Clinical and experimental rheumatology最新文献

Objectives: To describe drug survival, safety and treatment response in sarcoidosis patients treated with abatacept or tofacitinib in routine care.

Methods: We identified 41 sarcoidosis patients treated with abatacept and 12 patients treated with tofacitinib. Of the patients treated with tofacitinib 83% had previously been treated with abatacept. Drug survival and reasons for discontinuation of treatment was investigated. Treatment response was evaluated at least once within the first 6 months of treatment by at least one trained clinician and classified as responder or non-responder. No direct comparison of drugs was made.

Results: Median (range) disease duration was 3.5 (1-27) and 3 (1-16) years for abatacept and tofacitinib. The patients had previously received a median of 1 DMARD and 1 biological DMARD in both groups. Nearly all patients had been treated with at least one TNFi (95%/92 %). After 6 months, 90% (95%CI 85-90%) of the 41 patients in the abatacept group and 89% (79-99%) of the 12 patients in the tofacitinib group-maintained treatment. At 12 months, it was 80% (73-87%) and 74% (58-90%). No serious adverse events were recorded. For abatacept and tofacitinib 71% and 67% of patients were characterised as responders. In both treatment groups, there was a significant reduction in prednisolone dosage and levels of soluble IL2-receptor at all time points.

Conclusions: Sarcoidosis patients treated with abatacept and tofacitinib had long drug survival, achieved high response rates. Both drugs represent good and safe therapeutic options in sarcoidosis patient's refractory to previous TNFi therapy.

Objectives: To determine the effects of dose reduction of rituximab (RTX) on rheumatoid arthritis (RA) disease activity in clinical practice.

Methods: Retrospective cohort study of RA patients using RTX, in stable low disease activity (i.e. Disease Activity Score 28-joint count CRP (DAS28-CRP) ≤3.5 for ≥6 consecutive months) and ≥2 DAS28-CRP measurements. We identified three treatment periods: 1) full dose RTX, 2) RTX dose reduction, and 3) stable RTX dose (and interval) after tapering. Linear mixed-model analysis was used to estimate mean DAS28-CRP during these periods. Rituximab use was assessed as the median percentage of the RTX Daily Defined Dose (%DDD) per period, with 1 x 1000 mg/6 months as reference.

Results: 387 patients were included in the cohort with a median of 8 DAS28-CRP measurements (Q1-Q3:4-13) available per patient and median follow-up time of 44 months (Q1-Q3: 23-76). 299 patients tapered RTX and entered period 2 at least once, of whom 226 also entered period 3. Mean DAS28-CRP were 2.37 (95% CI: 2.29, 2.44) for period 1, 2.33 (95% CI: 2.25, 2.40) for period 2, and 2.27 (95% CI: 2.18, 2.35) for period 3, the latter significantly lower compared to period 1 (p=0.025). %DDD for the three time periods were 96%, 57% and 49%, respectively.

Conclusions: Dose reduction of RTX in clinical practice is effective for many RA patients and leads to relevant dose reduction. Together with other previously proven benefits of ultra-low dose RTX, wider implementation of ultra-low dose RTX in RA patients should be considered.

Objectives: Sarcoidosis is a clinically heterogenous disease. The objective of this study is the identification of clinical phenotypes using cluster analysis.

Methods: A model-based clustering relaying on 19 clinical variables was performed in a retrospective cohort of 342 sarcoidosis patients, diagnosed and followed-up from 1999 to 2019 in a tertiary hospital at Northern Spain. Chi-square test and ANOVA were used to compare categorical and continuous variables among groups. Two-sample t-tests and the partition of Pearson's chi-square statistic were used in pairwise comparisons. The Wasfi severity score was calculated and compared among clusters.

Results: Cluster analysis identified five groups: C1 (16.1%), C2 (14.3%), C3 (24.3%), C4 (5.0%), and C5 (40.4%). Lung involvement was predominant, ranging from 55.1% (C2) to 100% (C1 and C4). Extrapulmonary involvement was significantly higher in C2 (96.4%) and C3 (98.0%). A significant lower FEV1 percent predicted was detected in C5 (90.5±21.8) versus C1 (102.0±22.9), C3 (102.3±17.6) and C4 (105.8±20.8). The cluster 5 had a lower FVC percent predicted (96.6±18.9) than others, ranging from 108.1±18.0 (C3) to 111.5±21.7 (C4). The prescription of systemic glucocorticoids and non-corticosteroid immunosuppressants was higher in the clusters 1, 3 and 5. Chronicity rates were higher in C3 (31.3%) and C5 (32.6%) compared to C1 (9.1%) and C4 (0%), as well as the Wasfi severity score values.

Conclusions: Five phenotypes with different clinical and prognostic characteristics are proposed in our study. Cluster analysis can be a useful tool for identifying clinical patterns in a disease as heterogeneous as sarcoidosis and optimising its management.

