Objective: To describe data on the safety and efficacy of molnupiravir (MP) and nirmatrelvir/ritonavir (NM/R) in patients with systemic autoimmune rheumatic diseases (SARDs).Methods: Among patients with SARD being followed in 2 tertiary outpatient rheumatology clinics, we retrospectively identified those infected with SARS-CoV-2 between February and August 2022 who received MP or NM/R. Patients’ medical files were reviewed for demographics and disease-related characteristics, as well as coronavirus disease (COVID-19) characteristics, including vaccination status, antiviral treatment, side effects, and COVID-19 outcomes.Results: Seventy-four patients with SARD (52 females) were identified who had been infected with SARS-CoV-2 and received MP (n = 26, 35.1%) or NM/R (n = 48, 64.9%). Most patients were vaccinated against SARS-CoV-2 (n = 62, 83.8%). Among frequently used regimens were glucocorticoids (n = 43, 58.1%), mycophenolate mofetil (n = 26, 35.1%), tumor necrosis factor inhibitors (n = 14, 18.9%), methotrexate (n = 13, 17.6%), and rituximab (n = 12, 16.2%). Common adverse events were reported only by 4 patients receiving NM/R (metallic taste, gastrointestinal upset, hypertension), not leading to drug discontinuation. During follow-up, all but 2 patients (n = 72, 97.3%) recovered at home without COVID-19–related complications. Nonetheless, we describe 2 presumptive cases of COVID-19 rebound who progressed to severe COVID-19.Conclusion: These data show a favorable outcome and acceptable safety profile of the 2 oral antiviral therapies MP and NM/R among a high-risk SARD population. However, cases of COVID-19 rebound are being increasingly identified. These findings call for continuous surveillance to capture the real-world efficacy and safety profiles in our subpopulations of interest.

Immune-mediated necrotizing myopathy (IMNM), a type of inflammatory myopathy, is associated with anti-SRP or anti-3-hydroxy-3-methylglutaryl coenzyme A reductase (anti-HMGCR) antibodies, with statin use potentially inducing statin-associated IMNM (SAIMNM) due to HMGCR targeting. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors may offer a safer alternative for lipid-lowering in these patients. This study aims to describe the clinical characteristics of SAIMNM patients and evaluate the safety of PCSK9 inhibitors after myositis onset. We present the clinical characteristics of five SAIMNM patients and evaluate the safety of PCSK9 inhibitors in these cases. Additionally, we conducted a literature review using four different databases (Medline/PubMed, Scopus, Cochrane and DOAJ) to summarize the available data on IMNM. While numerous articles discussed statin-induced myositis, we selected only those studies that addressed the treatment of dyslipidemia after the management of IMNM. All five patients were women, with four having a history of statin use. One statin-naïve patient was positive for anti-SRP antibodies, while the others had anti-HMGCR antibodies. After a mean follow-up of 18.2 months, creatine phosphokinase (CPK) levels dropped from 1028.6 IU/L to 135 IU/L, and LDL cholesterol levels decreased from 206.2 mg/dL to 87.2 mg/dL. All patients were treated with steroids (with a gradual dosage reduction), and four of the five received second line immunosuppressive therapy, such as intravenous immunoglobulin, methotrexate, azathioprine, and mycophenolate mofetil. No disease recurrence occurred after starting PCSK9 inhibitors. A review of seven studies (15 patients) showed a mean CPK of 1531.9 IU/L. 40% received steroids and another immunosuppressant. Statin rechallenge caused relapse in two cases, but PCSK9 inhibitors were well tolerated, with only one patient needing additional immunosuppression. Additionally, ezetimibe and bempedoic acid were used successfully in some patients. Finally, lipid levels appeared to be lower after treatment with PCSK9 inhibitors. Administration of PCSK9 inhibitors appears to be an effective and safe option for the treatment of dyslipidaemia in patients with IMNM.

Objectives: Systemic sclerosis (SSc) is a rare and complex autoimmune disease with significant complications. During the past few years, research interest has focused on the differences between female and male patients. However, there is a lack of data regarding the role of sex in the presence of small airway disease (SAD). Therefore, we aimed to investigate the impact of sex on pulmonary involvement in a cohort of SSc patients, focusing primarily on small airways. Methods: For this retrospective study, consecutive patients with a diagnosis of SSc that visited our department up to January 2024 were recruited. Demographic data, disease manifestations, serological profile and internal organ involvement were compared between the two groups. Results: In total, 393 patients (female-to-male ratio 6:1) were included. Median time to diagnosis after the onset of Raynaud’s was significantly longer for female patients. Electrocardiogram abnormalities were more common in male patients, while telangiectasias, calcinosis and arthralgias were more common in female individuals. Moreover, male SSc patients exhibited a higher prevalence of ILD and shorter time until the diagnosis of ILD. However, female individuals demonstrated a lower maximal-mid expiratory flow rate (MMEF) and higher ratio of residual volume to total lung capacity. Interestingly, sex remained an independent predictor of MMEF, in the multivariate analysis. Conclusion: Our results showed that, although ILD is more common in male SSc patients, SAD was more prevalent among female individuals. Importantly, female sex remained an independent predictor of SAD. This study further supports the presence of sex-related differences in SSc, with important implications in disease course and management.

