ABSTRACT
Systemic lupus erythematosus (SLE) is a chronic multisystem auto-immune disease with extremely varied clinical manifestations and a complex pathogenesis. New insights in SLE about pathogenetic pathways, biomarkers, and data on clinical manifestations are progressively emerging, and new drugs and new therapeutic strategies have been proposed to improve the control of disease activity. Thus, this review is aimed to summarise the most relevant data about SLE emerged during 2021, following the previous annual review of this series. © Copyright Clinical and Experimental Rheumatology 2022.
ABSTRACT
Background: Management of the health emergency caused by COVID-19 pandemic majorly disrupted the delivery of healthcare services to patients with chronic conditions like Systemic Autoimmune Diseases (SAD), both because resources were mainly channeled towards the care of infected patients, but also because patients tended to avoid seeking medical care for fear of becoming infected. PER-MAS is a 2-year project aimed at assessing the clinical, psychopathological, and socio-economic impact of COVID-19 in a cohort of patients with SAD. Objectives: To assess the impact of COVID-19 pandemic on drug withdrawal, disease fares and hospitalizations for disease exacerbation in a cohort of patients with SAD through an interim analysis of data from the PER-MAS project. Methods: A sample of 214 consecutive patients was recruited in a reference center for rare and complex autoimmune diseases from April 2021 to January 2022. Inclusion criteria were definite diagnosis of SAD (Connective Tissue Disease (CTD), Inflammatory Arthritis (IA) or Vasculitis), regular follow-up and at least 2 years of disease. Patients were asked to fill out an extensive self-administered questionnaire on disease activity and healthcare resource use during the pandemic (March 2020-moment of assessment). Pre-pandemic (March 2019-February 2020) and early pandemic (March 2020-February 2021) clinical data were recorded through retrospective chart review and patient interview. Results: At enrolment, 119 patients were affected by CTDs (55.6%), 71 by IA (33.18%), 24 by vasculitis (11.21%), with mean age 50.44± 12.97, and mean disease duration 11.17 ± 8.94. 30.37% took steroids, 39.7% hydroxy-chloroquine, 61.68% DMARDs, and 9.3% vasoactive drugs. Overall, disease course was similar in pre-pandemic and early pandemic phase: in the first period, rheumatologic condition was stable in 57.35% of patients, persistently active in 27.3% and 35.61% had ≥ 1 episode of disease exacerbation (mean 0.665±1.15, range 0-6);in the second period, 60.56% of patients was stable, 24.88% persistently active, and 39.44% had ≥1 exacerbation (mean 0.49 ±0.77, range 0-4). Mean number of visits (2.56±2.57 and 2.61±2.79), hos-pitalizations (0.168±0.698 and 0.14±0.473, p=0.6), number of patients with outpatient visits=0 (7.47 vs 7%), and number of patients with ≥ 1 hospital admission (10.28 vs 11.6%) were also similar, while the number of patients with hospital admissions for disease exacerbation was significantly higher in the second period (6.1 vs 11.21%, p=0.001). 170 patients completed the survey: from March 2020 to enrolment, 18.2% suspended ≥1 anti-rheumatic drug (6.25% of them for fear of contracting COVID-19 disease, 15.6% for difficulty in obtaining medications), 20% self-managed ≥ 1 disease exacerbation, and 40% had ≥ 1 telemedicine consult. From March to July 2020, 41.76% had their visit rescheduled (35.23% for hospital access restrictions, 5.3% for travel restrictions, 1.17% for fear). Conversely, only 14.7% of patients had their visit rescheduled (8.23% for hospital access restrictions, 4.7% for other reasons) from July 2020 to enrolment. Conclusion: In the early pandemic phase, overall disease course was similar to the pre-pandemic phase, but we observed an increase in the number of patients with ≥ 1 hospitalization for disease. Moreover, despite our efforts, patients reported a non-negligible rate of drug discontinuation for non-medical indication and difficulty to get access to rheumatologic consultation, highlighting the need of alternative organizational models in case of future pandemics.