Objectives: The early diagnosis of seronegative rheumatoid arthritis (SNRA), characterised by the absence of rheumatoid factor and anti-citrullinated antibody, involves a greater challenge compared to seropositive RA (SPRA). This study aimed to assess the discriminatory potential of anti-human IgG hinge antibodies (AHAs) for patients with early SNRA.

Methods: DMARDs-naive patients with SPRA (n=43), SNRA (n=21), and non-RA (n=49), with disease duration < 2 years, were included. Antigens comprised IgG1 or IgG4 F(ab')2 cleaved by pepsin or MMP-3 and their hinge peptide analogues. Eight IgG anti-hinge antibodies (AHAs) against these antigens were measured in sera from the patients and 58 healthy controls (HCs) using ELISA. Serum CRP and MMP-3 levels, and clinical disease activity index (CDAI), were obtained from medical records. The area under the curve (AUC) obtained from logistic regression and receiver operating characteristic curve analyses were used as a discriminant indicator.

Results: The levels of the IgG AHAs were as follows: SPRA≥SNRA≈non-RA>HC. None of the AHAs were effective in discriminating SNRA from non-RA. However, the combination of MMP-3 and AHAs against IgG4 hinge peptide analogues demonstrated the utility (AUC=0.94). Furthermore, combination of MMP-3, AHAs against IgG1 hinge peptide analogues and CDAI maximally exerted discriminatory power (AUC=0.997).

Conclusions: Specific AHAs in combination with MMP-3 and CDAI are potentially useful to discriminate SNRA from non-RA.

Objectives: Methotrexate (MTX) is the most used drug to treat children and adults with arthritis and its use is burdened by adverse effects. The MTX intolerance severity score (MISS) was developed in English to identify patients who are intolerant to MTX. The aim of this study was to translate and validate the MISS in Italian.

Methods: The Italian version of the MISS was developed following the "guidelines for process of cross-cultural adaptation of self-reported measures". The Italian version of the MISS was validated in 125 patients with juvenile idiopathic arthritis (JIA) followed at the Rheumatology Unit of Bambino Gesù Children Hospital. We assessed the construct validity and calculated the internal consistency of the Italian MISS. We performed ROC analysis to assess the overall performance of the Italian MISS.

Results: We translated and adapted the MISS to the Italian language. The Italian MISS showed a very good internal consistency as shown by a Cronbach α of 0.87 (95% CI, 0.84-0.90) and a composite reliability of 0.89 (95% CI, 0.83-0.91).The Cohen's κ was 0.81 (95% CI, 0.71-0.91), suggesting a very good construct validity. The ROC analysis showed an area under the curve (AUC) of 0.97 (95% CI, 0.93-0.99). A threshold of 6 to define intolerant patients, showed a sensitivity of 98.3% and specificity of 81.2%.

Conclusions: We developed the Italian version of the MISS and showed its validity and reliability to identify patients intolerant to MTX in clinical practice and in a research setting.

Objectives: In recent years, the distinct clinical presentations and elevated mortality rates of various subtypes of juvenile idiopathic arthritis (JIA) with pulmonary involvement have garnered significant attention. This study aimed to elucidate the clinical characteristics of pulmonary involvement in patients with JIA to improve clinicians' knowledge.

Methods: This single-centre retrospective study analysed the baseline data, treatment options, follow-up of sixty patients of JIA with pulmonary involvement in China. Patients with interstitial lung disease (ILD) were further classified in accordance with the 2013 American Thoracic Society/European Respiratory Society International multidisciplinary consensus on idiopathic interstitial pneumonia.

Results: Sixty patients (5.03%) with JIA were complicated with pulmonary involvement. The highest subtype was systemic JIA (sJIA, 63.3%), followed by rheumatoid factor (RF)-positive polyarthritis (pJIA, 25.0%). The incidence of macrophage activation syndrome (MAS) was 21.6%. The most common diagnosis was ILD (90%). Respiratory symptoms/signs were initially experienced by 61.7% of the patients, and respiratory support was required by 21.7%. High-resolution CT classification of sJIA revealed non-specific interstitial pneumonia (NSIP) and organising pneumonia. High-resolution CT classification of pJIA was NSIP and usually interstitial pneumonia (UIP). Patients were treated with NSAIDs, along with glucocorticoids, DMARDs, and biological agents. The survival rates after 1 and 5 years were approximately 93.3% and 90.0%, respectively.

Conclusions: Patients with JIA with pulmonary involvement present with early onset, high mortality rate. JIA patients should undergo physical examination thoroughly and high-resolution CT scans, lung function tests for evaluating and monitoring the occurrence and development of pulmonary involvement in early stages to improve prognosis.