Miriam Retuerto-Guerrero

Background: Obesity and type 2 diabetes are common in rheumatology, often exacerbated by glucocorticoids. Real-world data on glucagon-like peptide-1 receptor agonists (GLP-1RAs) in this setting remain limited. Objectives: To evaluate the metabolic effectiveness and safety of GLP-1RAs in rheumatology outpatients, including inflammatory marker and subgroup analyses. Methods: Single-centre retrospective study (October 2024–October 2025) including 119 patients (from 169 screened) treated with GLP-1RAs. Paired analyses were performed at 3, 6 and 12 months. Exploratory comparisons included participants with chronic inflammatory arthritis (n=46) and those with non-inflammatory disease (n=43). Results: Patients had high baseline cardiometabolic burden (mean body mass index (BMI) 34.9±9.9 kg/m²; diabetes 96.6%). GLP-1RA initiation was associated with sustained weight loss: −4.0 kg, −4.5 kg and −7.7 kg at 3, 6 and 12 months (all p<0.001; −8.2% at 12 months), with 56.5% improving ≥1 BMI category. Haemoglobin A1c decreased by −0.97%, −0.69% and −0.91% (all p<0.001), alongside significant reductions in fasting glucose (up to −24.8 mg/dL; p<0.001). Lipid improvements included reductions in low-density lipoprotein-cholesterol (−12.2 mg/dL; p=0.006) and triglycerides (−21.7 mg/dL; p=0.007). At 12 months, erythrocyte sedimentation rate decreased significantly (p=0.023), while CRP showed a non-significant decline (p=0.076); both were significantly reduced in the inflammatory subgroup. No significant differences were observed between inflammatory and non-inflammatory groups in adjusted metabolic trajectories. Adverse events were mainly gastrointestinal (13.4%); pancreatitis (0.8%) and cholecystitis (1.7%) were rare. Discontinuation occurred in 6.7%. One death (mesenteric ischaemia) had unclear causality. Conclusions: GLP-1RAs were associated with meaningful metabolic improvements in patients with rheumatic diseases, with a favourable safety profile. Potential anti-inflammatory effects require confirmation in prospective studies.

Immunosuppressive therapies increase the risk of infection, but there is little information regarding their effects on cellular antimycobacterial activity. In this context, the aim was to evaluate in vitro the impact of commonly used immunosuppressive drugs on the ability of peripheral blood mononuclear cells (PBMCs), neutrophils (polymorphonuclear cells, PMNs), and monocyte-derived macrophages (MDMs) to control Mycobacterium abscessus. Biofilm formation was assessed by quantifying bacterial colonies in cellular cultures (BCCCs) and bacterial viability by colony-forming units (CFUs). BCCCs showed significant differences among treatment conditions in PBMCs. The median (interquartile range) BCCC values for tacrolimus (TAC) 16.5 (41), everolimus (EVE) 11 (33), methotrexate (MTX) 12.5 (22) and leflunomide (LEF) 11 (29) were all significantly higher than the negative control (DMSO) 5 (14), indicating that these immunosuppressants impaired the ability of PBMCs to restrict BCCC formation. Log-transformed CFUs also varied across treatments in PMNs. Mycophenolic acid (MPA) 5.98 (2.61) and EVE 5.85 (2.77) increased LogCFU recovery compared with DMSO 5.58 (2.63), whereas MTX 5.18 (2.74) decreased it. In contrast, immunosuppressants had no significant overall effect in MDM cultures. Interestingly, 6-mercaptopurine (6MP) affected the size of colonies. Prednisolone, as expected, but also MTX and LEF, inhibited the expression in infected PBMCs of IL-1β, IL-1Ra, IL-6, CCL3, CCL5, CXCL8 and TIMP-2, whereas IL-10, CCL2 and CXCL7 expression remained essentially unchanged. Unexpectedly, methotrexate promoted CXCL8 expression, a chemokine for PMNs. These results show that commonly used immunosuppressive drugs can differentially modulate the antimycobacterial activity of PBMCs and innate immune cells, affecting both mycobacterial viability and biofilm formation.

Mycobacteria isolated only once in repeated sputum cultures are deemed colonizers that are not normally present in the lungs despite their ubiquitous presence in the environment. We have developed a sensitive and specific PCR assay to detect slow-growing mycobacteria in culture negative sputum and have found them in 30% of the samples obtained from individuals with clinical suspicion of tuberculosis or mycobacteriosis (n = 50) and in 45% of the samples from individuals with no suspicion (n = 49). As a negative control we have analyzed infections from an extra-pulmonary location, the urinary tract (n = 21), in which mycobacterioses are rare, and did not detect them. The load of bacteria in the lungs is kept low by the defense mechanisms of the host, and mycobacteria are not normally detected in sputum cultures. Their incidental isolation would not be a consequence of a new exposure to the microorganism but a sign of susceptibility to mycobacteriosis.

