Helena Andersson

Long-term experience with rituximab in anti-synthetase syndrome-related interstitial lung disease

OBJECTIVE To retrospectively evaluate the efficacy and safety of rituximab (Rtx) treatment in patients with anti-synthetase syndrome (ASS) and severe interstitial lung disease (ILD). METHODS Patients with severe ILD and >12 months follow-up post-Rtx were identified from the Oslo University Hospital ASS cohort (n = 112). Clinical data, including pulmonary function tests (PFTs), were retrospectively collected from medical reports. Extent of ILD pre-, and post-Rtx was scored on thin-section high-resolution CT (HRCT) images and expressed as a percentage of total lung volume. Muscle strength was evaluated by manual muscle testing of eight muscle groups (MMT8). RESULTS Altogether, 34/112 ASS patients had received Rtx; 24/34 had severe ILD and >12 months follow-up post-Rtx (median 52 months). In these 24 patients, the median percentage of predicted forced vital capacity, forced expiratory volume in 1 s (FEV1) and diffusing capacity of the lungs for carbon monoxide (DLCO) increased by 24%, 22% and 17%, respectively, post-Rtx. Seven patients (all with disease duration <12 months and/or acute onset/exacerbation of ILD) had >30% improvement in all three PFTs. HRCT analysis showed a median 34% reduction in ILD extent post-Rtx. MMT8 score increased post-Rtx. During follow-up, 7/34 (21%) Rtx-treated ASS patients died; 6/7 deaths were related to infections. The mortality rate in the Rtx-treated group was comparable to that of the remaining ASS cohort (25/78 deceased; 32%). CONCLUSION This study, which included 24 Rtx-treated ASS patients with severe ILD, reports improved PFTs after a median 52 months follow-up post-Rtx. The best outcome was observed in patients with a disease duration <12 months and/or acute onset/exacerbation of ILD. The study indicates that Rtx could be a treatment option for selected ASS patients, but infections should be given attention.

The EuroMyositis registry: an international collaborative tool to facilitate myositis research.

Aims The EuroMyositis Registry facilitates collaboration across the idiopathic inflammatory myopathy (IIM) research community. This inaugural report examines pooled Registry data. Methods Cross-sectional analysis of IIM cases from 11 countries was performed. Associations between clinical subtypes, extramuscular involvement, environmental exposures and medications were investigated. Results Of 3067 IIM cases, 69% were female. The most common IIM subtype was dermatomyositis (DM) (31%). Smoking was more frequent in connective tissue disease overlap cases (45%, OR 1.44, 95% CI 1.09 to 1.90, p=0.012). Smoking was associated with interstitial lung disease (ILD) (OR 1.32, 95% CI 1.06 to 1.65, p=0.013), dysphagia (OR 1.43, 95% CI 1.16 to 1.77, p=0.001), malignancy ever (OR 1.78, 95% CI 1.36 to 2.33, p<0.001) and cardiac involvement (OR 2.40, 95% CI 1.60 to 3.60, p<0.001). Dysphagia occurred in 39% and cardiac involvement in 9%; either occurrence was associated with higher Health Assessment Questionnaire (HAQ) scores (adjusted OR 1.79, 95% CI 1.43 to 2.23, p<0.001). HAQ scores were also higher in inclusion body myositis cases (adjusted OR 3.85, 95% CI 2.52 to 5.90, p<0.001). Malignancy (ever) occurred in 13%, most commonly in DM (20%, OR 2.06, 95% CI 1.65 to 2.57, p<0.001). ILD occurred in 30%, most frequently in antisynthetase syndrome (71%, OR 10.7, 95% CI 8.6 to 13.4, p<0.001). Rash characteristics differed between adult-onset and juvenile-onset DM cases (‘V’ sign: 56% DM vs 16% juvenile-DM, OR 0.16, 95% CI 0.07 to 0.36, p<0.001). Glucocorticoids were used in 98% of cases, methotrexate in 71% and azathioprine in 51%. Conclusion This large multicentre cohort demonstrates the importance of extramuscular involvement in patients with IIM, its association with smoking and its influence on disease severity. Our findings emphasise that IIM is a multisystem inflammatory disease and will help inform prognosis and clinical management of patients.

