Epidemiology and treatment patterns of Systemic Lupus Erythematous: real-world evidence from primary care databases in UK, Italy, Belgium, Germany, Spain, and Romania

Introduction Systemic Lupus Erythematosus (SLE) is a relapsing–remitting autoimmune disease with heterogeneous organ involvement and substantial long-term burden. Contemporary, population-based estimates for Europe remain variable, and real-world treatment uptake may lag behind guideline recommendations. This dissertation quantified adult SLE incidence and prevalence in multiple European countries, characterized incident cases against matched controls, and described post-diagnosis treatment patterns. Methods We conducted observational cohort analyzes using The Health Improvement Network (THIN®) general practice electronic health records (2017–2022). Adults (≥18 years) contributed person-time while active in participating practices. The main case definition required either a diagnostic code for SLE (excluding cutaneous-only lupus) or ≥2 adapted EULAR/ACR items plus laboratory or pharmacologic confirmation around the Index Date (ID). For epidemiology, we estimated the annual rates of crude and standardized incidence and prevalence by country, sex, and age. For characterization, incident cases were matched 4:1 with controls on sex, age and country, and baseline covariates were compared. For treatment, we followed incident cases with ≥24 months post-ID observation, classifying exposure in 6-month windows to Hydroxychloroquine (HCQ), glucocorticoids, NSAIDs, conventional immunomodulators/immunosuppressants, biologic agents, and cyclophosphamide/rituximab. The determinants of any treatment by 24 months were examined with logistic regression. Results By 2022, the standardized incidence was the highest in Spain (≈9–10 per 100,000 Person-Years (PY)) and Italy (8.20), intermediate in the UK (5.05) and Romania (4.16), and lowest in Belgium (1.30); Germany solely contributed prevalence estimates due to a limited look-back period. The standardized prevalence was highest in the UK (96.37 per 100,000), intermediate in Italy (58.91) and Spain (57.95), and lower in Germany (44.04), Belgium (29.87), and Romania (20.28). Incidence was largely stable within countries and prevalence rose steadily everywhere. Compared to matched controls, incident cases showed greater multi-morbidity and polypharmacy, with consistent excesses in cardiovascular disease, hypertension, mood/anxiety disorders, osteoporosis, malignancy and concomitant autoimmune diagnoses. During the semester immediately after diagnosis, in the pooled cohort near 40% of subjects were treated (≈60% in Italy); HCQ was most common at diagnosis (≈20–35% by country) and persisted for 24 months, while conventional immunosuppressants remained ≈10% and chronic glucocorticoids/NSAIDs ≈5–10%. Treatment flows were concentrated in the first 6 months, with high initiation and persistence of HCQ. Female sex and concomitant rheumatoid arthritis (and, in Spain, Sjogren’s syndrome) were associated with treatment received in the first 24 months after diagnosis, while baseline neuropsychiatric symptoms were inversely associated. Conclusions The burden of adult SLE in European primary care is substantial and is increasing in prevalence, with incidence and prevalence patterns across countries broadly consistent with previous literature but shaped by the maturity of the data-source and the evolving classification. Patients present with significant comorbidity at diagnosis. Routine care remains anchored in HCQ with comparatively restricted chronic steroid signals, but untreated patients and modest escalation in steroid-sparing agents persist. These findings underscore opportunities for earlier, guideline-concordant immunomodulation and pathway optimization, particularly for neuropsychiatric presentations, to reduce flares, damage accrual, and downstream healthcare burden.

Introduzione Il lupus eritematoso sistemico (LES) è una malattia autoimmune recidivante-remittente, a coinvolgimento d’organo eterogeneo e con rilevante impatto a lungo termine. Le stime population-based europee risultano variabili e l’adozione dei trattamenti nel real world può non allinearsi pienamente alle raccomandazioni. Questa tesi quantifica incidenza e prevalenza nell’adulto in più Paesi europei, caratterizza i casi incidenti rispetto a controlli appaiati e descrive i pattern terapeutici post-diagnosi. Metodi Studi di coorte osservazionali su cartelle cliniche elettroniche di medicina generale THIN® (2017–2022). Adulti (≥18 anni) contribuivano tempo a rischio quando attivi presso i medici partecipanti. La definizione principale di caso richiedeva un codice di LES (escludendo lupus cutaneo isolato) oppure ≥2 item EULAR/ACR adattati con conferma laboratoristica o farmacologica attorno alla data indice (DI). Per l’epidemiologia abbiamo stimato, per anno e Paese, tassi grezzi e standardizzati di incidenza e prevalenza per sesso/età. Per la caratterizzazione, i casi incidenti sono stati appaiati 4:1 a controlli per sesso, età e Paese. Per i trattamenti, abbiamo seguito i casi con ≥24 mesi post-DI, classificando in finestre semestrali l’esposizione a idrossiclorochina (HCQ), glucocorticoidi, FANS, immunomodulanti/immunosoppressori, biologici e ciclofosfamide/rituximab. I determinanti dell’aver ricevuto qualunque trattamento entro 24 mesi sono stati valutati con regressione logistica. Risultati Nel 2022 l’incidenza standardizzata era più alta in Spagna (≈9–10 per 100.000 anni-persona) e Italia (8,20), intermedia nel Regno Unito (5,05) e Romania (4,16), più bassa in Belgio (1,30); la Germania ha contribuito solo con prevalenza per limitato look-back. La prevalenza standardizzata risultava massima nel Regno Unito (96,37 per 100.000), intermedia in Italia (58,91) e Spagna (57,95), inferiore in Germania (44,04), Belgio (29,87) e Romania (20,28). L’incidenza è rimasta per lo più stabile, mentre la prevalenza è aumentata ovunque. Verso i controlli, i casi incidenti mostravano più multimorbidità e polifarmacoterapia, con eccessi di malattie cardiovascolari, ipertensione, disturbi dell’umore/ansia, osteoporosi, neoplasie e co-diagnosi autoimmuni. Nel semestre successivo alla diagnosi ≈40% era trattato nel pool (≈60% in Italia); HCQ era la terapia più comune (≈20–35% per Paese) e persisteva a 24 mesi; immunosoppressori ≈10%, glucocorticoidi/FANS cronici ≈5–10%. I flussi terapeutici si concentravano nei primi 6 mesi. Il trattamento entro 24 mesi era più probabile nel sesso femminile e con artrite reumatoide (in Spagna anche Sjögren), mentre la sintomatologia neuropsichiatrica basale mostrava associazione inversa. Conclusioni Il carico del LES nell’adulto in cure primarie europee è sostanziale e in crescita in prevalenza; i livelli e i profili per Paese sono in larga parte coerenti con la letteratura, ma risentono della maturità della fonte dati e dell’evoluzione classificativa. I pazienti presentano significativa comorbilità già alla diagnosi. La pratica routinaria resta centrata su HCQ con segnali contenuti di steroidi cronici; permangono quote di non trattati e un’escalation moderata verso agenti steroid-sparing. Anticipare e rafforzare un’immunomodulazione conforme alle linee guida, specie nei quadri neuropsichiatrici, potrebbe ridurre riacutizzazioni, danno cumulativo e onere sanitario.