Olga Sánchez-Pernaute

Interstitial lung disease (ILD) is a major manifestation of systemic autoimmune rheumatic diseases (SARD). Unmet needs in this population are the early ide

Objectives: To evaluate whether patients with systemic lupus erythematosus (SLE) have different nailfold videocapillaroscopy (NVC) findings compared with healthy controls (HCs) and whether there is an association between NVC abnormalities and disease activity, clinical and/or laboratory features in SLE. Methods: This is an observational, multicentre, international, matched case–control study. 381 subjects (203 patients with SLE and 178 HCs) were enrolled from 16 centres in 10 countries. Clinical and laboratory data were collected using ad hoc forms. 5861 NVC images were acquired, coded and uploaded for central blinded analysis. Results: A normal NVC pattern was observed in most patients with SLE (86.6%) and, a significantly higher frequency of NVC abnormalities such as enlarged and giant capillaries, microhaemorrhages and irregular nail bed architecture (p<0.001) were found in the remaining patients. Multiple correspondence analysis outlined two NVC patterns, one of which, the more severe (cluster 2), present in 12% of patients, was characterised by a higher prevalence of lower capillary density, abnormally shaped and enlarged capillaries and irregular nail bed architecture. NVC cluster 2 had significantly higher disease activity compared with cluster 1 for both Systemic Lupus Erythematosus Disease Activity Index cut-off points ≥3 and ≥4 (p=0.016 and p=0.028, respectively). SLE with ‘more severe’ NVC pattern (cluster 2) have a significantly higher frequency of arthritis, renal involvement and ongoing glucocorticoid therapy, whereas serositis was significantly associated with ‘less severe’ NVC pattern (cluster 1). Conclusions: This study has shown that changes in NVC patterns are associated with important aspects of SLE disease activity. Future prospective studies are needed to further support the use of NVC in SLE monitoring. Trial registration number: NCT02801812.

Background: In susceptible hosts, SARS-CoV2-induced hyperinflammation accounts for an increased mortality. The search of adjuvant immunomodulatory therapies has been ongoing ever since the pandemic outbreak. Aim: Our purpose was to evaluate the efficacy of cyclosporin A (CsA) as an add-on therapy to the standard of care (SoC) in patients with severe COVID-19 pneumonia. Methods: We conducted a randomized clinical trial in patients admitted to eight Spanish tertiary hospitals. Patients were stratified into two severity categories and randomized in a 1:1 ratio to receive a corticosteroid-based standard therapy with or without CsA. The primary endpoint was FiO2 recovery by Day 12 without relapses. Results: 109 patients were included and randomized, and 98 of them considered for the mITT population (51 assigned to the CsA + SoC group and 47 to the SoC group). A total of 35 (68.6%) patients from the CsA + SoC group and 32 (71.1%) patients from the SoC group reached the primary endpoint in the mITT analysis. No differences were found after stratification into age groups, in the severity level at admission, or in a combination of both. Overall, the time to FiO2 normalization was 7.4 days vs. 7.9 days in the experimental and control groups, respectively. Global mortality was 8.2%. Severe adverse events were uncommon and equally distributed between arms. Conclusion: The addition of CsA did not show differences over a corticosteroid-based treatment in the clinical course of the included patients. A better identification of candidates who will benefit from receiving immunomodulatory drugs is necessary in future studies.

Background: In susceptible hosts, SARS-CoV2 induced hyperinflammation accounts for an increased mortality. The search of adjuvant immunomodulatory therapies has been ongoing ever since the pandemic outbreak. Aim: Our purpose was to evaluate the efficacy of cyclosporin A (CsA) as add-on therapy to standard of care in patients with severe COVID-19 pneumonia. Methods: We conducted a randomized clinical trial in patients admitted to 8 Spanish Tertiary Hospitals. Patients were stratified into two severity categories and randomized 1:1 to receive a high dose corticosteroid-based standard therapy with or without CsA. The primary endpoint was FiO2 recovery by day 12 without relapses. Results: 109 patients were included and 98 randomized: 51 of them were assigned to CsA+SoC group and 47 to Standard of Care (SoC). 96/98 of them were included in the Intention to Treat population. 35 (68.6%) patients from CsA+SoC group and 32 (71,1%) patients from SoC group reached the primary endpoint in the ITT analysis. No differences were found after stratification into age groups, severity level at admission or the combination of both. Overall, time to FiO2 normalization was 7.4 days vs 7.9 days in the experimental and control groups, respectively. Global mortality was 8.2%. Severe adverse events were uncommon and equally distributed between arms. Conclusion: Addition of CsA did not show differences over a high-dose corticosteroids-based treatment in the clinical course of included patients. A better identification of candidates who will benefit from receiving immunomodulatory drugs is necessary in future studies.

Olga Sánchez Pernaute; Voclosporin is on the table, let’s taste it, Rheumatology, , keae016, https://doi.org/10.1093/rheumatology/keae016

Objectives: To assess performance of interstitial pneumonia (IP) with autoimmune features (IPAF) criteria in clinical practice and describe the utility of additional workup in identifying patients with underlying connective tissue diseases (CTD).Methods: We set a retrospective study of our patients with autoimmune IP, who were allocated to CTD-IP, IPAF or undifferentiated autoimmune IP (uAIP) subgroups according to the updated classification criteria. Presence of the process-related variables comprising IPAF defining domains was scrutinized in all patients, and, when available, the results of nailfold videocapillaroscopy (NVC) were recorded.Results: Thirty nine out of 118 patients, accounting for 71% of former undifferentiated cases, fulfilled IPAF criteria. Arthritis and Raynaud’s phenomenon were prevalent in this subgroup. While systemic sclerosis-specific autoantibodies were restricted to CTD-IP patients, anti-tRNA synthetase antibodies were also present in IPAF. In contrast, rheumatoid factor, anti-Ro antibodies and ANA nucleolar patterns could be found in all subgroups. Usual interstitial pneumonia (UIP) / possible UIP were the most frequently observed radiographic patterns Therefore, the presence of thoracic multicompartimental findings as also performance of open lung biopsies were useful in characterizing as IPAF those UIP cases lacking a clinical domain. Interestingly, we could observe NVC abnormalities in 54% of IPAF and 36% of uAIP tested patients, even though many of them did not report Raynaud’s phenomenon.Conclusion: Besides application of IPAF criteria, distribution of IPAF defining variables along with NVC exams help identify more homogeneous phenotypic subgroups of autoimmune IP of potential relevance beyond clinical diagnosis.

