Lupus

Tribolet de Abreu, Inês; Pereira-Amaral, Inês; Lopes, Leonor

doi: 10.1177/09612033261465930pmid: N/A

Cintron, Dahima; Pinotti, Caitlan; Rogers, Jennifer L; Sun, Kai; Sadun, Rebecca; Maheswaranathan, Mithu; Doss, Jayanth; Criscione-Schreiber, Lisa; Clowse, Megan E.B.

doi: 10.1177/09612033261458437pmid: 42236197

Background/PurposeMycophenolate compound (MMF, to represent both mycophenolate mofetil and mycophenolic acid) is an immunosuppressant used to treat Systemic Lupus Erythematosus (SLE). Due to its teratogenicity, the FDA recommends universal mycophenolate Risk Evaluation and Mitigations Strategies (MREMS) to prevent unplanned pregnancies and minimize fetal exposure. This quality improvement initiative aimed to improve documentation of the MREMS protocol in the encounter clinic note from 0% to 75% within 14 months.MethodsThe project was conducted in an academic lupus clinic from February 2023 to May 2024, with the intervention beginning in March 2023. MREMS was recommended for adult female SLE patients aged 18–50 on MMF, excluding those with hysterectomy. Interventions included provider and nurse education, nursing algorithms for identifying eligible patients and ordering pregnancy tests, electronic health record template updates, and regular feedback. Required documentation included counseling on MMF teratogenicity and contraception, with pregnancy testing at each visit. Control charts monitored documentation of MREMS counseling and pregnancy testing, and a one-year post-implementation follow-up was completed.ResultsAmong eligible encounters (n = 89), MREMS documentation increased from 0% to an average of 24% during the first 8 months of PDSA cycles, then shifted to an average of 67% of encounters. We reached and sustained our documentation goal of 75% for the last three consecutive months. Pregnancy-test ordering rose from 0% to 63%, and contraception was documented at 98% of visits. Over the course of the intervention, no pregnancies were exposed to MMF. MREMS documentation and pregnancy screening remained above 75% of encounters 1 year after intervention.ConclusionUsing quality improvement cycles, we incorporated a two-part MREMS protocol into a busy academic lupus clinic, with improved documentation and pregnancy screening.

Hara, Natsuko; Okamoto, Yuko; Katsumata, Yasuhiro

doi: 10.1177/09612033261465928pmid: N/A

ObjectiveThis study aimed to investigate belimumab continuation and identify clinical parameters predicting belimumab continuation in patients with systemic lupus erythematosus (SLE) in a real-world setting.MethodsA total of 38 consecutive patients with SLE who were newly treated with belimumab at our institution from 2018 to 2024 were retrospectively analyzed. The data were censored when belimumab was discontinued or the observation period ended. Clinical and laboratory data were retrospectively collected.ResultsThe median follow-up time after starting belimumab was 37 months (IQR 12–52). The 1-year belimumab continuation rate was 29/38 (76%). During the entire observation period, 15 (39%) patients discontinued belimumab. Among the 10 patients who discontinued belimumab due to lack of efficacy, seven were switched to other biologics. The overall discontinuation rate was 13.4 per 100 person-years. Absence of serological activity (increased anti-dsDNA and/or hypocomplementemia) at baseline was a significant risk factor for belimumab discontinuation within 1 year (p = 0.034), with a relative risk of 3.43 (95% CI, 1.01–11.6). The glucocorticoid dosage was significantly reduced in the 29 patients treated with belimumab for ≥12 months (p < 0.001). Among the 33 patients who were not in the low disease activity state (LLDAS) at baseline, 19 (58%) were in the LLDAS at their final visit (p < 0.001). Belimumab was temporarily discontinued in six patients due to infection, but all patients resumed it.ConclusionThe belimumab continuation rate was high among patients with SLE in real-world settings; however, the absence of serological activity at belimumab initiation was a significant risk factor for discontinuation within 1 year.