ABSTRACT
Background: Growing evidence from in vitro and clinical studies have highlighted important similarities between severe COVID-19 and rapidly progressive interstitial lung diseases (ILD) occurring in systemic autoimmune disorders. These data supported the use of anti-rheumatic drugs, baricitinib and glucocor-ticoids, for the treatment of COVID-19 pneumonia. Objectives: To compare mortality rate and infammatory response in critically ill COVID-19 patients treated with either a 'rheumatologic approach' based on baricitinib plus pulse steroids (BPS) or with a 'conventional approach' (Standard of Care, SoC). Methods: In this retrospective study, we enrolled patients admitted to the Intensive Care Unit (ICU) with CT-proven SARS-CoV2 pneumonia, from September 2020 to April 2021. Demographic, laboratory, and clinical data were collected at the admission to ICU and after one week of treatment. SoC included dexameth-asone 6 to 8 mg daily plus remdesivir (+/-antibiotics and hydroxychloroquine);BPS approach was based on baricitinib 4 mg daily for 10-14 days plus 6-methyl-prednisolone pulses (250-500 mg) for three consecutive days followed by rapid tapering. The primary endpoint was the intra-ICU mortality rate;the secondary endpoint was the change in infammatory biomarkers at week 1 after treatment. Results: We enrolled a total of 210 consecutive patients with SARS-CoV2 pneumonia (male 61.4%, mean age 66.6 ± 10.9 years);137/210 (male 59.8%, mean age 66.3 ± 11.9 years) were treated with SoC and 73/210 (male 64.3%, mean age 67.3 ± 8.8 years) with BPS. At admission in ICU, all patients presented lag time from the frst symptom of SARS-CoV2 infection ≤ 10 days, laboratory biomarkers' alterations suggestive of hyper-infammatory response (CRP 10.8 ± 11.9 mg/dL, ferritin 1238 ± 1005 μ g/L, fbrinogen 575 ± 173 mg/dL, LDH 385 ± 152 U/L) and severe respiratory failure, requiring non-invasive or invasive ventilatory support. Lung-CT pattern showed multiple and diffuse areas of ground glass opacities, septal thickening, and/or consolidation. No statistically signifcant differences were found between SoC and BPS groups in terms of demographic, laboratory, and clinical features at enrolment. 59/210 (28.1%) patients died during ICU hospitalization (mean ICU length of stay 14.6 ± 9.6 days). Mortality rate in the BPS group (13/73, 17.8%) resulted signifcantly lower compared to that in the SoC group (46/137, 33.6%) (p= 0.016). Furthermore, patients in the BPS group had signifcantly lower levels of CRP (BPS=1.9 ± 2.8 vs SoC 6.1 ± 7.3, p<0.001) and fbrinogen (BPS=335 ± 108 vs SoC 453 ± 172, p<0.001) at one week after the start of treatment. Conclusion: Our real-life experience, in an ICU setting, showed that baricitinib and pulse steroids combination was associated with a lower mortality rate paralleled by a prompt reduction of infammatory biomarkers. These results shed new light on the possible usefulness of baricitinib for the treatment of rapidly progressive ILD in patients with systemic autoimmunity and hyper-infammation.
ABSTRACT
Background: Fatigue in SLE has a multifactorial origin and disease activity seems to contribute only minimally to its genesis. Therefore, non-pharmacological therapeutic strategies should also be considered in the management of fatigue. There is some evidence on the effectiveness of aerobic exercise programs in improving fatigue, without a negative impact on disease manifestations. Objectives: the aim of this study was to analyze fatigue and Health Related Quality of Life (HRQoL) in a monocentric cohort of patients with SLE, in a condition of stable remission or low disease activity, before and after a program of physical exercise, through the administration of validated Patient Reported Outcomes (PROs). Methods: this is a cross-sectional interventional study which included patients with SLE, aged between 18 and 55 years, in a condition of stable (≥12 months) remission (DORIS)1 or low disease activity (LLDAS)2. Patients enrolled had a FACIT score ≤40 in the previous 6 months. Patients with other possible causes of fatigue (e.g.: anemia, hypothyroidism, severe vitamin D defciency), active arthritis or physical disabilities were excluded. For each patient, demographics, comorbidities, treatment, clinical and laboratory data were collected. Disease activity was evaluated with the SELENA-SLEDAI and organ damage with the SLICC/DI. Each patient completed the following PROs before and after the interventional program: SF-36, FACIT-Fatigue, LIT, HADS. Due to the limitations related to the COVID-19 pandemic, the physical exercise sessions were carried out using the Google Meet digital platform. Patients were asked to participate to at least 70% of the lessons. The physical exercise program included moderate intensity aerobic exercises (muscle strengthening, joint mobility, breathing, static and dynamic stretching, balance and neuro-dynamics);workouts were performed 3 times a week, consisting of 60 minutes each. The program lasted for 12 weeks. Results: we enrolled 12 female patients, regularly followed at the Rheumatology Unit of Pisa;only 9 of them completed the study (mean age 38.56 ± 9.1 years;median disease duration 7 years (IQR 5,25-9,75)). 8/9 were in stable remission, while 1/9 was in LLDAS for the presence of leukopenia. 2/9 patients presented organ damage, one for cataract and one for renal insufficiency, while none presented damage in the musculoskeletal system. 33.3% of patients had fbromyalgia. 88.8% was on treatment with Hydroxy-chloroquine, 55.5% was on low dose steroids (2±1.9 mg/daily), 33.3% was on Mycophenolate Mofetil;only 1 patient was on Belimumab. All PROs showed a trend to improvement at the end of the 12-week program of physical activity (Table 1). We demonstrated a statistically signifcant improvement of: FACIT, LIT, depression score of the HADS and MCS of the SF-36. The items of role physical (RP), vitality (VT) and mental health (MH) of the SF-36 also showed a signifcant improvement. Conclusion: In a small cohort of SLE patients in remission but with severe fatigue, in the difficult context of COVID-19 pandemic, we demonstrated that an online program of physical exercise may determine a signifcant improvement of fatigue, perception of disease burden and mental health. In the context of a multidisciplinary management, fnding effective intervention programs to improve fatigue and HRQoL in SLE patients appears of utmost importance, with the fnal aim of improving patients' health status.