Background: Idiopathic inflammatory myopathies are a heterogenous group of systemic autoimmune diseases. Several phenotypes have been linked to specific autoantibodies. Clinically amyopathic dermatomyositis with rapidly progressive interstitial lung disease, the most severe form of ILD, is associated with the anti-MDA5 antibodies. However not all the patients with dermatomyositis and anti-MDA5 positive antibodies develop this severe condition. Objectives: We aim to define different phenotypes from a large cohort of patients diagnosed with dermatomyositis who were positive to anti-MDA5 antibodies. Methods: We retrospective analyzed the clinical and immunological data of 90 anti-MDA5 patients [50 female, 55.6%, mean (SD) age at diagnosis 47 (15.4) yrs.] with dermatomyositis recruited from a multicenter register in Spain (MEDRA5) including 30 hospitals. All the patients fulfill de International Myositis Classification Criteria (EULAR/ACR) for dermatomyositis (score >90%). Anti-MDA5 were detected by means of commercial immunoblot (EUROIMMUN^©). The chi-square test was used to assess the relationships between qualitative variables. The Kruskal-Wallis test was used to compared medians between groups. Results: Sixty-six patients (73.3%) were diagnosed with clinically amyopathic dermatomyositis. Three different phenotypes linked with the anti-MDA5 antibody were identified. Group 1: patients with rapidly-ILD phenotype (28 patients, 31.1%), group 2: antisynthetase-like phenotype (23 patients, 25.5%), and group 3: non-ILD phenotype (39 patients, 43.3%). Clinical and immunological comparison between the groups disclosed that age at disease onset was higher (median, IQR) in patients from group 1 [53 (43-60)] vs. group 2 [46 (40-56)] or group 3 [42(41-51)] (p=0.01); disease onset was more frequent in spring in patients from group 1 (46.5%) than in the rest of the groups (21.7% and 28.9%) (pConclusion: Three different phenotypes of patients positive to anti-MDA5 were identified. The presence or not of ILD, or the different type (rapidly progressive or not) of ILD were the main feature that allow to differentiate these phenotypes, which are relevant in clinical practice. References: [1]Allenbach Y, Uzunhan Y, Toquet S, et al; French Myositis Network. Different phenotypes in dermatomyositis associated with anti-MDA5 antibody: Study of 121 cases. Neurology. 2020;95: e70-e78. Acknowledgements: List of contributors of MEDRA5 group: Aguilar-García J (Internal Medicine, Hospital Costa del Sol, Marbella), Carrión-Barberá I (Rheumatology, Hospital del Mar, Barcelona), Cobo-Ibañez T (Rheumatology, Hospital Infanta Sofía, San Sebastián de los Reyes), de Escalante-Yangüela B (Internal Medicine, Hospital Clínico Lozano Blesa, Zaragoza), Fonseca-Aizpuru EM (Internal Medicine, Hospital de Cabueñes, Gijón), González-Cubillo L (Intensive Medicine, Hospital Universitario de Cruces, Barakaldo), González-Gay MA (Rheumatology, Hospital Marqués de Valdecilla, Santander), Prieto-González S (Internal Medicine, Hospital Clinic, Barcelona), Ruiz-Román A (Rheumatology, Hospital Universitario Virgen del Rocío, Sevilla), Calero-Paniagua I (Internal Medicine, Hospital Virgen de la Luz, Cuenca), Callejas-Rubio JL (Internal Medicine, Hospital Clínico San Cecilio, Granada), Gil-Vila A (Internal Medicine, Hospital Vall d’Hebron, Barcelona), de Miguel-Campo B (Internal Medicine, Hospital Doce de Octubre, Madrid), García-Sevilla R (Pneumology, Hospital General Universitario de Alicante, Alicante), Iriarte-Fuster A (Internal Medicine, Hospital de Bellvitge, Hospitalet de Llobregat), Jovani-Casano V (Rheumatology, Hospital General Universitario de Alicante, Alicante), Lozano-Rivas N (Rheumatology, Hospital Virgen de la Arritxaca, Murcia), Martín-Gascón M (Internal Medicine, Hospital Morales Meseguer, Murcia), Martinez-González O (Rheumatology, Hospital Universitario de Salamanca, Salamanca), Monteagudo-Jiménez M (Internal Medicine, Hospital Parc Taulí, Sabadell), Mora-Ortega GM (Pneumology, Hospital Universitario Infanta Sofía, San Sebastián de los Reyes), Moral-Moral Pedro (Internal Medicine, Hospital Universitari i Politecnic La Fe, Valencia), Pérez-De Pedro I (Interna Medicine, Hospital Regional Universitario de Málaga, Málaga), Picazo-Talavera MR (Rheumatology, Hospital del Sureste, Madrid), Rubio-Rivas M (Internal Medicine, Hospital de Bellvitge, Hospitalet de Llobregat) Disclosure of Interests: None declared