Long-term safety of certolizumab pegol in rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis, psoriasis and Crohn's disease: a pooled analysis of 11 317 patients across clinical trials.

Objective: To review long-term certolizumab pegol (CZP) safety across all approved indications: rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), psoriasis (PSO) and Crohn's disease (CD). Methods: Data were pooled across 49 UCB-sponsored CZP clinical trials (27 RA, one axSpA, one PsA, five PSO, 15 CD) to August 2017. Serious adverse events (SAEs) of interest (infections, malignancies, autoimmunity/hypersensitivity events, major adverse cardiovascular events (MACE), gastrointestinal (GI) perforations, psoriasis events, laboratory abnormalities) and deaths were medically reviewed by an external expert committee, using predefined case rules. Incidence rates (IRs)/100 patient-years (PY) are presented by indication; standardised mortality and malignancy rates were calculated using WHO/GLOBOCAN/SEER databases. Pregnancies with maternal CZP exposure are also reported. Results: Of 11 317 CZP-treated patients across indications (21 695 PY CZP exposure; maximum: 7.8 years), infections were the most common SAEs (overall IR: 3.62/100 PY; IRs ranged from 1.50/100 PY(PSO) to 5.97/100 PY(CD)). The IR for malignancies was 0.82/100 PY, including lymphoma (0.06/100 PY). MACE and GI perforation IRs in CZP-treated patients were 0.47/100 PY and 0.08/100 PY and were highest in RA and CD, respectively. Patients with PSO had the lowest SAE rates. The incidence of deaths and malignancies aligned with expected general population data. Conclusion: This extensive overview of the CZP safety profile in clinical trials, across all indications, provides large-scale confirmation of previous reports. No new safety signals or relevant non-disease-related laboratory abnormalities were identified. The study demonstrated some indication-specific differences in certain SAE rates that may be attributable to the underlying inflammatory disease.

Incidence and Prevalence of Major Adverse Cardiovascular Events in Rheumatoid Arthritis, Psoriatic Arthritis, and Axial Spondyloarthritis.

OBJECTIVE: To compare the risk of major adverse cardiovascular events (MACE) in a large observational cohort of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), or axial spondyloarthritis (SpA) patients. METHODS: We conducted a mixed retrospective and prospective cohort study using data from patients with RA, PsA, or axial SpA included in the Swiss Clinical Quality Management registry. The primary outcome of interest was a composite of myocardial infarction, transient or permanent cerebrovascular event, or cardiovascular-associated death. RESULTS: A total of 5,315 patients were eligible for the analysis of incidence, with a total follow-up time of 37,495 patient-years for RA, 19,837 patient-years for axial SpA, and 9,171 patient-years for PsA. The unadjusted incidence rate of MACE per 1,000 patient-years was 2.67 for RA, 1.41 for axial SpA, and 1.42 for PsA. Compared to the unadjusted incidence rate ratios (IRRs) in patients with RA, those in patients with axial SpA were 0.53 (95% confidence interval [95% CI] 0.34-0.80; P = 0.003) and in patients with PsA were 0.53 (95% CI 0.30-0.95; P = 0.03). After adjustment for traditional cardiovascular risk factors, age at disease onset, sex, and disease duration, the difference was not significant between RA and axial SpA (adjusted IRR 0.93 [95% CI 0.51-1.69]; P = 0.80) or between RA and PsA (adjusted IRR 0.56 [95% CI 0.27-1.14]; P = 0.11). We found a similar result with the analysis of prevalence. CONCLUSION: There was no significant difference in the incidence and prevalence of MACE between RA and axial SpA or PsA, suggesting that inflammation, rather than a particular disease, drives the increased risk of cardiovascular disease.

Efficacy and drug survival of anti-tumour necrosis factor-alpha therapies in patients with non-radiographic axial spondyloarthritis: an observational cohort study from Southern Sweden.

