Beatriz Frade-Sosa

A substantial proportion of individuals with palindromic rheumatism develop rheumatoid arthritis (RA). This randomized, open-label, multicenter trial aimed to assess whether 2 years of treatment with abatacept ( n = 34; 125 mg subcutaneous injections weekly during the first year and every 2 weeks during the second year) compared with oral hydroxychloroquine ( n = 36; 5 mg kg ^{− 1} per day) could reduce the frequency of RA development in individuals with palindromic rheumatism positive for rheumatoid factor and/or anticitrullinated protein antibody. The primary outcome was the development of persistent arthritis that fulfilled the 2010 RA classification criteria of the American College of Rheumatology and the European Alliance of Associations for Rheumatology, as evaluated by the participant clinicians during the 24 months of follow-up. Secondary outcomes included the frequency, intensity and duration of joint attacks, the proportion of patients in remission and the frequency of adverse events. In the primary analysis, in the modified full analysis set with failure imputation, 7 (20.6%) of the 34 participants treated with abatacept and 18 (50.0%) of the 36 participants treated with hydroxychloroquine developed RA during the 24 months of follow-up ( P = 0.010; risk difference 29.4%, 95% confidence interval 8.2 to 50.7), meeting the primary endpoint. Using the available-data-only approach, the corresponding figures were 3 (10.0%) of 30 individuals and 10 (35.7%) of 28 individuals, respectively ( P = 0.019). Compared with participants treated with hydroxychloroquine, participants treated with abatacept had a significantly longer time to progression to RA (hazard ratio 0.27, 95% confidence interval 0.07 to 0.96; log-rank test P = 0.0299). Abatacept was also associated with a reduced intensity of joint attacks and a higher frequency of symptom remission; however, there were no differences in the frequency of attacks between the two study drugs. No relevant differences in the evolution of antimodified peptide and/or protein antibody titers were observed between the two treatment arms. Both drugs were well tolerated. In patients with seropositive palindromic rheumatism, compared with hydroxychloroquine, abatacept given for 2 years reduced the risk of progression to RA and improved symptoms. ClinicalTrials.gov identifier NCT03669367 and EudraCT no. 2017-004543-20.

Objectives: Belimumab (BEL) is an approved biologic therapy for systemic lupus erythematosus (SLE) that, when added to standard care, reduces disease activity, flare rates and glucocorticoid exposure. In clinical practice, BEL is frequently combined with conventional immunosuppressants (IS), but the added benefit of concomitant IS once disease control is achieved remains uncertain. Observational data suggest that BEL monotherapy may be effective in selected patients, but comparative real-world evidence is limited. Objectives were to evaluate the clinical effectiveness of BEL as monotherapy vs in combination with IS in patients with SLE included in the BEL-Spain Registry. Methods: We performed a retrospective analysis of SLE patients treated with BEL with or without IS, with at least 12 months of follow-up. The primary outcome was remission according to the 2021 DORIS definition. Secondary outcomes included Lupus Low Disease Activity State (LLDAS), flare rates and glucocorticoid use. Overlap propensity score weighting was applied to adjust for confounding by indication. Results: Among 258 patients, 177 (68.6%) received BEL with IS and 81 (31.4%) BEL monotherapy. At 12 months, DORIS remission rates were 48.1% in the IS group and 51.4% in the monotherapy group (P=NS), with comparable LLDAS and flare rates. Propensity score-adjusted analyses confirmed no significant differences in remission rates (OR 0.89, 95% CI 0.37–2.14). Global treatment trajectories were stable, other than progressive glucocorticoid reduction in both groups. Conclusion: In this real-world cohort, BEL monotherapy achieved similar outcomes to combination therapy with IS in selected SLE patients. Prospective studies are needed to confirm these findings and define optimal treatment strategies.