Castellana, Eleonora; Chiappetta, Maria Rachele

doi: 10.1177/09612033261458427pmid: 42224076

BackgroundAnifrolumab and belimumab are the two biologic agents currently approved for moderate-to-severe systemic lupus erythematosus (SLE), targeting distinct immunological pathways. While their efficacy has been established in randomized controlled trials, their comparative safety profiles in real-world settings remain incompletely characterized.MethodsA retrospective pharmacovigilance study was conducted using data from the FDA Adverse Event Monitoring System (AEMS) from January 1, 2011 to March 30, 2026. Individual Case Safety Reports (ICSRs) were extracted using “anifrolumab,” “anifrolumab-Fnia,” and “belimumab” as search terms. Adverse drug reactions (ADRs) were coded according to MedDRA version 28.1 Preferred Terms. A disproportionality analysis was performed using the Reporting Odds Ratio (ROR) with 95% confidence intervals; a p-value <0.05 was considered statistically significant.ResultsA total of 2124 ICSRs for anifrolumab and 30,107 for belimumab were identified. Female patients predominated in both groups, consistent with SLE epidemiology. Herpes zoster showed a strong and statistically significant association with anifrolumab (ROR = 5.13; 95% CI: 3.97–6.62; p < 0.0001), consistent with its type I interferon receptor antagonism mechanism. Belimumab was more frequently associated with administration-related events, including missed doses, device misuse, and injection site pain. No statistically significant differences were observed for fatigue, arthralgia, headache, nausea, or rash.ConclusionsAnifrolumab and belimumab exhibit distinct safety profiles. Anifrolumab carries a significantly higher risk of herpes zoster infection, warranting pre-treatment vaccination assessment. Belimumab shows a predominance of administration-related and non-serious events. Treatment selection should be individualized based on patient-specific risk factors, infection susceptibility, and adherence considerations.

Strizzi, Camillo Tancredi; Cheungpasitporn, Wisit; Thongprayoon, Charat; Pesce, Francesco

doi: 10.1177/09612033261454511pmid: 42161343

BackgroundThe clinical heterogeneity of systemic lupus erythematosus exceeds the resolution of conventional disease activity instruments. Artificial intelligence offers the analytical infrastructure to engage with this complexity, yet the translation of AI models into clinical practice remains limited.MethodsThis review critically appraises the current evidence for AI applications across the SLE clinical workflow, including computational phenotyping, diagnosis, disease activity monitoring, organ-specific predictive modelling, and treatment personalization. Studies were evaluated for external validation, prospective testing, algorithmic fairness, explainability, and regulatory status.FindingsAI applications across the SLE clinical workflow show uneven methodological maturity. Diagnostic and monitoring tools include the SLERPI index, with multinational external validation, and an LSTM flare-prediction model (C-index 0.897). Treatment personalization is anchored by serum IgA2 anti-dsDNA, the only SLE response biomarker validated across independent trials, and by multi-stain deep learning on renal biopsies (AUC 0.84, three external centers). Predictive modelling for organ-specific manifestations has progressed unevenly: cardiovascular risk stratification (SLECRISK) and a multicenter thrombocytopenia model are the most mature, while neuropsychiatric, gastrointestinal, and ocular applications remain single-center proofs of concept. External validation is the exception across SLE prediction models, no AI tool has received regulatory clearance, and populations most affected by SLE remain underrepresented in training data.ConclusionsAI demonstrates genuine analytical capability in SLE but the translation gap is defined by insufficient validation, limited explainability, and absent equity evidence. Closing it will require fewer published models and more validated tools, optimization for clinical impact rather than discrimination alone, and demonstration of performance equity across the demographic spectrum of the disease.

Rodelo-Ceballos, Joaquín; Restrepo-Escobar, Mauricio; Ustariz, Jose; Taborda, Alejandra; González, Luis Alonso

