Filgotinib as rheumatoid arthritis therapy.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation and progressive disability when inflammation cannot be sufficiently controlled. Despite treatment with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and biological DMARDs (bDMARDs), up to 30% of RA patients do not reach or fail to maintain a good response over time. The recent introduction of Janus kinase inhibitors (JAKis) has widened the rheumatologist's armamentarium. Filgotinib, a selective JAK1 inhibitor, has been approved by the European Medicines Agency (EMA) for treatment of RA. Phase II and III studies highlighted filgotinib safety and efficacy in RA patients naive to DMARDs or with inadequate response to csDMARDs and bDMARDs. Filgotinib is administered orally at 200 mg every day. For patients older than 75 years or with moderate to severe renal impairment, a dose of filgotinib 100 mg every day is recommended.

Systemic sclerosis interstitial lung disease evaluation: comparison between semiquantitative and quantitative computed tomography assessments.

The pulmonary fibrosis extent in systemic sclerosis (SSc) has a prognostic value. Chest Computed Tomography (CT) is the gold standard to detect an interstitial lung disease (ILD). Semi-quantitative scores and quantitative methods can estimate the ILD. The first ones have a considerable inter-intraobserver variability, while quantitative scores, based on distribution of lung attenuation parameters (also called CT indexes), can be obtained through expensive and not so user-friendly software. The aim of this work is to investigate whether a DICOM-viewer open-source software (OsiriX) can obtain CT indexes correlating with semi-quantitative scores. Sixty-three chest CTs of ILD-SSc patients were assessed with two semi-quantitative methods (visual extent and limited/extensive ILD grading) and then blindly processed with OsiriX to obtain the distribution parameters of lung attenuation (kurtosis, skewness and mean). Semiquantitative assessment and CT indexes were compared through the Spearman rank test and Mann-Whitney test. All CT indexes showed a statistically significant correlation of moderate degree with the visual extent semi-quantitative assessment (p-value less than 0.05). Skewness was the lung attenuation distribution parameter with the strongest correlation (r =-0.378, p-value = 0.0023). Moreover, CT indexes of patients with an extensive and limited disease were statistically different (p less than 0.01). CT indexes correlating with a radiological semi-quantitative ILD assessment can be obtained through OsiriX. CT indexes can be considered very helpful to discriminate patients with extensive and limited ILD.

Comparison of the Recent-Onset Arthritis Disability questionnaire with the Health Assessment Questionnaire disability index in patients with rheumatoid arthritis.

BACKGROUND: Physical disability in patients with rheumatoid arthritis (RA) is often assessed by questionnaires. We compared the Recent-Onset Arthritis Disability (ROAD) questionnaire with the Health Assessment Questionnaire (HAQ) disability index (DI) in a cohort of RA patients. The aim of this study was to obtain information on several aspects of construct validity of these measures. METHODS: A cross-sectional multicentre study was carried out among patients with RA who were attending hospital outpatient clinics. The patient group included 196 patients partially or not responding to disease modifying anti-rheumatic drugs. For the evaluation of the psychometric properties of the ROAD in comparison with HAQ-DI this population has been compared to another cohort of 247 outpatients with RA who were participating in a long-term observational study. All patients completed the ROAD and HAQ-DI. Additional comparator composite indices of disease activity were analysed. The ROAD structural validity was first assessed using exploratory factor analysis. Concurrent validity was analysed by Spearman's correlations and cross-tabulations. Discriminant validity to distinguish patients with active and non-active disease was assessed with receiver operating characteristic (ROC) curve analysis. For agreement analysis Bland and Altman plots were calculated. RESULTS: Factor analysis yielded a two-factor ROAD score that accounted for 68.74% of the explained variance in the questionnaire. The first factor, namely upper extremity function/activity daily living and work (ROAD-upper) accounted for 55.6% of the explained variance. The second factor, namely lower extremity function (ROAD-lower) accounted for 13.1% of the explained variance. Significant correlations were found between the scores of the ROAD and the other clinical variables with a high ability to measure pain and disease activity, supporting the concept of convergent construct validity. The discriminatory power of both questionnaires to assess inactive and active RA patients was good, without significant difference. CONCLUSIONS: ROAD is a good alternative to the HAQ-DI for the assessment of physical disability in RA. Use of the ROAD makes it easier and less costly to collect data and reduces the burden on RA patients and should be applied in both clinical trials and routine clinical care settings.

Psychometric properties of an index of three patient reported outcome (PRO) measures, termed the CLinical ARthritis Activity (PRO-CLARA) in patients with rheumatoid arthritis. The NEW INDICES study.

OBJECTIVES: To evaluate the psychometric properties of an index based on 3 patient reported outcomes measures, termed PRO-CLinical ARthritis Activity (PRO-CLARA), in order to facilitate rapid and easy rheumatoid arthritis (RA) activity assessment in daily routine. METHODS: 196 patients partially or not responding to disease modifying anti-rheumatic drugs (DMARDs), consented to participate in a multicentre cross-sectional study. For the evaluation of the psychometric properties of the PRO-CLARA, this population has been compared to another cohort of 247 outpatients with RA who were participating in a long-term observational study and who satisfying minimal disease activity and remission definitions. All patients completed the PRO-CLARA, combining patient's physical function, self-administered tender joint count and perception of global health status into a single measure of disease activity. Additional comparator composite indices were analysed. Internal consistency was assessed with Cronbach's alpha coefficient. A confirmatory factor analysis was carried out to test factor structure. Concurrent validity was analyzed using Spearman's correlations and cross-tabulations. Discriminant validity to distinguish patients with active and non-active disease was assessed with receiver operating characteristic (ROC) curve analysis. For agreement analysis, kappa statistics were calculated. RESULTS: In testing for internal consistency, we found that Cronbach's alpha for the PRO-CLARA was 0.893, indicating high reliability. PRO-CLARA proved to be significantly correlated to established RA activity assessment tools. The area under ROC curve of the PRO-CLARA gives identical results to those provided by other comparator indices. CONCLUSIONS: The study showed satisfactory psychometric properties of the PRO-CLARA.

[Pulmonary hypertension in rheumatic diseases]. / L'ipertensione polmonare nelle malattie reumatiche.

In rheumatic diseases (RD) pulmonary hypertension (PH) may result by either direct damage of the pulmonary arteries (isolated PH) or pulmonary interstitial fibrosis and other causes. PH is an important cause of morbidity and mortality in systemic sclerosis in which it is more frequently isolated in the limited cutaneous variant and secondary to interstitial fibrosis in the diffuse type. In isolated PH the main histopathological finding is an occlusive arteriopathy. The role of recurrent vasospasm ("lung Raynaud's phenomenon") is still being debated. In systemic lupus erythematosus, although uncommon, PH is being increasingly reported and may recognize multiple etiological factors including vasoconstriction, vasculitis, in-situ pulmonary thrombosis or chronic recurrent thromboembolism. PH may be a severe and often fatal complication of mixed connective tissue disease and dermato/polymyositis. PH may also be diagnosed in patients with rheumatoid arthritis, primary Sjögren's syndrome and primary antiphospholipid syndrome. Doppler echocardiography is the technique of choice for the evaluation of PH because it is nonivasive and allows serial determinations of the arterial pulmonary pressure. The therapy of PH associated with RD includes corticosteroids, immunosuppressive drugs, calcium-antagonists, ACE-inhibitors, anticoagulants, O2, prostacyclin or its stable analogue, iloprost. Carefully selected patients may benefit from single lung or heart-lung transplantation.