DAH may present without hemoptysis and requires an early bronchoscopy to confirm the diagnosis and exclude infection. Other characteristics could be included in the abstract which are relevant to the paper. (relation between mortality, dialysis, ventilation, etc.).

Objective Most reports on serious infections (SI) in rheumatoid arthritis (RA) patients treated with biological disease-modifying antirheumatic drugs (bDMARDs) are from the USA and Western Europe. Data from other regions are largely missing. We report data from South American countries with different backgrounds and health-care systems but similar registries. Methods We merged 2010-2016 data from two registries, BIOBADABRASIL (Brazil) and BIOBADASAR (Argentina), which share the same protocol, online platform and data monitoring process. Patients with active RA were included when they began the first bDMARD or a conventional synthetic DMARD (csDMARD, control group). The SI incidence rate (IR) per 1000 patient/ years and adjusted IR ratio (aIRR) were estimated for bDMARDs and csDMARDs. Results Data were analysed for 3717 RA patients with an exposure of 13,380 patient/years. The 2591 patients treated with bDMARDs (64% tumour necrosis factor-α inhibitors (TNFi)) had a follow-up of 9300 years, and the 1126 treated with csDMARDs had an exposure of 4081 patient/years. The SI IR was 30.54 (CI 27.18-34.30) for all bDMARDs and 5.15 (CI 3.36-7.89) for csDMARDs. The aIRR between the two groups was 2.03 ([1.05, 3.9] p = 0.034) for the first 6 months of treatment but subsequently increased to 8.26 ([4.32, 15.76] p < 0.001). The SI IR for bDMARDs decreased over time in both registries, dropping from 36.59 (28.41-47.12) in 2012 to 7.27 (4.79-11.05) in 2016. Conclusion While SI remains a major concern in South American patients with RA treated with bDMARDs, a favourable trend toward a reduction was observed in the last years. Key Points • New comprehensive data on biologic drugs safety from international collaboration in South America. • First proposal for national registries data merging in South America. • Serious infections remain a major concern in RA patients treated with biologics. • A significant reduction of serious infections in RA patients exposed to biologics was observed over a 7 years period.

BackgroundAdvances in rheumatology and new therapeutic options have certainly impacted patient survival, changing the age range, from youth to seniors. The differences between the age groups could influence the evolution of the disease and the adverse events (AEs) related to the treatments. There are few real-world data on the safety and efficacy of treatments in different age groups.ObjectivesTo evaluate the frequency of AEs and the survival of treatments according to the age in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) or ankylosing spondylitis (AS).MethodsRetrospective, observational, multicenter study of real-life data of patients included in the BIOBADASAR 3.0 registry; exposed and not exposed to original biological treatments (b-DMARDs), biosimilars, targeted synthetic drugs (ts-DMARDs). The unexposed group received treatment with conventional disease-modifying drugs (cDMARDs). A Kaplan-Meier and Log Rank Test analysis was performed to study AEs-free survival and treatment in different age groups (young people <25; young adults 25-34; mature adults 34-65; old adults >65). Factors related to treatment survival were evaluated using Cox regression models.Results5,297 patients were included, 80.3% female, mean age 43.7 years (SD 15.6) and median disease progression 14.3 [IQR 11.5]. RA 4658 (87.9%); APs 490 (9.25%) and EA 149 (2.8%). The main reason for treatment discontinuation was ineffectiveness, in 624 patients in the exposed group and in 53 (2.5%) patients in control group, followed by the presence of AEs in 352 (11.2%) and 83 (3.9%), respectively (p=0.001).A mean Charlson Score of 0.268 (SD 0.6) in the exposed group and 0.306 (SD 0.7) in the control group (p=0.095). Median EAs-free survival in the exposed group was 12.5 years [IQR 16.6] while in controls was 28 years [IQR 11], p<0.0001. Median AEs-free survival was 12 years (IQR 11) in young people, 11.5 years [IQR: 4.9] in young adults, 10 years [IQR: 3.25] in mature adults and 7.6 years [IQR: 6] in old adults with a difference statistically significant (p>0.017). The exposed group presented a median treatment survival in years of 11.25 years [IQR: 10] in young people; 12.5 years [IQR: 4.7] in young adults, 7.5 years [IQR: 12.1] in mature adults and 4.5 years [IQR: 1.14] in old adults (p>0.0001). Considering only the first line of treatment, a median survival of 11.5 years [IQR: 10] was evidenced in the age group <25; 12 years [IQR: 2.6] between 25-34 years old, 10 years [IQR: 12] in the group between 34-65 years old and 5.5 years [IQR: 1.14] in the group > 65 years old (p>0.004). (Figure 1). Considering the second line of treatment, the differences between the groups were not statistically significant (p=0.57). In the multivariate regression model for patients with RA, the factors with the greatest impact on treatment survival were female sex (HR 1.3, 95% CI 1.2-1.4), old age (HR 1.01, 95% CI 1.008-1.01), treatment with steroids (HR 1.19, 95% CI1.1-1.2) and longer disease duration (HR 1.01, 95% CI1.01 – 1.02).ConclusionIn the present study we were able to demonstrate a greater occurrence of AEs in old adults and mature adults compared to young people and young adults. Conversely, survival for b-DMARDs and ts-DMARDs were greater in youth and young adults. In patients with RA, female sex, corticosteroid therapy, old aged and longer disease duration were associated with treatment discontinuation.References[1]Souto A, et al. Rate of discontinuation and drug survival of biologic therapies in rheumatoid arthritis: a systematic review and meta-analysis of drug registries and health care databases. Rheumatology (Oxford). 2016;55(3):523–34.[2]Ray D, et al. Immune senescence, epigenetics and autoimmunity. Clin Immunol. 2018 Nov;196:59-63. doi: 10.1016/j.clim.2018.04.002. Epub 2018 Apr 11.[3]Vela P, et al. Influence of age on the occurrence of adverse events in rheumatic patients at the onset of biological treatment: data from the BIOBADASER III register. Arthritis Res Ther. 2020 Jun 15;22(1):143. doi: 10.1186/s13075-020-02231-x.Disclosure of InterestsNone declared

