Efficacy of a tight-control and treat-to-target strategy in axial spondyloarthritis: results of the open-label, pragmatic, cluster-randomised TICOSPA trial.

OBJECTIVES: To compare the benefits of a tight-control/treat-to-target strategy (TC/T2T) in axial spondyloarthritis (axSpA) with those of usual care (UC). METHODS: Pragmatic, prospective, cluster-randomised, controlled, open, 1-year trial (NCT03043846). 18 centres were randomised (1:1). Patients met Axial Spondylo Arthritis International Society (ASAS) criteria for axSpA, had an Ankylosing Spondylitis Disease Activity Score (ASDAS) ≥2.1, received non-optimal treatment by non-steroidal anti-inflammatory drugs and were biologic-naive. INTERVENTIONS: (1) TC/T2T: visits every 4 weeks and prespecified strategy based on treatment intensification until achieving target (ie, ASDAS <2.1); (2) UC: visits every 12 weeks and treatment at the rheumatologist's discretion. MAIN OUTCOME: Percentage of patients with a ≥30% improvement on the ASAS-Health Index (ASAS-HI). Other efficacy outcomes and adverse events were recorded. A health economic evaluation was performed. STATISTICAL ANALYSIS: Two-level mixed models were used to estimate efficacy outcomes. Cost-effectiveness was assessed by the incremental cost per quality-adjusted life-year (QALY) gained for TC/T2T versus UC. RESULTS: 160 patients were included (80/group). Mean (SD) age was 37.9 (11.0) years and disease duration was 3.7 (6.2) years; 51.2% were men. ASDAS at inclusion was 3.0 (0.7), and ASAS-HI was 8.6 (3.7). ASAS-HI improved by ≥30% in 47.3% of the TC/T2T arm and in 36.1% of those receiving UC (non-significant). All secondary efficacy outcomes were more frequent in the TC/T2T arm, although not all statistically significant. Safety was similar in both arms. From a societal perspective, TC/T2T resulted in an additional 0.04 QALY, and saved €472 compared with UC. CONCLUSION: TC/T2T was not significantly superior to UC for the primary outcome, while many secondary efficacy outcomes favoured it, had a similar safety profile and was favourable from a societal health economic perspective. TRIAL REGISTRATION NUMBER: NCT03043846.

Progressive lung fibrosis and mortality can occur in early systemic sclerosis patients without pulmonary abnormalities at baseline assessment.

OBJECTIVES: In systemic sclerosis, baseline extent of radiological involvement is an important outcome predictor and baseline absence of radiological involvement suggests a more favourable prognosis. As current predictive models are based on cohorts with variable disease duration, we aim to assess disease dynamics in early disease. METHODS: Patients were included from the prospective longitudinal Belgian Systemic Sclerosis Cohort. We included patients with a disease duration < = 36 months at baseline with available baseline thoracic high-resolution computed tomography (HRCT) images and longitudinal pulmonary function test (PFT) results until 42 months of follow-up. RESULTS: Fifty-two patients were included; 50% were male and 44% suffered from diffuse cutaneous systemic sclerosis. A total of 46% carried anti-topoisomerase 1 antibodies. The mean disease duration at baseline visit was 11 months. At baseline visit, 40.4% (21/52) patients had HRCT abnormalities. Patients with abnormal HRCT findings more frequently suffered from diffuse cutaneous systemic sclerosis (p < 0.05) and less frequently carried anti-centromere antibodies (p < 0.05). Patients without CT abnormalities at baseline had a shorter disease duration (9 ± 7 months versus 14 ± 12 months). After 42 months, 8/52 patients, including 3 patients with normal HRCT findings at baseline, died due to SSc-related manifestations. Progression of lung fibrosis occurred in 16 patients at month 42, including 7 patients with normal CT at baseline. No clear predictors of progression could be identified. CONCLUSION: In early SSc patients, the disease dynamics differ from the large published cohorts. Progressive lung fibrosis and mortality can also occur in patients without radiological abnormalities at baseline. Key Points • Disease dynamics in early SSc differ from more established SSc. • In early SSc, progressive pulmonary fibrosis can occur in patients without CT abnormalities at baseline. • In early SSc, more stringent pulmonary follow-up is warranted both in lcSSc and dcSSc.

