Mortality in Patients With Systemic Sclerosis Over 40 Years
Mortality in Patients With Systemic Sclerosis Over 40 Years
Objective. SSc is known as the most severe connective tissue disorder, and to be associated with a high mortality risk. Some improvements in therapy for SSc have been achieved in recent years and some preliminary data have suggested an improvement in patient survival. Thus, we set out to determine whether mortality rate in SSc patients has decreased over the past 40 years through a meta-analysis of cohort studies.
Methods. We performed a systematic review and a meta-analysis of literature in MEDLINE and Embase databases from January 1960 to June 2010. All cohort studies reporting on SSc mortality were analysed. We then calculated pooled standardized mortality ratios (SMRs) of SSc mortality and calculated their changes over time using meta-regression analysis.
Results. Nine studies were included, corresponding to a total of 2691 SSc patients. The pooled SMR was 3.53 [95% CI 3.03, 4.11, P<0.0001; I = 3%, P(het) = 0.001]. Mid-cohort year ranged from 1977 to 1995 (before 1980: two studies; 1980–90: five studies; and after 1990: two studies): adjusted meta-regression analysis did not show significant change in SMR over time (P = 0.523). Among 732 deaths, heart involvement was the most frequent cause of deaths (29%) followed by lung involvement.
Conclusion. Our results confirm that SSc is a devastating condition as reflected by a pooled SMR of 3.5. Additionally, SMR has not significantly changed over the past 40 years. Further studies are needed to assess the effect of the most recent available therapies on mortality in SSc.
Among the many different immune-mediated rheumatic diseases, SSc stands out as a severely incapacitating and life-threatening disease. Its pathogenesis is complex and remains incompletely known. Several poor prognosis factors were identified: diffuse cutaneous subtype, presence of main organ (lung, heart and kidney) involvement, anti-Scl70 antibody, increased ESR and anaemia. The most recent studies have suggested that SSc-related deaths are mainly caused by lung involvement (pulmonary fibrosis and pulmonary hypertension) and primary heart involvement, whereas non-SSc causes include infections, malignancies and atherosclerosis.
Therapeutics options in SSc were previously supportive of organ involvement; some drugs emerged recently as preventive of organ failure, i.e. angiotensin-converting enzyme (ACE) inhibitors and calcium channel blockers. In addition, the management of SSc patients, including the accurate detection of SSc-associated organ involvement, has improved as a result of various national/international organization guidelines. Nevertheless, their impact on mortality remains unclear.
Investigations on mortality have reported an increase in SSc mortality rates since 1980, which was hypothesized by the authors as reflecting an increasing incidence of SSc. Conversely, other observational studies, referring to historical cohorts, have suggested an improvement in the overall survival over time with reduced mortality and higher survival rates in the contemporary cohorts as compared with the older ones. Improved survival in SSc, if confirmed, may be the reflection of improved survival in the general population, the consequence of preventive and therapeutics advances in the management of SSc, or both. Knowing whether SSc survival has improved less than, equal to or more than that in the general population during past decades is crucial clinical information, as yet not known. The standardized mortality ratio (SMR), which is the ratio between the observed number of deaths in a cohort to the expected number of deaths of a comparable age- and sex-matched population, is an accurate tool to assess mortality rate and its changes over time. Consequently, using this tool, we conducted a systematic review and meta-analysis of cohort studies to investigate whether mortality rate in SSc patients has changed over the past 40 years.
Abstract and Introduction
Abstract
Objective. SSc is known as the most severe connective tissue disorder, and to be associated with a high mortality risk. Some improvements in therapy for SSc have been achieved in recent years and some preliminary data have suggested an improvement in patient survival. Thus, we set out to determine whether mortality rate in SSc patients has decreased over the past 40 years through a meta-analysis of cohort studies.
Methods. We performed a systematic review and a meta-analysis of literature in MEDLINE and Embase databases from January 1960 to June 2010. All cohort studies reporting on SSc mortality were analysed. We then calculated pooled standardized mortality ratios (SMRs) of SSc mortality and calculated their changes over time using meta-regression analysis.
Results. Nine studies were included, corresponding to a total of 2691 SSc patients. The pooled SMR was 3.53 [95% CI 3.03, 4.11, P<0.0001; I = 3%, P(het) = 0.001]. Mid-cohort year ranged from 1977 to 1995 (before 1980: two studies; 1980–90: five studies; and after 1990: two studies): adjusted meta-regression analysis did not show significant change in SMR over time (P = 0.523). Among 732 deaths, heart involvement was the most frequent cause of deaths (29%) followed by lung involvement.
Conclusion. Our results confirm that SSc is a devastating condition as reflected by a pooled SMR of 3.5. Additionally, SMR has not significantly changed over the past 40 years. Further studies are needed to assess the effect of the most recent available therapies on mortality in SSc.
Introduction
Among the many different immune-mediated rheumatic diseases, SSc stands out as a severely incapacitating and life-threatening disease. Its pathogenesis is complex and remains incompletely known. Several poor prognosis factors were identified: diffuse cutaneous subtype, presence of main organ (lung, heart and kidney) involvement, anti-Scl70 antibody, increased ESR and anaemia. The most recent studies have suggested that SSc-related deaths are mainly caused by lung involvement (pulmonary fibrosis and pulmonary hypertension) and primary heart involvement, whereas non-SSc causes include infections, malignancies and atherosclerosis.
Therapeutics options in SSc were previously supportive of organ involvement; some drugs emerged recently as preventive of organ failure, i.e. angiotensin-converting enzyme (ACE) inhibitors and calcium channel blockers. In addition, the management of SSc patients, including the accurate detection of SSc-associated organ involvement, has improved as a result of various national/international organization guidelines. Nevertheless, their impact on mortality remains unclear.
Investigations on mortality have reported an increase in SSc mortality rates since 1980, which was hypothesized by the authors as reflecting an increasing incidence of SSc. Conversely, other observational studies, referring to historical cohorts, have suggested an improvement in the overall survival over time with reduced mortality and higher survival rates in the contemporary cohorts as compared with the older ones. Improved survival in SSc, if confirmed, may be the reflection of improved survival in the general population, the consequence of preventive and therapeutics advances in the management of SSc, or both. Knowing whether SSc survival has improved less than, equal to or more than that in the general population during past decades is crucial clinical information, as yet not known. The standardized mortality ratio (SMR), which is the ratio between the observed number of deaths in a cohort to the expected number of deaths of a comparable age- and sex-matched population, is an accurate tool to assess mortality rate and its changes over time. Consequently, using this tool, we conducted a systematic review and meta-analysis of cohort studies to investigate whether mortality rate in SSc patients has changed over the past 40 years.
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