding treatments, 244 (28.2%) pregnancies were treated with glucocorticoids, 388 (44.8%) with hydroxychloroquine, 85 (9.8%) with conventional synthetic disease-modifying anti-rheumatic drugs and 122 (14.1%) with biological disease-modifying anti-rheumatic drugs. Live births were 794 (91.7%), mostly at term (84.9%); four perinatal deaths (0.5%) occurred. Among 790 newborns, 31 (3.9%) were small-for-gestational-age and 169 (21.4%) had perinatal complications. Exclusive maternal breast feeding was received by 404 (46.7%) neonates. The Edinburgh Postnatal Depression Scale was compiled by 414 women (52.4%); 89 (21.5%) scored positive for emotional distress. CONCLUSIONS: Multiple factors including preconception counselling and treat-to-target with pregnancy-compatible medications may have contributed to mitigate disease-related risk factors, yielding limited disease flares, good pregnancy outcomes and frequency of complications which were similar to the Italian general obstetric population. Disease-specific issues need to be further addressed to plan preventative measures.

INTRAVITREAL DEXAMETHASONE FOR THE TREATMENT OF MACULAR EDEMA SECONDARY TO HYDROXYCHLOROQUINE TOXICITY.

PURPOSE: Cystoid macular edema is a vision-threatening complication infrequently associated with hydroxychloroquine retinal toxicity. There are limited data on the best treatment for this pathology. METHODS: A retrospective case series is presented. RESULTS: In this series, we present three cases of cystoid macular edema in patients with diagnosed hydroxychloroquine maculopathy successfully treated with intravitreal dexamethasone implantation. CONCLUSION: Minimal literature has been published regarding the best management of cystoid macular edema related to hydroxychloroquine toxicity. Our case series suggests a possible new agent in the treatment of this rare occurrence.

[Low disease activity and remission status of systemic lupus erythematosus in a real-world study].

OBJECTIVE: To investigate the rates of low disease activity and clinical remission in patients with systemic lupus erythematosus (SLE) in a real-world setting, and to analyze the related factors of low disease activity and clinical remission. METHODS: One thousand patients with SLE were enrolled from 11 teaching hospitals. Demographic, clinical and laboratory data, as well as treatment regimes were collec-ted by self-completed questionnaire. The rates of low disease activity and remission were calculated based on the lupus low disease activity state (LLDAS) and definitions of remission in SLE (DORIS). Charac-teristics of patients with LLDAS and DORIS were analyzed. Multivariate Logistic regression analysis was used to evaluate the related factors of LLDAS and DORIS remission. RESULTS: 20.7% of patients met the criteria of LLDAS, while 10.4% of patients achieved remission defined by DORIS. Patients who met LLDAS or DORIS remission had significantly higher proportion of patients with high income and longer disease duration, compared with non-remission group. Moreover, the rates of anemia, creatinine elevation, increased erythrocyte sedimentation rate (ESR) and hypoalbuminemia was significantly lower in the LLDAS or DORIS group than in the non-remission group. Patients who received hydroxychloroquine for more than 12 months or immunosuppressant therapy for no less than 6 months earned higher rates of LLDAS and DORIS remission. The results of Logistic regression analysis showed that increased ESR, positive anti-dsDNA antibodies, low level of complement (C3 and C4), proteinuria, low household income were negatively related with LLDAS and DORIS remission. However, hydroxychloroquine usage for longer than 12 months were positively related with LLDAS and DORIS remission. CONCLUSION: LLDAS and DORIS remission of SLE patients remain to be improved. Treatment-to-target strategy and standar-dized application of hydroxychloroquine and immunosuppressants in SLE are recommended.