Session Type: Abstract Submissions (ACR)
Background/Purpose: A number of clinical trials using intensive immunosuppression followed by autologous haematopoietic stem cell transplantation (HSCT) in systemic sclerosis (SSc) are underway or have been recently completed. Inclusion criteria for these trials aim to recruit cases with poor outcome, so that potential treatment-related complications, including significant early mortality are justified. Exclusion criteria are selected to minimise treatment related mortality, especially from the conditioning regimen, by defining severe organ-based disease that might preclude HSCT.
We explored morbidity and mortality in a cohort of SSc patients that fulfil the eligibility criteria for one of those trials (ASTIS) but who have been treated with standard immunosuppression.
Methods: Patients were identified from a cohort of 398 incident SSc cases with disease onset between 1995 and 1999, using ASTIS trial inclusion criteria (age 16-65 years; diffuse cutaneous (dc)SSc with disease duration ≤ 4 year plus modified Rodnan skin score (mRss) ≥ 15 plus either respiratory, renal or cardiac involvement or dcSSc with disease duration ≤ 2 years plus mRss ≥ 20 plus ESR > 25mm/1st h and/or Hb < 11g/dL) and exclusion criteria, relating to severe organ disease (respiratory, renal or cardiac) and malignancy.
Results: Of the 146 dcSSc cases, 87 fulfilled the inclusion and 66 satisfied both inclusion and exclusion criteria for the ASTIS trial. The final group was 82% female and 82% Caucasian. At the time patients fulfilled the trial eligibility criteria, mean age was 47 (range 17-65) years and disease duration was 20 months (range 1-44). Mean mRss was 30 (range 15-54), 23 (35%) of the patients carried anti-topoisomerase I antibody, 11 (17%) anti-RNA polymerase antibody and 4 (6%) anti-U3RNP antibody. Smoking status was known for 57 of the patients – 21% were current, 21% past and 58% were non-smokers.
Pulmonary fibrosis (PF), confirmed by high resolution CT was present in 55 (83%) of the patients, scleroderma renal crisis (SRC) in 2 patients (3%) and cardiac SSc in 5 patients (7.5%). Cumulative incidence of severe organ disease at 5 and 10 years of follow-up were 44% and 53% for clinically significant PF, 5% and 15% for PH, 5% and 7% for SRC and 13% for cardiac SSc.
Survival among the 66 patients was 95% at 2, 89% at 5 and 72% at 10 years. Survival among patients with present or past smoke exposure was marginally worse (87% at 5 and 74% at 10 years) compared to non-smokers (97% at 5 and 81% at 10 years), but difference was not significant. We also analysed all 87 patients who fulfilled the inclusion criteria only, not excluding those with severe organ disease or malignancy and survival among those was marginally worse (86% at 5 years and 68% at 10 years) confirming that the more severe cases that would be excluded from HSCT protocols do indeed have a worse outcome.
Conclusion: Our findings demonstrate that survival of cases that would have been eligible for ASTIS trial is substantially better than might have been predicted historically, especially when excluding patients with severe organ disease that are not suitable for HSCT. This must be taken into account when long-term outcomes for trials such as ASTIS are considered.
S. I. Nihtyanova,
V. H. Ong,
C. P. Denton,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/outcomes-linked-to-intensive-treatment-trials-in-systemic-sclerosis/