Pulmonary Involvement in the Antisynthetase Syndrome: A Comparative Cross-sectional Study.

Objective. Interstitial lung disease (ILD) is a major component of the antisynthetase syndrome, but quantitative data on longterm pulmonary outcome in antisynthetase syndrome are limited. In this study, the main aims were to compare pulmonary function tests (PFT) and the 6-min walking distance (6MWD) between patients with antisynthetase syndrome and healthy sex- and age-matched controls, to evaluate the extent of ILD by lung high-resolution computed tomography (HRCT), and to assess correlations between PFT measures and ILD extent. Methods. Concurrent PFT and 6MWD were performed in 68 patients with antisynthetase syndrome and their individually matched controls. Additionally, in the patients, the extent of ILD was determined in 10 HRCT sections, expressed as percentage of total lung volumes. Results. Median disease duration in the antisynthetase syndrome cohort was 71 months. Compared with the matched controls, the patients with antisynthetase syndrome had mean 28%, 27%, and 53% lower absolute values of forced vital capacity (FVC), forced expiratory volume in 1 s, and DLCO (p < 0.001). Mean difference in 6MWD between patients and controls was 116 m (p < 0.001). Median extent of ILD by HRCT was 20% (range 0–73) and correlated with FVC and DLCO. Pulmonary outcome did not differ between Jo1 and non-Jo1 subsets. Conclusion. To our knowledge, this study is the first to demonstrate a highly significant difference in PFT between patients with antisynthetase syndrome with 6 years of followup and healthy controls. DLCO displayed the highest difference with mean 53% lower value in the patients. FVC and DLCO correlated significantly with ILD extent, indicating these variables as appropriate outcome measures in antisynthetase syndrome–associated ILD.

Response to: 'Antisynthetase syndrome or what else? Different perspectives indicate the need for new classification criteria' by Cavagna et al

We thank Cavagna et al 1 for their thoughtful analysis relating to our recent publication.2 Several important points are raised, many of which we also referred to. It is of great interest and reassurance that the demographics and clinical features of antisynthetase syndrome (ASS) are broadly similar between the AENEAS (American and European NEtwork of Anti-Synthetase syndrome) and EuroMyositis cohorts. Clearly the frequency of interstitial lung disease and arthritis differs due to the sources of case ascertainment. This highlights …

FRI0250 Self Reported Gastrointestinal Tract Symptoms in Systemic Sclerosis: Experience from A Large Consecutive Cohort

Background Gastrointestinal tract (GIT) involvement in systemic sclerosis (SSc) is common, occurring in 50–90% of the patients (1). However, there is limited knowledge of self reported GIT symptoms affecting patients in daily life. Objectives To describe frequency and severity of self reported gastrointestinal symptoms in a large SSc cohort and evaluate possible correlations between special clinical characteristics and GIT-symptoms. Methods Patients from the The Norwegian Systemic Connective Tissue Disease and Vasculitis Registry (NOSVAR) who fulfilled the 2013 ACR/EULAR SSc criteria were included (N=245)). The patients completed the UCLA SCTC GIT 2.0 questionnaire which comprises seven clinical symptoms; Reflux, distention/bloating, diarrhea, fecal soilage, social functioning, emotional well-being and constipation. All variables are scored from better to worse in health related quality of life (HRQL) with a mean total score of 2.8. In addition we used the visual analogue scale on intestinal problems (VAS-GIT) of the Scleroderma Health Assessment Questionnaire (SHAQ) with a maximum score of 3. Disease duration was defined as time from diagnosis to the completion of the questionnaires. Possible correlations were tested by Spearmans correlation coefficient. Results Patient characteristics and frequencies of the different GIT symptoms are presented in Table 1. Distention bloating, reflux and diarrhea were the most frequent symptoms reported (80%, 69% and 61%, respectively. The least reported symptom was fecal soilage (16%) (Figure 1). Mean (SD) total GIT score was 0.42 (0.41), indicating mild symptoms. The seven subscales ranged from mean (SD) 0.22 (0.55) for fecal soilage to mean (SD) 0.95 (0.50) for distention/bloating. Mean (SD) VAS-GIT score was 0.33 (0.37) and correlated strongly with the mean total UCLA-GIT score (0.667, p<0.001). Female sex and disease duration correlated weakly with mean total UCLA-GIT score (r=-.234, r=199, respectively), as did positive anticentromere-antibody (r=.229).No correlation was found between mean total UCLA-GIT score and subset of SSc, interstitial lung disease, pulmonary hypertension, digital ulcers, Rodnan skin score or Raynaud.Table 1 Clinical characteristics Female sex, n (%) 210 (86) Age, yrs, mean (SD) 53 (14) Diffuse, n (%) 57 (24) Limited, n (%) 178 (73) Sine, n (%) 10 (4) Disease duration, yrs, median (25th, 75th centile) 5.8 (2.1, 10.7) Anti-SCL70 antibody, n (%) 32/208 (15) Anticentromere antibody, n (%) 133/223 (60)Figure 1 Conclusions This study describes a high frequency of self-reported gastrointestinal symptoms in systemic sclerosis patients classified as mild to moderate symtoms. Positive anticentromere-antibody, disease duration and female sex had a minor impact on mean total UCLA-GIT score. The correlation between mean total UCLA-GIT score and the VAS-GIT score of the SHAQ was highly significant indicating a good conformity between the tests. References Forbes A, Marie I: Gastrointestinal complications: the most frequent internal complications of systemic sclerosis. Rheumatology (Oxford) 2009;48 Suppl 3:36–9. Disclosure of Interest None declared

