Mortality and survival in systemic sclerosis: Systematic review and meta-analysis

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Abstract

Objective

To determine the mortality, survival, and causes of death in patients with systemic sclerosis (SSc) through a meta-analysis of the observational studies published up to 2013.

Methods

We performed a systematic review and meta-analysis of the observational studies in patients with SSc and mortality data from entire cohorts published in MEDLINE and SCOPUS up to July 2013.

Results

A total of 17 studies were included in the mortality meta-analysis from 1964 to 2005 (mid-cohort years), with data from 9239 patients. The overall SMR was 2.72 (95% CI: 1.93–3.83). A total of 43 studies have been included in the survival meta-analysis, reporting data from 13,529 patients. Cumulative survival from onset (first Raynaud׳s symptom) has been estimated at 87.6% at 5 years and 74.2% at 10 years, from onset (non-Raynaud׳s first symptom) 84.1% at 5 years and 75.5% at 10 years, and from diagnosis 74.9% at 5 years and 62.5% at 10 years. Pulmonary involvement represented the main cause of death.

Conclusions

SSc presents a larger mortality than general population (SMR = 2.72). Cumulative survival from diagnosis has been estimated at 74.9% at 5 years and 62.5% at 10 years. Pulmonary involvement represented the main cause of death.

Introduction

Systemic sclerosis (SSc) represents one of the autoimmune systemic diseases with worse prognosis. Several studies have been performed from the 1960s of the last century reflecting a higher mortality rate between 1.05-fold and 7.2-fold [1], [2] compared with the general population. There have been changes in the pattern of death in the last decades after the introduction of new therapies, with an important reduction in the number of deaths related to kidney involvement, and, nowadays, pulmonary involvement (interstitial lung disease or pulmonary hypertension) being the leading causes of death in the majority of patients [3].

The most valuable parameter in order to compare mortality studies is the assessment of the standardized mortality ratio (SMR), a fundamental tool in the only 4 mortality meta-analyses reported in SSc [4]. The SMR is the ratio between observed mortality and expected mortality in sex- and age-matched general population. These 4 meta-analyses are based on the assessment of the SMR: Elhai et al. [5] [9 studies, overall SMR = 3.53 (3.03–4.11)], Ioannidis et al. [2] (7 studies), Toledano et al. [6] [7 studies, overall SMR = 3.51 (2.74–4.50)], and Komócsi et al. [7] (10 studies, overall SMR = 3.24). One of the goals of our systematic review and meta-analysis is to perform an actual assessment of mortality in SSc, pointing out the changes of the ratio in the last decades and the changes in the patterns of death.

Prior to the assessment of survival of any cohort, we must pay attention to the methodology of the study, because of a huge variability among them, sometimes assessing survival from diagnosis and sometimes from the onset of disease. This last data is obviously a more imprecise data but certainly more real. Several survival and mortality studies from single cohorts [1], [3], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45], [46], [47], [48], [49], [50], [51], [52], [53], [54], [55], [56], [57], [58], [59], [60], [61], [62], [63], [64], [65], [66], [67], [68], [69], [70], [71], [72], [73], [74], [75], [76], [77], [78], [79] and reviews have been published from the last mid-century, reporting data about cumulative survival at different times of follow-up and measured sometimes from the onset of disease and sometimes from the time of diagnosis. This is crucial at the time of meta-analyzing these data and to avoid any bias of selection. Risk factors for poor outcome are often reported in these studies, sometimes from univariate and sometimes from multivariate analysis. In order to assess overall survival and risk factors for poor outcome, we have performed a systematic review and posterior qualitative and quantitative meta-analysis from published articles. We have also compared survival from studies before and after 1990.

Section snippets

Methods

The studies collected in this issue are studies from patients fulfilling the ACR criteria for SSc after 1980 and the LeRoy criteria after 1988 [80], [81], except several studies before 1980. At that time, there were no standardized criteria, and diagnosis was made according to the presence of Raynaud׳s phenomenon and skin characteristic changes according to the classification by O′Leary and Waissman [82] in 1943 and by Tuffanelli and Winkelmann [83] in 1962.

The search was performed through

Mortality meta-analysis

Eventually, 17 studies were included in the meta-analysis (Table 1). These are 16 cohort studies and 1 transversal observational study from mortality records. No study was excluded because of the quality assessment. These 17 studies report data from 9239 patients. There were 7150 women (80.2%), with a mean age at onset of 44.5 years (SD = 2.9) and 48 years at enrollment (SD = 3.5). Limited subset (lcSSc) was diagnosed in 3277 patients (63.2%) and diffuse (dcSSc) in 1459 patients (28.1%). The

Conclusions

The present study constitutes the largest meta-analysis ever done in SSc for the assessment of mortality (data from 17 studies for the SMR meta-analysis and 40 for the meta-analysis of causes of death) and survival (data from 43 studies). To date, only 4 meta-analyses in the medical literature had focused on SSc mortality from the assessment of SMR [5], [2], [6], [7], reporting data from 9, 7, 7, and 10 studies, respectively. We have also focused on SMR for the assessment of mortality since it

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