Why do patients with myositis die? A retrospective analysis of a single-centre cohort.

OBJECTIVES: Causes of death in inflammatory myopathies have rarely been studied. We have assessed a cohort of myositis patients followed in a single centre over a 37-year period, reviewing the mortality rate, causes of death and predictors of poor prognosis. METHODS: We performed a single-centre, retrospective study on patients aged ≥16 years fulfilling 3 or 4 of the Bohan and Peter criteria, noting their demographic data, clinical features, serology, treatment and outcome. RESULTS: Of 97 patients identified, 74.2% were female. The mean age at diagnosis was 40.5 years (SD 13.2). 38.1% had adult-onset dermatomyositis, 36.1% adult-onset polymyositis and 25.8% overlap myositis. 96.9% had upper and lower limb involvement (UL+/LL+) and 62.9% had a highest CK≥10 times the upper limit of normal. 33% had significant infection(s). The disease course was chronic persistent in 29.9%, relapsing and remitting in 34% and monophasic in 36.1%. All received steroids and 92.8% other immunosuppressant(s). The median follow-up was 9 years (IQR 11.5). The estimated cumulative proportion survival at 5, 10, 15 and 20 years were 94.6%, 82.2%, 72,1% and 66.1%, respectively. 24.7% of patients died, mostly due to infection (29.2%). In univariate analysis, lung involvement (HR 1.78, p=0.013), infection (HR 4.18, p=0.003) and UL+/LL+ (HR 0.13, p=0.010) were statistically significantly associated with the risk of death. In the multivariate analysis infection (HR 3.68, p=0.009) and UL+/LL+ (HR 0.16, p=0.027) were statistically significantly associated with survival. CONCLUSIONS: A good long-term survival is reported. Nevertheless, careful follow-up of myositis patients is important.

Profile of atacicept and its potential in the treatment of systemic lupus erythematosus.

The importance of B cell activating factors in the generation of autoantibodies in patients with systemic lupus erythematosus (SLE) is now recognized. The two key factors, known as BAFF and APRIL, produced by a variety of cells including monocytes, dendritic cells and T cells, also help to regulate B cell maturation, function and survival. Biologic agents that block these factors have now been developed and tried out in large scale clinical trials in SLE patients. Benlysta which blocks BAFF has met some of its end points in clinical trials and is approved for use in patients with skin and joint disease who have failed conventional drugs. In contrast, clinical trials using atacicept which blocks both BAFF and APRIL have been more challenging to interpret. An early study in lupus nephritis was, mistakenly, abandoned due to serious infections thought to be linked to the biologic when in fact the dramatic fall in the immunoglobulin levels took place when the patients were given mycophenolate, prior to the introduction of the atacicept. Likewise the higher dose arm (150 mgm) of a flare prevention study was terminated prematurely when 2 deaths occurred. However, the mortality rate in this study was identical to that seen in the Benlysta studies and a post hoc analysis found a highly significant benefit for the 150mgm arm compared to the lower dose (75 mgm) and placebo arms. Other trials with both Benlysta and atacicept are on-going.