SAT0457 A Cross-Sectional Case-Control Study of Pulmonary Function in the Anti-Synthetase Syndrome

Background Interstitial lung disease (ILD), myositis and anti-aminoacyl tRNA synthetase (aaRS) antibodies are the key disease components of the Antisynthetase syndrome (ASS). Several studies indicate that the ILD in ASS often causes restrictive ventilation impairment, but quantitative data on lung function and physical capacity are largely missing. Objectives To assess pulmonary function tests (PFT) and six minutes walking distance (6MWD) in a cohort of ASS-patients and compare the results with healthy controls individually matched for sex and age. Methods The Oslo University Hospital (OUH) ASS cohort is a single referral center cohort that includes 97 patients identified with positive aaRS antibodies, ILD and/or myositis in the period from 1994 to 2011. The current, cross-sectional study included 68 of the 71 ASS patients in the cohort that were alive by September 2011 (the last three patients refused participation). Sex and age-matched healthy controls were randomly collected from the National People Register of Norway in an 1:1 proportion (N=67). Thus, 68 patients and 67 controls were eligible to perform 6MWD and PFT. PFT included forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and diffusing capacity of the lung for Carbon monoxide (DLCO). The study was performed during the period of Sept 2011-June 2014 and approved by the regional committee of health and medical research ethics in South-East Norway. Paired samples T-test was used for statistical significance (p<0.05). Results The study cohort included 45 female and 23 male ASS patients (53 with anti-Jo-1 antibodies, 6 anti-PL-7 positive and 9 anti-PL-12 positive) with mean age 47 years at diagnosis. The PFT and 6MWD was performed median 71 months after diagnosis (6-362). Altogether, 66/68 ASS patients had a clinical ILD diagnosis, and 50/68 had myositis. Mean FVC in the ASS patients was 2.90 l compared to 3.73 l in the control group, a mean difference of 0.83 l (29%) (p<0.000). In the patients, the mean FEV1 was 2.29 l; 0.63 l (28%) lower than in the controls (p<0.000). Mean DLCO in the patients was 5.56 mmol/kPa.min, compared to 8.40 mmol/kPa.min in the controls, a mean difference of 2.84 mmol/kPa.min (51%) (p<0.000). The ASS patients had a mean 6MWD of 543 meters, the corresponding value in the controls was 659 m, giving a difference of 116 m (21%) (p<0.000). Conclusions The data from this cross-sectional, case-controlled study demonstrates a highly significant difference in pulmonary function and 6MWD between ASS patients with median 71 months disease duration and matched healthy controls. The highest difference in PFT was seen in DLCO with 51% lower mean value in the ASS-group; possibly indicating that the ILD in ASS involves pulmonary vessel pathology. The study confirms the severity of pulmonary involvement in ASS and highlights the need for effective treatment strategies in this patient group. Disclosure of Interest None declared