Aaron Juche

Gastroesophageal reflux disease (GERD) occurs frequently in patients with SSc. We investigated whether the presence of GERD and/or the use of anti-acid therapy, specifically proton-pump inhibitors (PPIs), are associated with long-term outcomes, especially in SSc-associated interstitial lung disease (SSc-ILD). We retrospectively analysed patients with SSc and SSc-ILD from the German Network for Systemic Sclerosis (DNSS) database (2003 onwards). Kaplan–Meier analysis compared overall survival (OS) and progression-free survival (PFS) in patients with GERD vs without GERD (SSc and SSc-ILD), and PPI vs no PPI use (SSc-ILD only). Progression was defined as a decrease in either percentage predicted forced vital capacity of ≥10% or single-breath diffusing capacity for carbon monoxide of ≥15%, or death. It was found that 2693/4306 (63%) registered patients with SSc and 1204/1931 (62%) with SSc-ILD had GERD. GERD was not associated with decreased OS or decreased PFS in patients in either cohort. In SSc-ILD, PPI use was associated with improved OS vs no PPI use after 1 year [98.4% (95% CI: 97.6, 99.3); n = 760 vs 90.8% (87.9–93.8); n = 290] and after 5 years [91.4% (89.2–93.8); n = 357 vs 70.9% (65.2–77.1); n = 106; P < 0.0001]. PPI use was also associated with improved PFS vs no PPI use after 1 year [95.9% (94.6–97.3); n = 745 vs 86.4% (82.9–90.1); n = 278] and after 5 years [66.8% (63.0–70.8); n = 286 vs 45.9% (39.6–53.2); n = 69; P < 0.0001]. GERD had no effect on survival in SSc or SSc-ILD. PPIs improved survival in patients with SSc-ILD. Controlled, prospective trials are needed to confirm this finding.

Background The interest in pharmaceutical trials in giant cell arteritis (GCA) is increasing. Trial recruitment may be more challenging in GCA than in other rheumatic diseases because of a higher proportion of elderly patients who are additionally faced with a new diagnosis when being considered for trial participation. Objectives To analyse the eligibility of newly diagnosed and flaring GCA patients in one centre for randomization in the SIRRESTA trial (ClinicalTrials.gov Identifier, NCT02531633; sirukumab versus placebo), to list reasons for non-randomization, and to compare eligible with non-eligible patients. Methods All patients with newly diagnosed or relapsing GCA considered for trial participation between August 2016 until trial termination in October 2017 were included. The trial was prematurely terminated by the sponsor based on the decision to discontinue development of sirukumab in autoimmune diseases. Analysis of variance, two-sided Fisher’s exact and Pearson’s chi-squared tests were applied for calculating statistical significance. Comparison of eligible and non-eligible GCA patients for trial participation Results Ninety-five patients were pre-screened. Fifteen of these patients were screened and only 12 of the 95 (13%) pre-screened GCA patients were eligible for randomization based on inclusion and exclusion criteria. The other 83 patients were not eligible for one or more of the following reasons: Concomitant diseases (42%) including second autoimmune disease (11%), malignancy (6%), history of diverticulitis (5%), hepatopathy (2%), renal insufficiency (1%) frailty (6%) and dementia (2%), ischaemic disease (2%; 1 myocardial infarction and 1 severe tongue necrosis), abnormal or inconclusive tests for tuberculosis (5%) and hepatitis (1%); failure to meet inclusion criteria (41%), including symptoms (12%), histology/imaging (1%), exceedance of maximum glucocorticoid dose (7%), too low ESR and CRP (10%), too long treatment duration (11%); declined consent (29%), before (11%) and after receiving the consent form (18%); too long distance to study centre (5%). Patients eligible for the trial were younger. They had no ischaemic complications (see table 1). A higher proportion of relapsing GCA patients were included. This subgroup of a larger trial represents only data from one centre. It may not be representative for the findings in other centres or the whole study. Conclusions Many newly diagnosed or relapsing GCA patients were not eligible for a trial due to concomitant diseases, failing inclusion criteria or declined consent. Eligible patients were younger; and more had relapsing disease. Disclosure of Interest W. Schmidt Grant/research support from: Roche, GSK (principle investigator), Consultant for: Roche, GSK, Sanofi, Speakers bureau: Roche, K. Hofheinz: None declared, S. Burger Grant/research support from: GSK (sub-investigator), V. Schäfer Grant/research support from: GSK (sub-investigator), A. Juche Grant/research support from: GSK (sub-investigator)