World Lupus Day 2024
Svjetski dan lupusa 2024.
World Lupus Day is held every year on May 10th to raise awareness about this complex and often difficult-to-diagnose autoimmune disease. Early diagnosis and timely treatment are crucial for improving the quality of life of those affected. On World Lupus Day, numerous activities are organized, such as public campaigns, lectures, and humanitarian events. The goal is to educate the public about systemic lupus, provide support to those affected, and encourage research into new therapeutic options.
On May 9, 2024, the now traditional 4th Symposium was held to mark World Lupus Day, organized by the Croatian Society for Rheumatology and the Referral Center for Systemic Lupus Erythematosus and Related Diseases at the Division of Clinical Immunology and Rheumatology, Department of Internal Medicine, University Hospital Center Zagreb.
We had the opportunity to hear engaging lectures on current topics related to systemic lupus erythematosus (SLE), delivered by Prof. Miroslav Mayer, Assistant Prof. Ivan Padjen, Assistant Prof. Marija Bakula, Dr. Krešimir Rukavina and Dr. Marija Šćepović Ljucović.
The symposium was opened by Prof. Branimir Anić, Head of the Division of Clinical Immunology and Rheumatology.
After the opening remarks, Assistant Prof. Marija Bakula presented a lecture on the role of biologic agents in the treatment of SLE, focusing on rituximab, belimumab, and anifrolumab, aligned with the updated 2023 EULAR recommendations. The guidelines recognize biologic therapies as viable options for refractory disease forms. Rituximab, although not formally approved for SLE, is frequently used off-label, particularly in refractory cases. Clinical trials EXPLORER (2010) and LUNAR (2012) did not demonstrate statistically significant differences compared to placebo. Nevertheless, the LUNAR trial demonstrated encouraging improvements in proteinuria reduction and remission. Belimumab, a human monoclonal antibody targeting the BAFF cytokine, was approved for SLE in adults in 2011 and in children in 2019. It represents the first drug approved for SLE in over five decades. The BLISS-52 and BLISS-76 studies showed significant improvements in disease activity indices and reductions in relapse rates. According to the 2024 EULAR recommendations, belimumab is indicated for active SLE without central nervous system involvement or lupus nephritis, as part of combination therapy with standard treatments. Anifrolumab, a monoclonal antibody targeting the type I interferon receptor, has been approved for the treatment of SLE since 2021. Clinical trials such as TULIP-1, TULIP-2, and MUSE demonstrated its efficacy in reducing disease activity, improving skin manifestations, and lowering corticosteroid use. In post hoc analyses, anifrolumab showed superior results in reducing swollen and tender joints compared to placebo, with a favorable impact on hematological manifestations. Real-world experience confirmed rapid clinical improvements and enhanced quality of life, including reduced fatigue and improved mobility. Early introduction of anifrolumab may favorably modify disease progression and reduce glucocorticoid exposure in patients with SLE. In clinical practice, rituximab continues to be used off-label in refractory cases, especially for hematologic manifestations and lupus nephritis, while belimumab’s use is expanding to systemic manifestations and moderate disease activity. Key challenges in everyday practice include drug accessibility, costs, treatment duration, and identifying optimal candidates for biologic therapy. The development of new agents like anifrolumab, alongside the use of biomarkers and a deeper understanding of the immunopathogenesis, offers promising prospects for the future.
In a subsequent session, Assistant Prof. Ivan Padjen delivered an insightful lecture on the importance of the interferon (IFN) signature in the diagnosis and treatment of SLE. He explained the complex role of type I IFN in the pathogenesis of SLE, where genetic predisposition combined with environmental and hormonal triggers leads to chronic inflammation, immune dysregulation, and eventual tissue damage. Elevated production of cytokines, interferons, and autoantibodies characterizes the early and progressive stages of SLE, with type I IFN being a crucial driver of autoimmune activation. Dr. Padjen detailed the three types of IFN pathways, the diversity of IFN receptors across different tissues, and the pathogenic positive feedback loop initiated by type I IFN in SLE. He highlighted that IFN-driven processes are evident years before clinical disease manifests, as evidenced by elevated IFN activity and autoantibody production in preclinical stages. The presence of an “interferon gene signature” (IFNGS) has been observed in 60–80% of patients with SLE, correlating with disease activity and severity. The methods for measuring IFNGS, mostly through transcriptional profiling rather than direct measurement of IFN proteins, were discussed, noting considerable variability due to tissue-specific expression patterns and technical differences in gene selection. Assist. Prof. Padjen also presented studies showing that IFNGS levels can stratify patients by disease phenotype and may predict therapeutic responses, although the clinical utility of IFNGS still requires further validation. Importantly, anifrolumab, a monoclonal antibody targeting the type I IFN receptor, has shown significant efficacy in reducing IFNGS levels by 80–90% in high-IFNGS patients, as demonstrated in clinical trials such as TULIP-2. Nevertheless, residual IFN activity remains detectable, and the relationship between IFNGS reduction and clinical outcomes continues to be studied. The lecture concluded by emphasizing the potential role of IFNGS in patient stratification and individualized treatment planning in SLE, while cautioning that more standardized, longitudinal studies are needed to fully establish its place in clinical practice.