Background: Achieving low disease activity or remission in psoriatic arthritis (PsA) remains difficult. The GRAPPA group recently defined difficult-to-treat (D2T) PsA but did not include a time-based criterion. Objectives: This study aimed to evaluate the prevalence and features of D2T PsA using several operational definitions. Methods: A cross-sectional study at a tertiary center enrolled PsA patients with active disease confirmed by clinical exam and ultrasound. D2T PsA was defined by: (1) failure of ≥1 csDMARD plus ≥2 b/tsDMARDs with different mechanisms of action (GRAPPA definition); (2) ≥2 b/tsDMARDs with different mechanisms of action within 12 months (time-based definition); or (3) failure of >3 b/tsDMARDs with different mechanisms of action (very refractory). Clinical, demographic, radiographic, and ultrasound data were analyzed, and multivariable analyses identified independent associations. Results: Seventy-two patients (54.2% female, median age 56, disease duration 84 months) all had active disease (median DAPSA 17); 68% had comorbidities. Enthesitis, dactylitis, and nail disease were seen in 20.8%, 45.8%, and 41.7%. HLA-B27 positivity was 13.9%. Radiographic erosions and ultrasound paratenonitis were present in 37.5% and 33.3%. GRAPPA D2T criteria were met by 23.6%, linked to longer disease duration, higher activity, HLA-B27, comorbidities, and combined therapy. Time-based D2T (12.5%) showed higher DAPSA and nail involvement, with ultrasound paratenonitis and combined therapy independently associated. Very refractory patients (11.1%) only correlated with combined therapy. Conclusions: Up to one-fourth of PsA patients remain active despite multiple treatments. D2T PsA is associated with disease duration, comorbidities, activity, HLA-B27, combined therapies. Remarkably, patients who fulfilled the <12-month D2T definition were more likely to present with nail involvement and ultrasound-detected paratenonitis.

Objectives: To describe the clinical spectrum of VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic) syndrome in patients managed by rheumatology units and analyse genotype–phenotype correlations. Methods: A multicentre, cross-sectional, retrospective study was conducted across 126 Spanish hospitals. Patients with VEXAS syndrome diagnosed between December 2020 and January 2024 were included. Demographic data, clinical manifestations, laboratory findings, genetic analyses, treatments and outcomes were collected from medical records. Results: Thirty-nine male patients were included (mean age at diagnosis: 72.78 years). Common manifestations were cutaneous lesions (87.18%), polyarthritis (82.05%) and fever (79.49%). Renal involvement was observed in 20.51% of patients. Genetic testing confirmed ubiquitin-like modifier-activating enzyme 1 mutations in all cases: 18 M41L, 14 M41T, 6 M41V and 1 novel mutation of unknown significance at site c.209T>A. The M41V mutation was significantly associated with renal involvement, while M41T was linked to deep vein thrombosis and thrombocytopaenia. Glucocorticoids were used in all patients, with improved response rates post-diagnosis (55.26% vs 97.14%) probably influenced by an increase in administered doses. IL-6 inhibitors and JAK inhibitors showed promising response rates (75% and 76.92%, respectively). Conclusions: This study provides insights into the clinical spectrum of VEXAS syndrome in rheumatology settings, highlighting a higher prevalence of joint symptoms and renal involvement than previously reported. Genotype–phenotype correlations were observed, with M41V significantly associated with renal involvement and M41T linked to deep vein thrombosis and thrombocytopaenia. A new, presumably causative variant of VEXAS syndrome at site c.209T>A was described. These findings contribute to the growing understanding of VEXAS syndrome and may inform future diagnostic and treatment strategies.

A Clinical Case of Possible Pre-Rheumatoid Arthritis

Psoriatic arthritis (PsA) is a chronic inflammatory condition affecting about one-third of individuals with psoriasis. Defining axial involvement in PsA (axPsA) remains debated. While rheumatologists guide clinical practice, consensus on axPsA is still lacking. This paper explores historical and upcoming definitions from the Axial Involvement in Psoriatic Arthritis (AXIS) study, which aims to establish a validated axPsA definition. Epidemiological data reveal diverse axPsA prevalence rates, emphasizing its complex relationship with peripheral arthritis and enthesitis. Unique genetic, clinical, and radiological features differentiate axPsA from ankylosing spondylitis (AS), necessitating refined classification criteria. The recommendations from the Assessment of Spondylarthritis international Society (ASAS) provide valuable guidance due to the limited direct evidence. Emerging therapies, including interleukin-23 (IL-23) inhibitors or Janus kinase (JAK) inhibitors, are under investigation for axPsA. Currently, secukinumab, an interleukin-17 (IL-17) inhibitor, is an evidence-based option for axPsA management. However, given the variability in individual patient responses and disease manifestations, personalized, evidence-based treatment approaches remain essential for optimizing patient outcomes. In the final section, two real-life cases illustrate the challenges in managing axPsA, emphasizing the importance of tailored therapies. Achieving precision in defining axPsA remains a formidable task, making detailed criteria essential for effective strategies and improving patient outcomes.

