Calcinosis Working Group Update

Calcinosis Working Group Update

SCTC Business Meeting ACROctober 26, 2013

Lorinda Chung

Calcinosis

Multi-disciplinary International Effort

• Rheumatology• Radiology• Dermatology

• US• UK• Europe• Canada• Australia• Turkey• Mexico

Research Agenda• Evaluation of frequency, incidence, and associated

clinical features• Development of radiographic scoring system• Development of patient reported outcome measure for

clinically apparent calcinosis • Development of classification system• Development of physical exam measurements of

calcinosis burden• Studies to understand pathophysiologic mechanisms

underlying development of calcinosis

Progress• Evaluation of frequency, incidence, and

associated clinical features– Antonia Valenzuela

• Development of radiographic scoring system– Lorinda Chung

• Development of patient reported outcome measure for clinically apparent calcinosis– Lesley Saketkoo

• Development of classification system– Vivien Hsu

Frequency of calcinosis

• “Frequency of calcinosis in a multi-center international cohort of patients with Systemic Sclerosis: A Scleroderma Clinical Trials Consortium Study”– Presented at the 13th Scleroderma Research

Workshop August 2013 in Boston, MA– Data from electronic survey answered by 16

centers

Frequency of calcinosis• Overall frequency of calcinosis of 22% in a multi-

center international cohort of 7056 SSc patients. – 17% in patients with diffuse cutaneous SSc– 25% in patients with limited cutaneous SSc– 28% in patients with systemic sclerosis sine

scleroderma

• Patients with calcinosis had longer mean disease duration from the first non-Raynaud’s symptom than those without

Valenzuela A, Cuomo G, Sutton E, Gordon J, Spiera R, Rodriguez-Reyna T, Proudman S, et al. Frequency of calcinosis in a multicenter international cohort of patients with Systemic Sclerosis: A Scleroderma Clinical Trials Consortium Study. 13 th Scleroderma Research Workshop. Boston, US, August 3-7, 2013.

Next steps

• “Incidence of calcinosis and identification of associated risk factors in a multi-center international collaborative study of patients with Systemic Sclerosis: A Scleroderma Clinical Trials Consortium Study”

Incidence of calcinosis

• Specific Aims:1. To determine the cumulative incidence of calcinosis

in patients with SSc. 2. To assess for an association between clinical features

and specific autoantibodies and the subsequent development of calcinosis in patients with SSc.

– Disease duration and maximum mRSS – Digital ulcers, pulmonary arterial hypertension, or

scleroderma renal crisis – Anti-centromere, RNA polymerase III, and anti-beta (2)-

glycoprotein I antibodies

Incidence of calcinosis

• Methods:– Retrospective cohort study including patients with

SSc enrolled in each study location database. – We will collect demographics, dates of diagnosis,

clinical features and autoantibody information.

Incidence of calcinosis• Study Locations:

– Stanford University School of Medicine, Palo Alto, CA, US– Hospital for Special Surgery, New York, NY, US– Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico

City, Mexico– Royal Adelaide Hospital, Adelaide, Australia– St Vincent's Hospital, Melbourne, Australia– Rutgers-RWJMS Scleroderma Program, New Brunswick, NJ, US– A.O.U. of Cagliari, Cagliari, Italy– Istanbul University, Istanbul, Turkey– Jewish General Hospital, Montreal, QC, Canada– University of Pittsburgh Medical Center, Pittsburgh, PA, US– University of Manchester, Salford Royal NHS Foundation Trust, Salford, UK– University of Texas Health Science Center at Houston, Houston, Texas, US– Northwestern University Feinberg School of Medicine, Chicago, IL, US

Validation of a Novel Radiographic Scoring System for Calcinosis Affecting the Hands of Patients with Systemic Sclerosis

Lorinda Chung1, Antonia Maria Valenzuela Vergara1, David Fiorentino1, Kate Stevens1, Shufeng Li1, Jonathan Harris2, Charles Hutchinson3, Shervin Assassi4, Lorenzo Beretta5,

Santhanam Lakshminarayanan6, Tatiana Rodriguez Reyna7, Christopher P. Denton8, Rebecca G. Taillefer9, Solene Tatibouet10, Ariane Herrick11, Murray Baron10 on behalf of

the Scleroderma Clinical Trials Consortium Calcinosis Working Group1Stanford University School of Medicine, 2Salford Royal Hospital, 3University of Warwick, 4University of Texas in Houston, 5Policlinico di Milano, 6University of Connecticut School of Medicine, 7Instituto Nacional de Ciencias

Médicas y Nutrición Salvador Zubirán, 8Royal Free Hospital, 9University of Montreal, 10McGill University, 11University of Manchester

ACR, Oct 27, 2013: Poster 679

Radiographic Scoring System

OBJECTIVE• To develop and validate a novel radiographic

scoring system for calcinosis affecting the hands of patients with SSc for potential use in future clinical trials

Radiographic Scoring System

• Methods– 12 investigators• 8 rheumatologists• 1 dermatologist• 3 radiologists

– Rating of 12 hand radiographs using a simple and complex scoring system• Re-scoring of 2 XR at least 24 hours later

– Assessment of inter- and intra-rater reliability

Simple Scoring System

• Mild—single site of low density• Moderate—medium density at one or more sites OR a single site of high

density• Severe—more than one site of high or mixed density

Johnstone et al. Rheumatology. 2012; 51(12):2234-8.

Complex Scoring System

Sum of scores for 22 weighted areas affecting each hand:% area coverage (0-100) X density (1-3) X weight for each area

ReliabilitySIMPLE SCORING SYSTEM KAPPA (95% CI)

OVERALL INTER-RATER 0.39 (0.1-0.52)

DICHOTOMIZED INTER-RATER* 0.51 (0.26-0.7)

INTRA-RATER# 0.67 (0.37-0.96)

COMPLEX SCORING SYSTEM ICC (95% CI)

INTER-RATER 0.89 (0.86-0.92)

INTRA-RATER 0.93 (0.89-0.97)

*Dichotomized mild/moderate vs. severe#One rater only re-scored one XR

Calcinosis: PROM• Content Collection: 5 Focus Groups

– Atlanta, New Orleans, New York, San Diego– 18 Participants

• Initial Strategies: – Item Collection to Saturation (or 30 )– Proceed with content validation, Q development, factor anal

• Preliminary Data Review:– Anticipate confounding elements in content– Strongly disparate as well as unifying concepts– Suggestive of >1 process / general experience of calcinosis– Calcinosis not well understood at basic level

• Relinquish timeline on goal-oriented PROM development• Continue focus on exploration of patient perspective

– Carefully characterize important differences– Perhaps accommodating distinct groups

Next Steps

Calcinosis Working Group Meeting – Aqua 308 8:30-9:30 PM

Agenda• Present and finalize protocol on incidence and

associated clinical features of calcinosis:– Antonia Valenzuela Vergara

• Discuss further development of patient focus groups for patient reported outcome measure: – Lesley Saketkoo

• Present and discuss classification of calcinosis: – Vivien Hsu