Background The multi-biomarker disease activity (MBDA) test measures 12 serum protein biomarkers to quantify disease activity in RA patients. A newer version of the MBDA score, adjusted for age,... Show moreBackground The multi-biomarker disease activity (MBDA) test measures 12 serum protein biomarkers to quantify disease activity in RA patients. A newer version of the MBDA score, adjusted for age, sex, and adiposity, has been validated in two cohorts (OPERA and BRASS) for predicting risk for radiographic progression. We now extend these findings with additional cohorts to further validate the adjusted MBDA score as a predictor of radiographic progression risk and compare its performance with that of other risk factors.MethodsFour cohorts were analyzed: the BRASS and Leiden registries and the OPERA and SWEFOT studies (total N =953). Treatments included conventional DMARDs and anti-TNFs. Associations of radiographic progression (Delta TSS) per year with the adjusted MBDA score, seropositivity, and clinical measures were evaluated using linear and logistic regression. The adjusted MBDA score was (1) validated in Leiden and SWEFOT, (2) compared with other measures in all four cohorts, and (3) used to generate curves for predicting risk of radiographic progression.ResultsUnivariable and bivariable analyses validated the adjusted MBDA score and found it to be the strongest, independent predicator of radiographic progression (Delta TSS >5) compared with seropositivity (rheumatoid factor and/or anti-CCP), baseline TSS, DAS28-CRP, CRP SJC, or CDAI. Neither DAS28-CRP, CDAI, SJC, nor CRP added significant information to the adjusted MBDA score as a predictor, and the frequency of radiographic progression agreed with the adjusted MBDA score when it was discordant with these measures. The rate of progression (Delta TSS >5) increased from <2% in the low (1-29) adjusted MBDA category to 16% in the high (45-100) category. A modeled risk curve indicated that risk increased continuously, exceeding 40% for the highest adjusted MBDA scores.ConclusionThe adjusted MBDA score was validated as an RA disease activity measure that is prognostic for radiographic progression. The adjusted MBDA score was a stronger predictor of radiographic progression than conventional risk factors, including seropositivity, and its prognostic ability was not significantly improved by the addition of DAS28-CRP, CRP, SJC, or CDAI. Show less
In this thesis we have pursued innovative analytical solutions for some of the most challenging questions in the field of SpA. We have gained better insights into the concept of axSpA by studying... Show moreIn this thesis we have pursued innovative analytical solutions for some of the most challenging questions in the field of SpA. We have gained better insights into the concept of axSpA by studying it independently of the rheumatologist’s opinion. Our findings likely add knowledge to what axSpA really is. Future studies will learn us how much of these insights will translate into a better recognition of the disease in clinical practice and in better classifying them for research purposes. Since SpA is a slowly progressing disease, several years are needed to see meaningful changes in imaging abnormalities of the axial skeleton, which poses methodological challenges. We have shown that thoughtful analytical approaches, that make best use of imaging data, are helpful in better estimating progression, in unravelling its determinants and in clarify which outcomes are best to monitor disease. Efforts are made to further improve outcome measurement in axSpA, including the development of new imaging techniques, which can benefit from our proposed solutions to long-term imaging scoring. Show less
Romao, V.C.; Humby, F.; Kelly, S.; Cicco, M. di; Mahto, A.; Lazarou, I.; ... ; Pitzalis, C. 2020
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-naive... Show moreBackground: 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-naive 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 6months and radiographic progression (>= 1-unit-increase in Sharp van der Heijde [SvdH] score) at 12months.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. (C) 2020 Elsevier Inc. All rights reserved. Show less
Landewe, R.B.M.; Connell, C.A.; Bradley, J.D.; Wilkinson, B.; Gruben, D.; Strengholt, S.; Heijde, D. van der 2016
Conclusion: Baseline structural damage and bone turnover activity, as reflected by BMLs, seem to be involved in knee OA progression. Moreover, progression in PFJ and TFJ seems to be related. (C)... Show moreConclusion: Baseline structural damage and bone turnover activity, as reflected by BMLs, seem to be involved in knee OA progression. Moreover, progression in PFJ and TFJ seems to be related. (C) 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. Show less
The ACPA response is different from conventional antibody responses. The ACPA response is generally of a much lower avidity than recall responses. Avidity maturation is limited and occurs before... Show moreThe ACPA response is different from conventional antibody responses. The ACPA response is generally of a much lower avidity than recall responses. Avidity maturation is limited and occurs before disease onset. The presence of low avidity ACPA is associated with higher rate of joint destruction. In vitro, the binding of low avidity ACPA to citrullinated epitopes was weakly inhibited by citrullinated antigens and low avidity ACPA have a higher ability to activate the complement system. In addition, there are certain antigens which continuously drive ACPA (IgM) response in RA. Show less
