Rate of severe and fatal infections in a cohort of patients with interstitial lung disease associated with rheumatoid arthritis: a multicenter prospective study.

Objective: To describe severe infection, foci of infection, microorganisms, associated factors, and impact on mortality in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Patients and methods: The study was based on a multicenter prospective cohort of patients with RA-ILD followed up from 2015 to 2023. The main outcome measures were incident severe infection and fatal infection. We evaluated infectious foci, etiologic agents, vaccination status, variables associated with lung function, and clinical-therapeutic variables in RA. The incidence rate (IR) for infection and mortality was calculated per 100 person-years, and 3 multivariate models were constructed to explore factors associated with infection. Results: We followed up 148 patients with RA-ILD for a median 56.7 months (699.3 person-years). During this period, 142 patients (96%) had at least 1 infection. A total of 368 infectious episodes were recorded, with an IR of 52.6 per 100 person-years. Of the 48 patients who died, 65% did so from infection. Respiratory infections were the most common first infection (74%), infection overall (74%), and fatal infection (80%) and were caused mostly by SARS CoV-2, Streptococcus pneumoniae, Pseudomonas aeruginosa, and influenza A virus. The factors associated with an increased risk of infection and death in patients with RA-ILD were age, inflammatory activity, and therapy with corticosteroids and immunosuppressants. Conclusion: Patients with RA-ILD have a high risk of serious infection, especially respiratory infection. Infection develops early, is recurrent, and is frequently fatal. The presence of associated factors such as advanced age, joint inflammation, and treatment highlight the importance of integrated and preventive medical care.

Analysis of comorbidity in rheumatoid arthritis-associated interstitial lung disease: a nested case-cohort study.

OBJECTIVES: To describe comorbid conditions in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and to analyze factors associated with multimorbidity. METHODS: Nested case-cohort study of 2 prospective cohorts: one with RA-ILD (cases) and another with RA but not ILD (controls). The cohorts were matched for age, sex, and time since diagnosis. Multimorbidity was defined as the co-occurrence of 2 or more chronic diseases, in addition to RA and ILD. We evaluated the comorbid conditions included in the Charlson Comorbidity Index, cardiovascular risk factors, neuropsychiatric conditions, and other frequent conditions in RA. We also recorded clinical-laboratory variables, inflammatory activity according to the 28-joint Disease Activity Score, C-reactive protein (CRP), physical function, and pulmonary function. We performed 2 multivariate analyses to identify factors associated with multimorbidity in RA and RA-ILD. RESULTS: The final study population comprised 110 cases and 104 controls. Multimorbidity was more frequent among cases than controls (80 [72.7] vs 60 [57.7]; p = 0.021). In both groups, multimorbidity was associated with ILD (OR [95% CI] 1.92 [1.03-3.59]; p = 0.039), age (OR [95% CI] 1.05 [1.01-1.08]; p = 0.004), CRP (OR [95% CI] 1.16 [1.05-1.29]; p = 0.003), and erosions (OR [95% CI] 1.05 [1.01-1.08]; p = 0.004); in the cases, it was associated with CRP (OR [95% CI] 1.17 [1.01-1.35]; p = 0.027), anti-citrullinated peptide antibody (OR [95% CI] 1.23 [1.14-13.02]; p = 0.049), and forced vital capacity (OR [95% CI] 0.79 [0.96-0.99]; p = 0.036). CONCLUSION: In patients with RA, multimorbidity was associated with ILD, systemic inflammation, and advanced age.

Does expert opinion match the definition of lupus low disease activity state? Prospective analysis of 500 patients from a Spanish multicentre cohort.