Objectives. To assess the proportion, the reasons, and the factors associated with discontinuation or nonpublication of randomized controlled trials (RCTs) on connective tissue diseases (CTDs). Methods.We searched all interventional RCTs on CTDs registered in Clinicaltrials.gov since 2000. Two reviewers selected studies according to pre-specified eligibility criteria. Completion status, publication status, reported reasons for discontinuation or nonpublication, were retrieved on Clinicaltrials.gov, through literature search, and by contacting investigators. Multivariable logistic regression was used to identify factors associated with study noncompletion and nonpublication.Results. We included 175 studies, mostly phase 3, placebo-controlled trials on pharmacologic treatments, recruiting patients with systemic lupus (51%), systemic sclerosis (20%), Sjögren syndrome (12%) or other CTDs. Fifty-eight (33%) had been discontinued, mainly for insufficient patient accrual, with no differences in discontinuation rates across the CTDs (P>0.5). Forty-six (35%) of 130 studies having included at least 1 patient resulted unpublished, and 86 (65%) were published in a peer-reviewed journal after a median of 24 months (IQ 15-41) from completion, with a significant higher publication rate in completed vs. discontinued studies (81% vs 22%; P<0.001). We were able to obtain reasons for nonpublication in one-third of cases.Small sample size (< 100 participants) was the only factor associated with study noncompletion and nonpublication.Conclusions. One of three registered CTD-RCTs fails to be completed or published. This represents a waste of resources and raises ethical concerns regarding hidden clinical data and unfruitful participation by patients. Significance and innovation Trial discontinuation and nonpublication represent a waste of resources and raise ethical concerns regarding hidden clinical data and unfruitful participation by patients. One of three CTD-RCTs registered after 2000 failed to be completed or published, with similar rates recorded across CTDs.

Background: The analysis of the main features of randomized controlled trials (RCTs) on ANCA-associated vasculitis (AAV) can inform future study design. Methods: We searched within the International Clinical Trials Registry Platform all registered RCTs on AAV from October 2008 to December 2018. Two reviewers selected studies according to pre-specified eligibility criteria. We retrieved information including countries, funding, design, sample sizes, eligibility criteria, primary outcomes (POs), and treatments. Results: Among the 40 RCTs identified, 22 (55%) were conducted in Europe, 29 (72,5%) in a single country, 14 (35%) were industry-funded. The median number of patients planned to enrol was 68 (IQR 36-138). Only 28% of RCTs targeted a single vasculitis, and ANCA negative patients were not included in about 40% of studies. Interventions investigated were mainly drugs given to induce (40%) or maintain (32.5%) remission. Eighty-five percent of POs were considered being 'patient-important', but discrepancies in definition of disease states, such as remission or relapse were observed. Glucocorticoids use was part of the PO in < 25% of studies. The number of trials targeting a single disease, non-industry funded, incorporating glucocorticoids in PO, as well as the planned sample size increased over time. Conclusion: Despite the important achievements in the field, a better harmonization of eligibility, and outcome criteria across studies is an important objective to pursue in next future.