Background Systemic Sclerosis (SSc) is a connective tissue disease affecting multiple systems, including the respiratory and cardiovascular systems. Among the various disease complications, interstitial lung disease (ILD), pulmonary arterial hypertension (PAH) and -lately recognized- myocardial fibrosis (MF), are those mainly related to reduced life expectancy. Objectives We aimed to evaluate the prevalence of SSc complications and to investigate possible associations with patients’ clinical and serological characteristics. Methods Patients fulfilling the ACR/EULAR 2013 Scleroderma criteria, who were followed at our tertiary rheumatology centre between January 2018 and December 2022, were included in our cohort. Demographic, clinical, and serological characteristics, as well as imaging data (high-resolution chest CT, cardiac MRI) were used in our retrospective analysis. Results Ninety-one patients were included in our study, with 39.6% of them having diffuse cutaneous SSc. Most patients were female (81.3%), with a mean age at diagnosis 50.3 ±14.5 years and a mean disease duration 10.2 ±9.0 years. Leaving aside Raynaud’s phenomenon and sclerodactyly, gastrointestinal involvement (71.4%), ulcers (46.2%) and arthritis (45.1%) were among the most prevalent clinical manifestations. Mean baseline FEV1 and FVC values were normal (83.4%±16.8 and 84.4%±18.5 respectively, while mean baseline DLCO was pathological (62.6±18.9). All patients underwent a high-resolution CT early at diagnosis and upon rheumatologist’s/pulmonologist’s judgement afterwards. Eighty-one patients (89.0%) were diagnosed with interstitial lung disease (76.0% had NSIP pattern, 24.0% UIP pattern). Patients with NSIP had better scores in lung function tests than those with UIP pattern (Mean difference in FEV1, FVC and DLCO were 13,3%, 17,7%, and 12% respectively, p<0.05 for all comparisons). Positivity for anti-topoisomerase antibody (Scl-70) presented an OR=24.9 (p=0.001) for ILD, while ACA and anti-CENP-B were negatively associated (OR=0.114, p=0.003 and OR=0.164, p=0.024, respectively). Pulmonary hypertension based on echocardiogram findings was reported in 18/91 patients (19,8%), however PAH based on right heart catheterization (RHC) was confirmed in 11 of them (12,1% of total patients). Anti-Ro52 positivity was associated with PH (OR=4.45, p=0,005) and PH-ILD coexistence (OR=5.18, p=0,002), however no association was found for ILD presence in this cohort. There was also a trend for PAH-RHC, but it did not reach statistical significance. Cardiac MRI was performed in 24 patients, and non-ischemic myocardial fibrosis (compatible with SSc involvement) was identified in 18/24. The mean disease duration in MF group was longer (8.7 ±7.3 vs 3.3 ±4.3, p=0.040). Gastrointestinal involvement seems to confer an increased risk for this complication (OR=10.0, p=0.038). Conclusion The estimated ILD prevalence in our study is significantly higher than the one reported in the literature. As a referral centre, the patients reaching to our department probably have worse organ involvement than the average patient of primacy care setting. In addition, universal screening with a baseline HRCT and close monitoring lead to an earlier identification of this population. Anti-Ro52 has been recently reported as an independent risk factor for PAH. Our results could not verify this observation, probably due to the relatively small number of PAH patients in our study. Cardiac MRI availability and radiologist’s experience are essential for MF diagnosis. It is our belief that larger studies are necessary to evaluate this population. References [1]Khanna SA, Nance JW, Suliman SA. Detection and Monitoring of Interstitial Lung Disease in Patients with Systemic Sclerosis. Curr Rheumatol Rep. 2022 May;24(5):166-173. [2]AYS Lee, KA Patterson et al (2021) Anti-Ro52/TRIM21 is independently associated with pulmonary arterial hypertension and mortality in a cohort of systemic sclerosis patients, Scand J Rheumatol, 50:6, 469-474. Acknowledgements: NIL. Disclosure of Interests None Declared.