OBJECTIVES: To apply the lupus low disease activity state (LLDAS) definition within a large cohort of patients and to assess the agreement between the LLDAS and the physician's subjective evaluation of lupus activity. METHODS: We conducted a cross-sectional analysis of a prospective multicentre study of SLE patients. We applied the LLDAS and assessed whether there was agreement with the clinical status according to the physician's opinion. RESULTS: A total of 508 patients [92% women; mean age 50.4 years (s.d. 3.7)] were recruited and 304 (62.7%) patients were in the LLDAS. According to physician assessment, 430 (86.1%) patients were classified as remission or low activity. Overall agreement between both evaluations was 71.4% (95% CI: 70.1, 70.5) with a Cohen's κ of 0.3 [interquartile range (IQR) 0.22-0.37]. Most cases (96.1%) in the LLDAS were classified as remission or low activity by the expert. Of the patients who did not fulfil the LLDAS, 126 (70.4%) were classified as having remission/low disease activity. The main reasons for these discrepancies were the presence of new manifestations compared with the previous visit and a SLEDAI 2K score >4, mainly based on serological activity. CONCLUSIONS: Almost two-thirds of SLE patients were in the LLDAS. There was a fair correlation between the LLDAS and the physician's evaluation. This agreement improves for patients fulfilling the LLDAS criteria. The discordance between both at defining lupus low activity, the demonstrated association of the LLDAS with better outcomes and the fact that the LLDAS is more stringent than the physician's opinion imply that we should use the LLDAS as a treat-to-target goal.

Safety and Effectiveness of Abatacept in a Prospective Cohort of Patients with Rheumatoid Arthritis-Associated Interstitial Lung Disease.

OBJECTIVE: To prospectively evaluate the safety and efficacy profile of abatacept in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). METHODS: We performed a prospective observational multicenter study of a cohort of patients with RA-ILD treated with abatacept between 2015 and 2021. Patients were evaluated using high-resolution computed tomography and pulmonary function tests at initiation, 12 months, and the end of follow-up. The effectiveness of abatacept was evaluated based on whether ILD improved, stabilized, progressed, or was fatal. We also evaluated factors such as infection, hospitalization, and inflammatory activity using the 28-joint Disease Activity Score with the erythrocyte sedimentation rate (DAS28-ESR). Cox regression analysis was performed to identify factors associated with progression of lung disease. RESULTS: The study population comprised 57 patients with RA-ILD treated with abatacept for a median (IQR) of 27.3 (12.2-42.8) months. Lung disease had progressed before starting abatacept in 45.6% of patients. At the end of follow-up, lung disease had improved or stabilized in 41 patients (71.9%) and worsened in 13 (22.8%); 3 patients (5.3%) died. No significant decreases were observed in forced vital capacity (FVC) or in the diffusing capacity of the lung for carbon monoxide (DLCO).The factors associated with progression of RA-ILD were baseline DAS28-ESR (OR [95% CI], 2.52 [1.03-3.12]; p = 0.041), FVC (OR [95% CI], 0.82 [0.70-0.96]; p = 0.019), and DLCO (OR [95% CI], 0.83 [0.72-0.96]; p = 0.018). Only 10.5% of patients experienced severe adverse effects. CONCLUSION: Pulmonary function and joint inflammation stabilized in 71% of patients with RA-ILD treated with abatacept. Abatacept had a favorable safety profile.

Calcineurin and Systemic Lupus Erythematosus: The Rationale for Using Calcineurin Inhibitors in the Treatment of Lupus Nephritis.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a broad spectrum of clinical presentations that can affect almost all organ systems. Lupus nephritis (LN) is a severe complication that affects approximately half of the systemic erythematosus lupus (SLE) patients, which significantly increases the morbidity and the mortality risk. LN is characterized by the accumulation of immune complexes, ultimately leading to renal failure. Aberrant activation of T cells plays a critical role in the pathogenesis of both SLE and LN and is involved in the production of inflammatory cytokines, the recruitment of inflammatory cells to the affected tissues and the co-stimulation of B cells. Calcineurin is a serine-threonine phosphatase that, as a consequence of the T cell hyperactivation, induces the production of inflammatory mediators. Moreover, calcineurin is also involved in the alterations of the podocyte phenotype, which contribute to proteinuria and kidney damage observed in LN patients. Therefore, calcineurin inhibitors have been postulated as a potential treatment strategy in LN, since they reduce T cell activation and promote podocyte cytoskeleton stabilization, both being key aspects in the development of LN. Here, we review the role of calcineurin in SLE and the latest findings about calcineurin inhibitors and their mechanisms of action in the treatment of LN.