doi: 10.1177/09612033261458574pmid: 42249630

BackgroundPure membranous lupus nephritis (MLN) generally has a better kidney prognosis than proliferative lupus nephritis (PLN), but comparative data from Latin America remain limited. We evaluated clinical features and kidney outcomes of MLN in a Colombian cohort and compared them with proliferative forms.MethodsWe retrospectively included adults (≥18 years) with first biopsy-proven MLN or PLN at a Colombian tertiary center. Clinical and histopathological features were compared between pure MLN (Class V) and PLN (Class III/IV ± V). Factors associated with MLN were analyzed using logistic regression. Kidney survival was estimated using Kaplan-Meier analysis, and predictors of end-stage kidney disease (ESKD) were assessed using Cox proportional hazards regression analyses. Because death could preclude observation of ESKD, competing-risks analyses were performed using cumulative incidence functions and Fine–Gray subdistribution hazard models with death treated as a competing event.ResultsOf 371 patients, 54 (14.6%) had MLN and 317 (85.4%) had PLN. Compared with PLN, patients with MLN have lower immunological activity, better kidney function, less active urinary sediment at biopsy, and lower modified NIH activity and chronicity indices scores. In multivariable logistic regression, higher eGFR was independently associated with MLN (OR 1.02, 95% CI 1.01−1.03), whereas anti-dsDNA positivity was inversely associated (OR 0.33, 95% CI 0.15−0.71). In univariable Cox analysis, MLN was associated with lower ESKD risk (HR 0.12, 95% CI 0.03−0.48); but this association was not confirmed in multivariable analysis, which was underpowered because only 2 ESKD events occurred in the MLN group. In competing-risks analysis, MLN was associated with a lower unadjusted subdistribution hazard of ESKD (SHR 0.13, 95% CI 0.03−0.51), but not after adjustment for baseline eGFR and modified NIH indices (adjusted SHR 0.46, 95% CI 0.11−2.00). Kaplan–Meier analysis showed higher crude renal survival in MLN than in PLN.ConclusionIn this Latin American cohort, MLN exhibited a distinct baseline profile characterized by lower inflammatory activity and better-preserved kidney function at presentation. Although crude and competing-risk analyses suggested a more favorable renal trajectory for MLN, the study was underpowered to confirm an independent effect of MLN on ESKD after adjustment.

Ponce, A.; Rodríguez-Pintó, I.; Pons, I.; Jerez, A.; Toledano, P.; Rossiñol, T.; Vilaplana, B.; Espinosa, G.; Cervera, R.

doi: 10.1177/09612033261461987pmid: 42294990

ObjectiveTo describe the prevalence, clinical manifestations, histopathological features, and antibody profile associated to skin involvement in patients with catastrophic antiphospholipid syndrome (CAPS).MethodsWe performed a cross-sectional study of the patients included in the “CAPS Registry,” a registry developed by the European Forum on Antiphospholipid Antibodies (aPL)1,2 This database contains data from patients with CAPS collected from April 1992 to December 2024. Demographic clinical manifestations, laboratory features (including aPL antibodies), pathological findings in involved skin, and outcome were retrieved.ResultsCutaneous involvement was described in 377 episodes (47%) from 361 patients. A female sex prevalence of 49.4% was observed. The average age was 39.4 (SD ± 17.9) years. The more frequent skin manifestations observed were livedo reticularis (17.6%), skin necrosis (13%), ischemic ulcers (10.4%), skin ischemic (9.7%), skin purpura (7.1%), gangrene (5%), splinter haemorrhages (2.6%), and Raynaud’s phenomenon (1.5%). The most frequently affected organs in CAPS episodes with skin involvement were kidneys (72%), lungs (61%), central nervous system (54.5%), and heart (54.4%). Thrombocytopenia and hemolysis features were more common in patients with skin involvement (p < 0.05 for all). Thrombotic microangiopathy was the predominant pathological finding, present in 82 (68.3%) episodes. No difference regarding mortality were found in episodes with or without skin involvement (29.3% vs 32.1%, p = 0.42).ConclusionThe presence of skin involvement in patients with CAPS is frequent. The most frequent manifestations were livedo reticularis and skin necrosis. Skin involvement does not seem to be associated to mortality.

