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Patient acceptable symptom state in scleroderma: results from the tocilizumab compared with placebo trial in active diffuse cutaneous systemic sclerosis.

ABSTRACT: Objectives:Patient acceptable symptom state (PASS) as an absolute state of well-being has shown promise as an outcome measure in many rheumatologic conditions. We aimed to assess whether PASS may be effective in active diffuse cutaneous SSc differentiating active from placebo. Methods:Data from the phase 2 Safety and Efficacy of Subcutaneous Tocilizumab in Adults with Systemic Sclerosis (faSScinate) trial were used, which compared tocilizumab (TCZ) vs placebo over 48 weeks followed by an open-label TCZ period to 96 weeks. Three different types of PASS questions were evaluated at weeks 8, 24, 48 and 96, including if a current state would be acceptable over time as a yes vs no response and Likert scales about how acceptable a current state is if remaining over time. Additional outcomes assessed included modified Rodnan skin score, HAQ disability index (HAQ-DI), physician and patient global assessments on a visual analogue scale, CRP and ESR. Results:The placebo group consisted of 44 patients and the TCZ group had 43 patients. At baseline, 33% achieved a PASS for all three PASS questions, with the proportion increasing to 69, 71 and 78%, respectively, at 96 weeks. Changes in PASS scores showed a moderately negative correlation with HAQ-DI and patient and physician global assessments visual analogue scales, which indicates expected improvements as PASS improved. The PASS question, 'Considering all of the ways your scleroderma has affected you, how acceptable would you rate your level of symptoms?' showed significant correlations with patient-reported outcomes and differentiating placebo vs TCZ at 48 weeks (P = 0.023). Conclusion:PASS may be used as a patient-centred outcome in SSc, especially as a 7-point Likert scale. Further validation is required to determine the utility as an outcome measure in trials and clinical practice.

SUBMITTER: Arnold MB

PROVIDER: S-EPMC5850780 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Patient acceptable symptom state in scleroderma: results from the tocilizumab compared with placebo trial in active diffuse cutaneous systemic sclerosis.

Arnold Michael B MB Khanna Dinesh D Denton Christopher P CP van Laar Jacob M JM Frech Tracy M TM Anderson Marina E ME Baron Murray M Chung Lorinda L Fierlbeck Gerhard G Lakshminarayanan Santhanam S Allanore Yannick Y Riemekasten Gabriela G Steen Virginia V Müller-Ladner Ulf U Spotswood Helen H Burke Laura L Siegel Jeffrey J Jahreis Angelika A Furst Daniel E DE Pope Janet E JE

Rheumatology (Oxford, England) 20180101 1

<h4>Objectives</h4>Patient acceptable symptom state (PASS) as an absolute state of well-being has shown promise as an outcome measure in many rheumatologic conditions. We aimed to assess whether PASS may be effective in active diffuse cutaneous SSc differentiating active from placebo.<h4>Methods</h4>Data from the phase 2 Safety and Efficacy of Subcutaneous Tocilizumab in Adults with Systemic Sclerosis (faSScinate) trial were used, which compared tocilizumab (TCZ) vs placebo over 48 weeks followe ...[more]

PMID: 29077900

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Project description:BackgroundAbnormalities in lymphocyte surface markers and functions have been described in systemic sclerosis (SSc), but conflicting results abound, and these studies often examined patients with heterogeneous disease duration, severity, clinical phenotype, and concurrent immunosuppressive agents. We studied a clinically homogeneous group of early diffuse cutaneous SSc patients not exposed to immunosuppressive drugs who were enrolled in a clinical trial and compared their immune parameters to healthy control subjects.MethodsLymphocyte subsets were enumerated by multi-parameter flow cytometry of peripheral blood mononuclear cells at baseline visit. Production of the cytokines IL-4 and IL-17 was measured by intracellular flow cytometry following T cell activation.ResultsSSc patients had increased percentages of CD4+ T cells but lower percentages of CD8+ T cells versus controls. The CD28-negative population was expanded in SSc, in the CD4 subset. Striking expansion of CD319+ T cells was noted among the CD4+ cells, in which they were barely detectable in healthy subjects. Frequencies of IL-4 producing cells did not differ between SSc and controls, but expansion of IL-17 producing cells was observed in SSc. A higher proportion of CD319+ cells produced cytokines, compared to other CD4+ cells. Numbers of activated T cells, regulatory T cells, and B cells were similar in SSc and control groups. Circulating follicular helper but not peripheral helper T cells were slightly expanded in SSc.ConclusionIn this carefully selected group of early diffuse cutaneous SSc patients, analysis of immune cell parameters has identified abnormalities that likely reflect disease pathogenesis and that are candidate biomarkers for sub-classification and targeted treatment. The CD4+CD319+ (SLAM-F7+) cells are cytotoxic and oligoclonal, were recently shown to be a dominant T cell population in perivascular lymphocytic infiltrates in SSc skin, actively secrete cytokines, and are emerging as a target for novel treatments of SSc.

Dataset Information

Patient acceptable symptom state in scleroderma: results from the tocilizumab compared with placebo trial in active diffuse cutaneous systemic sclerosis.

Publications

Patient acceptable symptom state in scleroderma: results from the tocilizumab compared with placebo trial in active diffuse cutaneous systemic sclerosis.

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