Associated factors to serious infections in a large cohort of juvenile-onset systemic lupus erythematosus from Lupus Registry (RELESSER).

OBJECTIVE: To assess the incidence of serious infection (SI) and associated factors in a large juvenile-onset systemic lupus erythematosus (jSLE) retrospective cohort. METHODS: All patients in the Spanish Rheumatology Society Lupus Registry (RELESSER) who meet ≥4 ACR-97 SLE criteria and disease onset <18 years old (jSLE), were retrospectively investigated for SI (defined as either the need for hospitalization with antibacterial therapy for a potentially fatal infection or death caused by the infection). Standardized SI rate was calculated per 100 patient years. Patients with and without SI were compared. Bivariate and multivariate logistic and Cox regression models were built to calculate associated factors to SI and relative risks. RESULTS: A total of 353 jSLE patients were included: 88.7% female, 14.3 years (± 2.9) of age at diagnosis, 16.0 years (± 9.3) of disease duration and 31.5 years (±10.5) at end of follow-up. A total of 104 (29.5%) patients suffered 205 SI (1, 55.8%; 2-5, 38.4%; and ≥6, 5.8%). Incidence rate was 3.7 (95%CI: 3.2-4.2) SI per 100 patient years. Respiratory location and bacterial infections were the most frequent. Higher number of SLE classification criteria, SLICC/ACR DI score and immunosuppressants use were associated to the presence of SI. Associated factors to shorter time to first infection were higher number of SLE criteria, splenectomy and immunosuppressants use. CONCLUSIONS: The risk of SI in jSLE patients is significant and higher than aSLE. It is associated to higher number of SLE criteria, damage accrual, some immunosuppressants and splenectomy.

Classification of Systemic Lupus Erythematosus: Systemic Lupus International Collaborating Clinics Versus American College of Rheumatology Criteria. A Comparative Study of 2,055 Patients From a Real-Life, International Systemic Lupus Erythematosus Cohort.

OBJECTIVE: The new Systemic Lupus International Collaborating Clinics (SLICC) 2012 classification criteria aimed to improve the performance of systemic lupus erythematosus (SLE) classification over the American College of Rheumatology (ACR) 1997 criteria. However, the SLICC 2012 criteria need further external validation. Our objective was to compare the sensitivity for SLE classification between the ACR 1997 and the SLICC 2012 criteria sets in a real-life, multicenter, international SLE population. METHODS: We conducted a cross-sectional observational study of patients with a clinical diagnosis of SLE followed at the participating rheumatology centers and registered in the Portuguese and Spanish national registries. The sensitivity of the 2 classification sets was compared using McNemar's test. The sensitivity of ACR 1997 and SLICC 2012 was further examined in 5 subgroups, defined according to disease duration. RESULTS: We included 2,055 SLE patients (female 91.4%, white 93.5%, mean ± SD age at disease onset 33.1 ± 14.4 years, mean ± SD age at SLE diagnosis 35.3 ± 14.7 years, and mean ± SD age at the time of the study 47.4 ± 14.6 years) from 17 centers. The sensitivity for SLE classification was higher with the SLICC 2012 than with the ACR 1997 (93.2% versus 85.6%; P < 0.0001). Of 296 patients not fulfilling the ACR 1997, 62.8% could be classified with the SLICC 2012. The subgroup of patients with ≤5 years since disease onset presented the largest difference in sensitivity between the SLICC 2012 and the ACR 1997 (89.3% versus 76.0%; P < 0.0001); this difference diminished with longer disease duration, and it was no longer significant for patients with >20 years of disease duration. CONCLUSION: The SLICC 2012 criteria were more sensitive than the ACR 1997 criteria in real-life clinical practice in SLE. The SLICC 2012 criteria may allow patients to be classified as having SLE earlier in the disease course.