Soleimani, Fatemeh; Karbalaei-Musa, Hamidreza; Hajali, Mohammad Hossein; Kenarangi, Taiebe; Mosallaei, Meysam; Ansari, Narges

doi: 10.1177/09612033261458560pmid: 42233280

ObjectiveSystemic lupus erythematosus (SLE) is a multifactorial autoimmune disease in which dysregulated nucleic acid sensing and type I interferon responses drive autoantibody production and organ damage. Toll-like receptor 9 (TLR9) regulates these pathways, and promoter variants (rs187084 and rs5743836) may alter TLR9 expression and modulate disease susceptibility and severity. This study evaluated the association of these promoter SNPs and their haplotypes with SLE risk and clinical/laboratory features in an Iranian population.MethodsIn this case–control study, we genotyped TLR9 promoter SNPs rs187084 and rs5743836 in 140 SLE patients and 140 age- and sex-matched healthy controls using the real-time PCR-high resolution melting (PCR-HRM) assay.ResultsOur analysis showed that the CC and CT genotypes and the C allele of the rs5743836 SNP were associated with an increased risk of SLE (P < 0.05). However, there was no association between the rs187084 SNP and the risk of SLE (P > 0.05). The combined rs187084–rs5743836 CC haplotype was associated with increased SLE risk (CC vs TT haplotype, P < 0.001). Furthermore, in the patient group, carriers of the C allele in both promoter variants exhibited earlier disease onset and more active and severe disease, as evidenced by higher levels of C-reactive protein (CRP) and anti-dsDNA, reduced complement C3 and C4, and a higher frequency of renal and neurological complications (P < 0.05).ConclusionOur data suggest that promoter variation in TLR9, specifically the rs5743836 C allele and the combined rs187084-rs5743836 CC haplotype, is linked to an increased risk of SLE and more disease activity and severe clinical presentation.

Shaik, Nagoor; Nweke, Ugochukwu C; Jolly, Meenakshi

doi: 10.1177/09612033261458430pmid: 42258616

ObjectiveWe evaluated the reading & comprehension levels of Systemic Lupus Erythematosus (SLE) Patient educational materials (PEMs) available online, from both nonprofit and for-profit organizations.MethodsWe analyzed PEMs from four nonprofit organizations (American College of Rheumatology [ACR], Lupus Foundation of America [LFA], Lupus Research Alliance [LRA], Lupus Society of Illinois [LSI]) & three for-profit company’s platforms (Aurinia, AstraZeneca, GlaxoSmithKline [GSK]). Reading & comprehension scores were calculated using six standard tools, and comparisons were performed using one-way ANOVA & Tukey’s post-hoc analysis. A p-value ≤0.05 was considered statistically significant.ResultsThe average Flesch–Kincaid Grade Level (FKGL) and Flesch Reading Ease Score (FRES) across all PEMs were 10.05 ± 0.70 and 52.68 ± 4.10, respectively. Materials from nonprofit organizations had a FKGL of 10.35 ± 0.88 and a FRES of 51.19 ± 4.91, indicating a reading level requiring 10th- to 12th-grade proficiency. For-profit organizations had a slightly lower FKGL of 9.98 ± 0.42 and a higher FRES of 54.35 ± 2.65. These differences were not statistically significant (p = 0.53 and 0.16). However, significant within-group differences were observed. Among nonprofits, PEMs from LFA had the most favorable readability metrics (FKGL 9.19 ± 0.44, FRES 58.34 ± 3.11), compared to ACR (10.64 ± 0.56, 49.81 ± 2.24), LRA (10.53 ± 0.61, 50.54 ± 2.69), and LSI (11.28 ± 0.45, 45.64 ± 2.03) (p < 0.01). Among for-profits, PEMs from Aurinia had significantly better readability scores (FKGL 9.59 ± 0.46, FRES 55.77 ± 3.05) than those from AstraZeneca (9.93 ± 0.38, 53.13 ± 2.48) and GSK (9.86 ± 0.25, 54.28 ± 2.16) (p < 0.001).ConclusionMost SLE patient education materials available online are written at or above a 10th-grade level. These findings highlight the urgent need to improve PEM readability to support patients with lower health literacy.

Etchegaray-Morales, Ivet; Mendoza-Pinto, Claudia; Munguía-Realpozo, Pamela; Molina-Vélez, Diana; Hernández-Ávila, Juan Eugenio; Ramírez-Lara, Edith; Torres-Jiménez, Alfonso Ragnar; Osorio-Peña, Ángel David; Méndez-Martínez, Socorro

doi: 10.1177/09612033261445759