The aims of this study were to investigate the prevalence of dose reduction in patients with SLE treated with belimumab (BEL) in Spain, analyze treatment modalities, and determine impact on control of disease activity. Retrospective longitudinal and multicentre study of SLE patients treated with BEL. Data on disease activity, treatments and outcomes were recorded before and after reduction (6–12 months), and they were compared. A total of 324 patients were included. The dose was reduced in 29 patients (8.9%). The dosing interval was increased in 9 patients receiving subcutaneous BEL and in 6 patients receiving intravenous BEL. The dose per administration was reduced in 16 patients. Pre-reduction status was remission (2021 DORIS) in 15/26 patients (57.7%) and LLDAS in 23/26 patients (88.5%). After reduction, 2/24 patients (8.3%) and 3/22 patients (13.6%) lost remission at 6 months and 12 months, respectively (not statistically significant [NS]). As for LLDAS, 2/23 patients (8.7%) and 2/21 patients (9.5%) lost their status at 6 and 12 months, respectively (NS). Significantly fewer patients were taking glucocorticoids (GCs) at their 12-month visit, although the median dose of GCs was higher at the 12-month visit (5 [0.62–8.75] vs 2.5 [0–5] at baseline). Doses of BEL can be reduced with no relevant changes in disease activity—at least in the short term—in a significant percentage of patients, and most maintain the reduced dose. However, increased clinical or serologic activity may be observed in some patients. Consequently, tighter post-reduction follow-up is advisable.

To provide an overview on the current use of belimumab (BLM) in SLE patients in clinical practice and to examine its efficacy in terms of standardized outcomes, drug survival, as well as patient and safety profiles. A longitudinal retrospective multicentre cohort including SLE patients treated with BLM at 18 Spanish centers. Data was collected upon initiation of BLM, at 6 and 12 months after initiation, and at the last recorded visit. Changes in SLEDAI-2K, the proportion of patients who achieved LLDAS and DORIS 2021, and number of flares were compared between visits. Changes in damage, glucocorticoids use and employment status pre-BLM and post-BLM were also assessed. A total of 324 patients were included with a mean follow-up of 3.8 (±2.7) years. LLDAS was attained by 45.8%, 62% and 71% of patients, and DORIS by 24%, 36.2% and 52.5% on successive visits, respectively. Twenty-seven-point two percent of patients were in DORIS ≥ 50% of the visits and a 46% in LLDAS-50. Flares and number of flares were significantly lower one year after treatment with BLM and no changes in damage accrual were observed. Mean (±SD) prednisone dose was significantly reduced over time, with 70 (24%) patients discontinuing GC. Our study not only demonstrates belimumab´s efficacy in attaining treat-to-target goals in SLE patients, but also confirms its GC-sparing effect, and its prevention of flares and organ damage accrual.

Background: In 2017, belimumab (BEL) was approved in subcutaneous (SQ) administration. The effectiveness after switching from intravenous (IV) to SQ and patient satisfaction in daily clinical practice has not been studied. During the pandemic, patient follow-up and treatment were significantly affected, and some patients need a change from IV to SQ. Our aim was to evaluate daily clinical practice satisfaction to SQ BEL therapy in patients previously treated IV BEL. We hypothesized that SQ BEL in SLE patients previously treated with IV BEL was similar in effectiveness and conferred higher satisfaction. Methods: Observational, multicenter study, conducted in 7 reference centers in Catalonia. We included stable SLE patients (EULAR/ACR 2019) on treatment with SQ BEL and previous use of IV BEL (at least 3 months on IV BEL before switching). Since there are no well-validated tools for SQ BEL treatment satisfaction, we used RASQ-SQ, validated in patients with lymphoma who switched from IV Rituximab to SQ treatment, and modified for BEL treatment. Results: Twenty-seven patients were included. The more prevalent clinical manifestations observed were related to the skin and joints and the patients had a mean baseline SLEDAI of 2.96 (SD 2.4) and SLICC score of 0.67 (SD 0.88). The median time from treatment with IV BEL before switching to SQ was 21 months (range). 84% of patients reported confidence in SQ BEL. 85.2% felt that treatment with SQ BEL was convenient or very convenient. 85% felt they had gained time with the change. 89% would recommend the SQ injection to other patients. Disease activity (mean SLEDAI) and remission rates remain stable after switching. No major new adverse effects were reported. Conclusions: Overall satisfaction, satisfaction with via of administration, and satisfaction with the time taken to receive BEL were higher for SQ BEL treatment. A switching SQ strategy is a reasonable alternative for BEL patients.