Dr. Krešimir Rukavina presented a lecture dedicated to the application of CAR T-cell therapy as an innovative approach in the treatment of SLE and other autoimmune diseases. Current standard treatments – comprising immunosuppressants, glucocorticoids, antimalarials, and biologics – were discussed, with particular emphasis on challenges such as adverse effects, complications, immunogenicity, and poor patient adherence. Although rituximab has demonstrated efficacy, its limitations have spurred interest in alternative therapy such as CAR T-cells. The evolution of CAR T-cell therapy from oncology to autoimmune applications was reviewed, focusing on targeting B cells, which play a central role in SLE pathogenesis. Clinical experiences were shared, showcasing cases where patients achieved serologic remission or marked improvement with minimal adverse events. Nevertheless, several unresolved issues remain, including optimal patient selection, timing of therapy, long-term efficacy and safety, and the high cost of treatment. The most common adverse events reported were mild to moderate cytokine release syndrome (CRS) and rare occurrences of immune effector cell-associated neurotoxicity syndrome (ICANS). CAR T-cell therapy, as presented, holds significant promise for inducing sustained remission or potentially curing SLE and related autoimmune diseases.
In another presentation, Dr. Marija Šćepović-Ljucović shared the experience with anifrolumab therapy at the SLE Referral Center in Zagreb. Between July 2023 and September 2024, 17 patients were treated, predominantly women (88%), with an average age of 42 years and a mean disease duration of 9 years prior to therapy initiation. Data on demographic characteristics, clinical manifestations, laboratory parameters, and adverse events were systematically analyzed. The most common clinical manifestations included cutaneous and mucosal lesions, articular and hematological involvement, and constitutional symptoms, while renal involvement and antiphospholipid syndrome were less frequent. The majority of patients were concurrently treated with glucocorticoids, antimalarials, azathioprine, mycophenolate mofetil, and methotrexate. Out of 117 drug administrations, seven adverse events were reported, predominantly infectious complications such as pneumonia, bronchitis, and COVID-19. Therapy was discontinued in several cases due to inadequate efficacy or infectious complications. The most significant therapeutic benefits of anifrolumab were observed in the improvement of cutaneous, mucosal, and constitutional symptoms. Disease activity indices (SLEDAI 2K, SLE DAS, ECLAM, VAS) demonstrated a downward trend, indicating a favorable safety profile and supporting anifrolumab as a promising addition to the therapeutic arsenal for SLE.
Professor Miroslav Mayer concluded the symposium with a very interesting and insightful lecture on the use of ultrasound as a diagnostic tool in patients with SLE. Ultrasound has become an increasingly valuable tool in the assessment and management of SLE. In musculoskeletal involvement, ultrasound enables the detection of synovitis, tenosynovitis, and erosions, often revealing subclinical inflammation that may not be evident on physical examination. Compared to traditional radiography, ultrasound is more sensitive for early joint changes and allows for real-time dynamic assessment. In cardiac evaluation, echocardiography plays a critical role in identifying lupus-related cardiac manifestations, such as pericardial effusion, Libman-Sacks endocarditis, and myocardial involvement. Early detection of these complications significantly influences treatment decisions and long-term outcomes. Pleural involvement, often presenting as pleuritis or pleural effusion, is another common feature in SLE, and thoracic ultrasound provides a non-invasive, highly sensitive method to assess pleural pathology. It offers advantages over chest radiography, particularly in detecting small effusions and guiding thoracocentesis when needed. Ultrasound also aids in differentiating between active inflammatory processes and chronic fibrotic changes. Its portability, lack of ionizing radiation, and ability to be repeated as needed make ultrasound an ideal imaging modality in both outpatient and inpatient settings. Moreover, ultrasound can assist in monitoring treatment response and detecting early relapse in musculoskeletal and serosal disease. The growing use of point-of-care ultrasound (POCUS) further enhances its accessibility and utility in rheumatology practice. In conclusion, ultrasound represents an essential, versatile extension of the clinical examination in SLE, contributing to a more accurate and timely diagnosis, better disease monitoring, and improved patient care.
Following the insightful lectures, a discussion session was held, chaired by the panelists Professor Srđan Novak from Rijeka, Professor Jasminka Milas-Ahić from Osijek, and Professor Dijana Perković from Split. The Fourth Symposium marking World Lupus Day was met with great interest and participation, attracting rheumatologists as well as other medical specialists from all regions of Croatia. The symposium once again highlighted the importance of continuous education and collaboration among specialists in improving the care and outcomes for patients with SLE.
doc. dr. sc. Marija Bakula
Marija Bakula