Vasco C Romão1, Frances Humby2, Stephen Kelly3, Maria Di Cicco2, Arti Mahto2, Ilias Lazarou2, Rebecca Hands2, Vidalba Rocher-Ros2, Désirée van der Heijde4, João Eurico Fonseca5, Costantino Pitzalis6. 1. Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK; Department of Rheumatology, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, Lisbon Academic Medical Centre; Av. Prof. Egas Moniz, 1649-035 Lisbon, Portugal; Rheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028, Lisbon, Portugal. 2. Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK. 3. Rheumatology Department, Mile End Hospital, Barts Health NHS Trust, 275 Bancroft Road, London E1 2DG, UK. 4. Department of Rheumatology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands. 5. Department of Rheumatology, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, Lisbon Academic Medical Centre; Av. Prof. Egas Moniz, 1649-035 Lisbon, Portugal; Rheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028, Lisbon, Portugal. 6. Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK. Electronic address: c.pitzalis@qmul.ac.uk.
Abstract
BACKGROUND: Clinical outcomes in elderly-onset rheumatoid arthritis (EORA), starting after the age of 60, are conflicting. Thus, we aimed to investigate in a unique biopsy-driven, treatment-naïve early arthritis cohort, the relationship between synovial pathobiology of elderly- (EORA) and younger-onset rheumatoid arthritis (YORA) patients through clinical, imaging and treatment response outcome-measures. METHODS: Patients (n = 140) with early RA (<12months) starting before (YORA, n = 99) or after (EORA, n = 41) age 60 had an ultrasound-guided synovial biopsy prior to conventional immunosuppressive therapy and after 6 months. Clinical, ultrasound and radiographic data were collected prospectively and compared between groups and against immunohistological features. Using multivariate logistic regression, we determined predictors of clinical response (disease activity score-28-erythrocyte sedimentation rate [DAS28-ESR]<3.2) at 6 months and radiographic progression (≥1-unit-increase in Sharp van der Heijde [SvdH] score) at 12 months. RESULTS: EORA patients were more frequently male and presented most commonly with an abrupt, polymyalgia rheumatica-like onset and extra-articular features. Both before and after treatment, DAS28-ESR was similar but ultrasound synovial-thickening (p<0.05) and power-Doppler (p<0.01) synovitis and SvdH (p<0.001) scores were higher in EORA patients. EORA was independently associated with poor treatment response at 6 months (OR=0.28, p = 0.047) and radiographic progression at 12 months (OR=4.08, p = 0.029). Synovial pathotype, synovitis scores and cellular infiltration were similar before treatment, but a pauci-immune-fibroid pathotype tended to be more common in YORA at 6 months (p = 0.093). Moreover, YORA patients had a marked improvement of all synovitis parameters (p<0.001), whereas EORA presented only mild decreases in synovitis (p<0.05), sublining macrophage (p<0.05) and T cell scores (p<0.05), with no significant changes in lining macrophages, B cells or plasma cells. CONCLUSION: Early EORA presents differently and has a worse overall prognosis than YORA, with poorer clinical, histological, ultrasonographic and radiographic outcomes.
BACKGROUND: Clinical outcomes in elderly-onset rheumatoid arthritis (EORA), starting after the age of 60, are conflicting. Thus, we aimed to investigate in a unique biopsy-driven, treatment-naïve early arthritis cohort, the relationship between synovial pathobiology of elderly- (EORA) and younger-onset rheumatoid arthritis (YORA) patients through clinical, imaging and treatment response outcome-measures. METHODS:Patients (n = 140) with early RA (<12months) starting before (YORA, n = 99) or after (EORA, n = 41) age 60 had an ultrasound-guided synovial biopsy prior to conventional immunosuppressive therapy and after 6 months. Clinical, ultrasound and radiographic data were collected prospectively and compared between groups and against immunohistological features. Using multivariate logistic regression, we determined predictors of clinical response (disease activity score-28-erythrocyte sedimentation rate [DAS28-ESR]<3.2) at 6 months and radiographic progression (≥1-unit-increase in Sharp van der Heijde [SvdH] score) at 12 months. RESULTS: EORA patients were more frequently male and presented most commonly with an abrupt, polymyalgia rheumatica-like onset and extra-articular features. Both before and after treatment, DAS28-ESR was similar but ultrasound synovial-thickening (p<0.05) and power-Doppler (p<0.01) synovitis and SvdH (p<0.001) scores were higher in EORA patients. EORA was independently associated with poor treatment response at 6 months (OR=0.28, p = 0.047) and radiographic progression at 12 months (OR=4.08, p = 0.029). Synovial pathotype, synovitis scores and cellular infiltration were similar before treatment, but a pauci-immune-fibroid pathotype tended to be more common in YORA at 6 months (p = 0.093). Moreover, YORA patients had a marked improvement of all synovitis parameters (p<0.001), whereas EORA presented only mild decreases in synovitis (p<0.05), sublining macrophage (p<0.05) and T cell scores (p<0.05), with no significant changes in lining macrophages, B cells or plasma cells. CONCLUSION: Early EORA presents differently and has a worse overall prognosis than YORA, with poorer clinical, histological, ultrasonographic and radiographic outcomes.