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Annals of the rheumatic diseases [journal]
- A gender gap in primary and secondary heart dysfunctions in systemic sclerosis: a EUSTAR prospective study. [JOURNAL ARTICLE]
- Ann Rheum Dis 2014 Oct 23.
In agreement with other autoimmune diseases, systemic sclerosis (SSc) is associated with a strong sex bias. However, unlike lupus, the effects of sex on disease phenotype and prognosis are poorly known. Therefore, we aimed to determine sex effects on outcomes.We performed a prospective observational study using the latest 2013 data extract from the EULAR scleroderma trials and research (EUSTAR) cohort. We looked at (i) sex influence on disease characteristics at baseline and (ii) then focused on patients with at least 2 years of follow-up to estimate the effects of sex on disease progression and survival.9182 patients with SSc were available (1321 men) for the baseline analyses. In multivariate analysis, male sex was independently associated with a higher risk of diffuse cutaneous subtype (OR: 1.68, (1.45 to 1.94); p<0.001), a higher frequency of digital ulcers (OR: 1.28 (1.11 to 1.47); p<0.001) and pulmonary hypertension (OR: 3.01 (1.47 to 6.20); p<0.003). In the longitudinal analysis (n=4499), after a mean follow-up of 4.9 (±2.7) years, male sex was predictive of new onset of pulmonary hypertension (HR: 2.66 (1.32 to 5.36); p=0.006) and heart failure (HR: 2.22 (1.06 to 4.63); p=0.035). 908 deaths were recorded, male sex predicted deaths of all origins (HR: 1.48 (1.19 to 1.84); p<0.001), but did not significantly account for SSc-related deaths.Although more common in women, SSc appears as strikingly more severe in men. Our results obtained through the largest worldwide database demonstrate a higher risk of severe cardiovascular involvement in men. These results raise the point of including sex in the management and the decision-making process.
- The antibody response against human and chimeric anti-TNF therapeutic antibodies primarily targets the TNF binding region. [JOURNAL ARTICLE]
- Ann Rheum Dis 2014 Oct 23.
In a subset of patients, anti tumour necrosis factor (TNF) therapeutic antibodies are immunogenic, resulting in the formation of antidrug antibodies (ADAs). Neutralising ADAs compete with TNF for its binding site and reduces the effective serum concentration, causing clinical non-response. It is however unknown to which extent ADAs are neutralising.To study which proportion of antibodies to human(ised) anti-TNF (adalimumab, golimumab, certolizumab) as well as chimeric anti-TNF (infliximab) is neutralising.Neutralising capacity of ADAs was assessed using a TNF competition assay in ADA-positive sera of patients treated with adalimumab (n=21), golimumab (n=4), certolizumab (n=9) or infliximab (n=34) sent in to our diagnostic department.In 34 sera with ADAs to adalimumab, golimumab or certolizumab, >97% of the antibodies were neutralising. In 34 sera with ADAs to infliximab >90% of the antibodies were neutralising. Further characterisation of the broader antibody response to infliximab revealed that non-neutralising antibodies to infliximab do not target murine domains, but may bind infliximab-unique domains not involved in TNF binding (located outside the paratope).Our study shows that ADAs to human(ised) as well as chimeric anti-TNF therapeutic antibodies are largely neutralising. This highly restricted ADA response suggests an immunodominant role for the paratope of anti-TNF therapeutics.
- Risk of vascular disease with gout: overadjustment of the statistical analyses? [LETTER]
- Ann Rheum Dis 2014 Oct 21.
- Bone density in osteoarthrosis. [Journal Article]
- Ann Rheum Dis 1975 Dec.:Suppl 130-1.
- Contribution to the study of the initial stage of cartilage degeneration. [Journal Article]
- Ann Rheum Dis 1975 Dec.:Suppl 125-9.
- Articular cartilage lesions in the Liverpool population. [Journal Article]
- Ann Rheum Dis 1975 Dec.:Suppl 122-4.
- Pathogenesis of osteoarthrosis. An hypothesis. [Journal Article]
- Ann Rheum Dis 1975 Dec.:Suppl 120-1.
- Contact pressures in the loaded cadaver human hip. [Journal Article]
- Ann Rheum Dis 1975 Dec.:Suppl 114.
- Mechanical properties of articular cartilage and their relationship to matrix degradation and age. [Journal Article]
- Ann Rheum Dis 1975 Dec.:Suppl 111-3.