The role of high-resolution manometry in the assessment of upper gastrointestinal involvement in systemic sclerosis: a systematic review.

Systemic sclerosis (SSc) affects the upper gastrointestinal (GI) system in 90% of patients. High-resolution manometry (HRM) assesses esophageal dysmotility, but its role in diagnosis and follow-up remains unclear. The objectives of this systematic review were to investigate the role of HRM in the assessment of SSc-associated upper GI involvement and to evaluate the correlation between HRM abnormalities and clinical characteristics and the effects of therapeutic interventions on HRM findings. Fifteen articles were included. Most (11/15) studies were of very good or good quality. Most studies assessed correlations between esophageal symptoms and esophageal dysmotility. Two studies assessed the effectiveness of buspirone and reported HRM findings. Studies assessing upper GI symptoms using validated questionnaires, such as the University of California Scleroderma Clinical Trial Consortium Gastrointestinal Tract 2.0 or Gastrointestinal Symptoms Severity Index score, found an association between absent contractility on HRM and upper GI symptoms, but even asymptomatic patients often have esophageal body dysmotility on HRM. Esophageal dysmotility positively correlates with the presence of interstitial lung disease on high-resolution computed tomography and reduced diffusion capacity (< 0.8 of predicted value). Trials investigating the effect of buspirone demonstrate both increased lower esophageal sphincter resting pressure and reduced upper GI symptoms. Most studies report on limited patient numbers and retrospective data. Potential bias was minimized using quality appraisal. HRM findings correlate to upper GI symptoms when assessed by validated questionnaires and can detect response to therapy in buspirone trials. Esophageal body dysmotility on HRM positively correlates with the presence of interstitial lung disease. KEY POINTS: • Esophageal body dysmotility on HRM correlates with presence of ILD. • HRM findings seem to correspond to clinical symptom alleviation in interventional trials, but data are still limited. • At present HRM, a procedure with a high negative burden to the patient, offers little to no role in the therapeutic strategy.

The epidemiology of ankylosing spondylitis and the commencement of anti-TNF therapy in daily rheumatology practice.

OBJECTIVES: This study aimed to describe the epidemiology of ankylosing spondylitis (AS) in rheumatology practice at the beginning of the anti-TNF (tumour necrosis factor) era, and to evaluate the initiation of anti-TNF therapy in a clinical setting where prescription is regulated by the authority's imposed reimbursement criteria. METHODS: Between February 2004 and February 2005, all Belgian rheumatologists in academic and non-academic outpatient settings were invited to register all AS patients who visited their practice. A random sample of these patients was further examined by an in-depth clinical profile. In a follow-up investigation, we recorded whether patients initiated anti-TNF therapy and compared this to their eligibility at baseline evaluation. RESULTS: 89 rheumatologists participated and registered 2141 patients; 1023 patients were clinically evaluated. These 847 fulfilled the New York modified criteria for definite AS and 176 for probable AS. The profile of AS in rheumatology practice is characterised by longstanding and active disease with a high frequency of extra-articular manifestations and metrological and functional impairment. At a median of 2 months after the clinical evaluation, anti-TNF therapy was initiated in 263 of 603 (44%) evaluable patients with definite AS and in 22 of 138 (16%) evaluable patients with probable AS (total 38%). More than 85% of the patients who started anti-TNF therapy had an increased Bath Ankylosing Spondylitis Disease Activity Index despite previous NSAID (non-steroidal anti-inflammatory drug) use. CONCLUSIONS: Of a representative cohort of 1023 Belgian AS patients seen in daily rheumatology practice, about 40% commenced anti-TNF therapy. Decision factors to start anti-TNF therapy may include disease activity and severity.