OBJECTIVES: To evaluate the efficacy and drug survival of anti-tumour necrosis factor (anti-TNF) therapy in non-radiographic axial spondyloarthritis (nr-axSpA) patients treated in clinical practice in Southern Sweden. METHOD: In this cohort study we prospectively included 112 patients with nr-axSpA and high disease activity as well as inadequate response or intolerance to non-steroidal anti-inflammatory drugs (NSAIDs) receiving their first course of anti-TNF therapy. Patients fulfilling modified New York criteria for ankylosing spondylitis (AS) were excluded. The Assessment of SpondyloArthritis International Society (ASAS) criteria for axial SpA were fulfilled by 77% (n = 86) of the included patients. RESULTS: At baseline, the median age of the cohort was 38 years, 59% were males, 79% of the patients had imaging suggestive of sacroiliitis (primarily inflammation on magnetic resonance imaging, MRI), 71% were HLA-B27 positive, and the median disease duration was 6 years and 10 months. At 6 months of follow-up, the median Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) decreased from 5.6 to 3.2 (p = 0.002), the Bath Ankylosing Spondylitis Functional Index (BASFI) decreased from 3.9 to 1.8 (p = 0.005), and C-reactive protein (CRP) level decreased from 4.4 to 1.7 mg/L (p = 0.001). After 1 year of treatment the Kaplan-Meier estimated drug survival was 76%, and at 2 years of follow-up this value decreased to 65%. Patients with inflammatory MRI findings at baseline had significantly better drug survival [hazard ratio (HR) 0.24, 95% confidence interval (CI) 0.10-0.55, p = 0.001]. Male sex was also associated with higher drug survival (HR 0.45, 95% CI 0.24-0.85, p = 0.011). CRP level at baseline was not associated with drug survival. CONCLUSIONS: Anti-TNF treatment of patients with nr-axSpA in clinical practice resulted in reduced BASDAI and BASFI scores and good drug survival. The results from this study suggest that male gender and positive imaging at baseline are associated with a favourable treatment course.

[Development of morbidity and mortality in patients with spondyloarthritis]. / Entwicklung von Morbidität und Mortalität bei Spondyloarthritiden.

This review presents data on morbidity and mortality in patients with spondyloarthritis (SpA). Morbidity in patients with SpA is mainly determined by impairment of function and development of structural lesions. The course of illness in patients with ankylosing spondylitis (AS) is influenced by comorbidities, such as cardiovascular disease and fractures of the spine and in patients with psoriatic arthritis by peripheral joint manifestations. The mortality of patients with SpA has probably not increased but exact data are lacking. Approximately one third of AS patients will develop a severe disease state in which the mortality rate is increased by 50%.

[Rheumatoid arthritis at the cervical spine -- an underestimated problem]. / Die rheumatoide Arthritis an der Halswirbelsäule: ein unterschätztes Problem.

BACKGROUND AND OBJECTIVE: The involvement of the cervical spine in rheumatoid arthritis can be essential regarding prognosis and mortality. The cervical myelopathy due to pannus formation and/or subluxation can be fatal. Aim of this study was to demonstrate the possible changes seen by MRI, and to establish a risk-profile for the individual patient. PATIENTS AND METHOD: Within a period of 24 months 214 patients with active RA were included. Clinical and laboratory data were obtained and plain radiographs of the cervical spine were taken. In patients with pathological findings on X-ray an MRI was performed (36 patients). RESULTS: Within the group of 214 patients 36 were identified to get an cervical spine MRI. In all cases the MRI showed significant changes: in 7 (19.5 %) pannus surrounded the dens, with additional erosions in one patient (2.7 %). In 25 (69.5 %) atlanto-axial-subluxation was present, 7 (19.5 %) showed a spondylodiscitis below C2. In 10 (27.8 %) a cervical myelopathy due to pannus or subluxation was present. There was no correlation of the MRI-results with symptoms and findings by examination. The patients with cervical spine disease were in all stages of RA. The majority was rheumatoid-factor positive. 5 out of 10 patients with cervical myelopathy showed neurological deficits: 3 patients died in consequence of neural compression, 2 patients underwent surgery successfully. CONCLUSION: The early detection of a cervical spine involvement in RA is essential to avoid possibly fatal complications. The only reliable method to achieve this goal has to include radiographic diagnostic including MRI of the cervical spine. Only this approach can answer the question of the right time-point for surgery. In daily clinical practice the cervical-spine involvement in RA is still underestimated.