The mortality rate among people with systemic sclerosis (SSc) has not changed over time and continues to be high, according to a combined analysis of a French multicenter cohort study and a literature review. Apart from already reported prognostic factors, the researchers also found new potential predictors of SSc outcome.
The study “Survival and prognosis factors in systemic sclerosis: data of a French multicenter cohort, systematic review, and meta-analysis of the literature” was published in the journal Arthritis Research & Therapy.
Heart and respiratory complications are the leading causes of death among people SSc. However, studies on SSc mortality rates are contradictory, and more often describe prevalent cases — all SSc cases, regardless of the time of diagnosis — rather than incident cases (new SSc diagnoses).
In addition, while some systematic literature review analyses, called meta-analyses, have assessed mortality and prognostic factors, they did not take into consideration the patients’ genetic background and self-targeting antibody profiles.
The researchers in this study used two approaches to investigate prognosis and survival factors associated with SSc. They first assessed a multicenter French cohort of incident SSc patients, and then performed a meta-analysis and systematic review on SSc prognostic factors, and survival or mortality rates.
Standardized mortality ratio, comparing the deaths observed in the study group with the deaths of the general population, served to assess mortality. Here, a number higher than 1.0 indicates higher mortality in the SSc study group.
The team performed its group analysis by assess 625 SSc patients (mean age at disease onset of 52.7 years) enrolled from the French National Scleroderma Cohort. The median disease duration from onset to start of the study was 0.8 years, and the median follow-up time was 4.4 years.
Comparison with the general population showed a standardized mortality ratio of 5.73 in the cohort study.
Analysis of patient survival rates after 1, 3, 5, 10, and 15 years showed survival rates of 98.0%, 92.5%, 85.9%, 71.7%, and 53%, respectively. According to the data, patients with limited cutaneous SSc had a significantly better survival rate, compared with those with diffuse cutaneous SSc.
When researchers assessed potential prognostic factors, they confirmed several features already associated with poor prognosis in SSc in previous reports. These factors included older age (above 60), diffuse cutaneous SSc, impaired lung and cardiac functions, pulmonary hypertension and interstitial lung disease involvement, kidney problems, and inflammation.
Interestingly, several new prognostic factors were found. A poor prognosis was associated with telangiectasia (small dilated blood vessels near the skin surface), shorter distances on the six-minute walk test (6MWD; a test assessing exercise capacity), defects related to the heart valves, and cancer.
The team then reviewed 44 studies related to mortality (18 articles representing 11,719 patients), and prognosis factors (36 articles representing 26,187 patients).
The pooled standardized mortality ratio for all studies was 3.45. Among these, incident cases had a mortality ratio of 3.64 and prevalent cases a ratio of 3.28. The statistical comparison showed no significant difference between the two types of cases.
Similar to the cohort study, the meta-analysis showed a higher mortality ratio associated with diffuse cutaneous SSc. Higher mortality also correlated with the occurrence of anti-Scl70 antibodies — antibodies mainly present in diffuse cutaneous and more severe SSc.
Finally, the literature analysis of prognostic factors showed that a poor prognosis was associated with male sex and African origin, apart from the factors already found in the cohort study, or the occurrence of anti-Scl70 antibodies. In contrast, the presence of antibodies targeting centromeres (specialized DNA sequences in chromosomes that link a pair of sister chromatids) correlated with better survival.
“Our results show that mortality is still high in SSc,” the researchers said, adding that the study “confirms previously described prognosis factors related to skin extension and organ involvement while identifying additional prognosis factors such as autoantibody status, telangiectasia, 6MWD, and valvular disease.”
The team emphasized that the study “did not show any improvement of SMR [standardized mortality ratio] over time.”