Background: Anifrolumab is approved for adults with moderate-to-severe active systemic lupus erythematosus (SLE) based on Randomised clinical trials (RCTs). While randomised pivotal RCTs have demonstrated their efficacy and safety, real-world evidence (RWE) remains limited. Objectives: To describe the clinical characteristics, effectiveness and safety of anifrolumab in clinical practice and to assess findings from published observational studies. Methods: Multicentre study of patients with SLE classified according to EULAR/American College of Rheumatology (ACR) 2019. Data were collected from medical records up to 30 April 2025. Variables included demographic characteristics, clinical and serological features, prior and concomitant therapies, disease activity indices including the SLE Disease Activity Index 2000 (SLEDAI-2K), SLE Disease Activity Score (SLE-DAS) and Physician Global Assessment (PGA), damage and disease control measures including the Systemic Lupus International Collaborating Clinics/ACR Damage Index, Lupus Low Disease Activity State (LLDAS) and Definitions of Remission in SLE (DORIS) remission and the association with adverse events (AEs). A review of published observational studies was also conducted. Results: We included 206 patients (183 women; mean age 44.6±12.6 years) from 54 Spanish centres. The most common indications for anifrolumab were cutaneous (61.7%), musculoskeletal (48.5%) and haematological (27.2%). A rapid and sustained improvement was observed in disease activity (SLEDAI-2K, SLE-DAS, PGA), LLDAS, DORIS remission, serological markers (anti-double-stranded DNA, C3/C4) and corticosteroid tapering. Organ damage remained stable. After a mean follow-up of 7.5±5.3 months, the most frequent AEs were herpes zoster (n= 5), respiratory infections (n= 6) and headache (n= 3). Twenty patients discontinued treatment. These results were consistent with published observational studies. Conclusion: In this large RWE cohort, anifrolumab demonstrated early and sustained clinical benefit, a favourable safety profile and a significant corticosteroid-sparing effect. These findings reinforce the evidence from CT and support the incorporation of anifrolumab into routine care for patients with SLE.

Background and Clinical Significance: Isolated mediastinal lymphadenopathy is an exceptionally rare and diagnostically challenging initial manifestation of microscopic polyangiitis (MPA), often mimicking malignancy or infection. This case highlights the pivotal role of an innovative minimally invasive technique in achieving a definitive diagnosis. To the best of our knowledge, this is the first reported case of MPA diagnosed via EBUS-TMC. Case Presentation: A 55-year-old male livestock farmer from a rural area with a history of recurrent pneumonia presented with four weeks of persistent fever, significant weight loss (7 kg), myalgia, and asthenia. Physical examination revealed fever and cachexia. Notable findings included leukocytosis (17,000/μL), normocytic anemia, thrombocytosis (672,000/μL), highly elevated inflammatory markers (CRP 145 mg/L, ESR 120 mm/h), and strongly positive MPO-ANCA (>134 U/mL). Serological testing was significant for IgG antibodies against Coxiella burnetii (Phase I 1:64, Phase II 1:256). PET-CT imaging demonstrated hypermetabolic bilateral hilar and mediastinal lymphadenopathy. Diagnostic challenges included overlapping serological findings suggestive of past Coxiella burnetii exposure. Endobronchial ultrasound–guided transbronchial mediastinal cryobiopsy (EBUS-TMC) of a subcarinal lymph node was performed, providing a high-quality sample that revealed neutrophilic small-vessel vasculitis with fibrinoid necrosis, definitive for MPA. Immunosuppressive therapy with high-dose corticosteroids and rituximab (1000 mg on days 1 and 15) was initiated, leading to the complete resolution of all constitutional symptoms. Conclusions: This case illustrates that EBUS-TMC is a safe and highly effective diagnostic tool for obtaining critical histological evidence in systemic vasculitides with atypical presentations. This technique should be considered in the diagnostic algorithm for unexplained mediastinal lymphadenopathy to avoid more invasive surgical procedures.

Objective: To assess real-world outcomes of anifrolumab (ANI) in refractory systemic DM. Methods: This multicentre and multidisciplinary, retrospective study evaluated 30 DM patients receiving ANI through compassionate use. Disease activity was assessed at baseline and months 1, 3, 6 and 12 using Cutaneous Dermatomyositis Disease Area and Severity Index Activity Score (CDASI-A), Manual Muscle Testing-8 (MMT-8), joint and pulmonary evaluation and glucocorticoid tapering. Safety included adverse event documentation and treatment discontinuation rates. Results: Treatment indications included refractory cutaneous (73.3%), cutaneous-muscular (13.4%, including one pulmonary progression case) and other manifestations (13.3%). ANI was initiated without concomitant immunosuppressive therapy in 50% of patients. Cutaneous improvement was observed from month 1 (CDASI-A: 23 [IQR 10.8–30.5] to 6 [IQR 3–10]; P < 0.001), with heliotrope rash and Gottron’s papules responding faster than alopecia. Muscular function improved (MMT-8: 142.5 [IQR 127–148] to 146.5 [IQR 139–150]; P < 0.05) with creatine kinase (CK) normalization (332 IU/l [IQR 211.5–893.5] to 146 IU/l [IQR 106.5–481.8]) at month 1. All active arthritis patients (n = 3) achieved remission, with no articular flares observed among patients with historical joint involvement. Interstitial lung disease cases (n = 6) demonstrated stabilization or improvement as assessed by pulmonary function tests and/or computed tomography. Glucocorticoid dose significantly reduced (P < 0.001), discontinued in 50%. Adverse events were mild (16.7% patients); one 89-year-old patient died from pneumonia. One patient required upadacitinib for refractory pruritus; one discontinued ANI for efficacy loss. Conclusion: ANI showed rapid, multisystem efficacy in refractory DM with significant steroid-sparing effects and a favourable safety profile.

J Rheumatol 2025; doi: 10.3899/jrheum.2025-0658 In the 4th paragraph regarding severe hematological involvement, the criterion for severe leukopenia should be a leukocyte count of < 2 × 10⁹/L. The revised text is "severe leukopenia (leukocyte count < 2 × 10⁹/L)." This correction applies only to the October 1 First Release. The correct text appears in the print and online issues.

Objective: To evaluate the real-world safety and efficacy of macitentan (MACI) in patients with systemic autoimmune rheumatic diseases (SARDs) and refractory digital ulcers (DUs). Methods: We conducted a retrospective observational study of 42 patients treated with MACI (10 mg/day) on a compassionate-use basis across Spanish reference hospitals. Given the cohort’s heterogeneity, a two-step analysis was performed: a global assessment of all patients, followed by a subgroup analysis restricted to those with systemic sclerosis (SSc) or fulfilling very early SSc (VEDOSS) criteria to explore predictors of response. Efficacy was defined as complete healing, partial response, or a lack of response based on physician assessment. Safety was evaluated through analysis of adverse events. Results: In the global cohort, MACI demonstrated a high rate of complete ulcer healing (82.9%) at the 3-month follow-up, with a significant reduction in median ulcer count (p < 0.001). Subgroup analysis within the SSc/VEDOSS cohort (n = 36) revealed that the presence of gastrointestinal involvement (GI) and a higher baseline DUs were significant predictors of a poorer therapeutic response (p = 0.022 and p = 0.028). The drug was well-tolerated; adverse events were infrequent and rarely led to treatment discontinuation. Conclusions: In this real-world refractory population, MACI was associated with rapid DU healing and a favorable safety profile. GI and higher ulcer burden predicted diminished treatment response in SSc patients. These results support the use of MACI as a valuable therapeutic option for severe digital vasculopathy in SARDs, although further prospective studies are warranted to confirm these observations.

Anifrolumab (ANI) is a monoclonal antibody targeting the interferon alpha receptor 1 (IFNAR1), used in patients with systemic lupus erythematosus (SLE). It has demonstrated particular efficacy in the cutaneous and musculoskeletal domains of SLE,^1,2 leading to its inclusion in the 2023 European Alliance of Associations for Rheumatology (EULAR) SLE treatment recommendations as an effective drug to control SLE flares and taper prednisone dose.³

Nontuberculous mycobacteria (NTM) are environmental and ubiquitous, but only a few species are associated with disease, often presented as nodular/bronchiectatic or cavitary pulmonary forms. Bronchiectasis, airways dilatations characterized by chronic productive cough, is the main presentation of NTM pulmonary disease. The current Cole’s vicious circle model for bronchiectasis proposes that it progresses from a damaging insult, such as pneumonia, that affects the respiratory epithelium and compromises mucociliary clearance mechanisms, allowing microorganisms to colonize the airways. An important bronchiectasis risk factor is primary ciliary dyskinesia, but other ciliopathies, such as those associated with connective tissue diseases, also seem to facilitate bronchiectasis, as may occur in Lady Windermere syndrome, caused by M. avium infection. Inhaled NTM may become part of the lung microbiome. If the dose is too large, they may grow excessively as a biofilm and lead to disease. The incidence of NTM pulmonary disease has increased in the last two decades, which may have influenced the parallel increase in bronchiectasis incidence. We propose that ciliary dyskinesia is the main promoter of bronchiectasis, and that the bacteria most frequently involved are NTM. Restoration of ciliary function and impairment of mycobacterial biofilm formation may provide effective therapeutic alternatives to antibiotics.