In this thesis, we aimed to assess outcomes of local disease activity in patients with rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) who received treatment-to-target, and to... Show moreIn this thesis, we aimed to assess outcomes of local disease activity in patients with rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) who received treatment-to-target, and to describe long-term clinical and radiographic outcomes in patients with treated-to-target RA. Show less
Spekking, K.; Anink, J.; Boer, P. de; Bergstra, S.A.; Berg, J.M. van den; Schonenberg-Meinema, D.; ... ; Muller, P.C.E.H. 2023
BackgroundThe aim of this study was to compare pain-scores in three targeted treatment-strategies in JIA-patients and to identify characteristics predicting persistent pain.MethodsIn the BeSt-for... Show moreBackgroundThe aim of this study was to compare pain-scores in three targeted treatment-strategies in JIA-patients and to identify characteristics predicting persistent pain.MethodsIn the BeSt-for-Kids-study 92 DMARD-naïve JIA-patients were randomized in 3 treatment-strategies: 1) initial sequential DMARD-monotherapy 2) initial methotrexate (MTX)/prednisolone-bridging or 3) initial MTX/etanercept. Potential differences in VAS pain scores (0-100 mm) over time between treatment-strategies were compared using linear mixed models with visits clustered within patients. A multivariable model was used to assess the ability of baseline characteristics to predict the chance of high pain-scores during follow-up.ResultsPain-scores over time reduced from mean 55.3 (SD 21.7) to 19.5 (SD 25.3) mm after 24 months. On average, pain-scores decreased significantly with β -1.37 mm (95% CI -1.726; -1.022) per month. No significant difference was found between treatment-strategies (interaction term treatment arm*time (months) β (95% CI) arm 1: 0.13 (-0.36; 0.62) and arm 2: 0.37 (-0.12; 0.86) compared to arm 3). Correction for sex and symptom duration yielded similar results. Several baseline characteristics were predictive for pain over time. Higher VAS pain [β 0.44 (95% CI 0.25; 0.65)] and higher active joint count [0.77 (0.19; 1.34)] were predictive of higher pain over time, whereas, low VAS physician [ -0.34 (-0.55; -0.06)], CHQ Physical [ -0.42 (-0.72; -0.11)] and Psychosocial summary Score [ -0.42 (-0.77; -0.06)] were predictive of lower pain.ConclusionsTreatment-to-target seems effective in pain-reduction in non-systemic JIA-patients irrespective of initial treatment-strategy. Several baseline-predictors for pain over time were found, which could help to identify patients with a high risk for development of chronic pain. Show less
Spekking, K.; Anink, J.; Boer, P. de; Bergstra, S.A.; Berg, J.M. van den; Schonenberg-Meinema, D.; ... ; Muller, P.C.E.H. 2023
BackgroundThe aim of this study was to compare pain-scores in three targeted treatment-strategies in JIA-patients and to identify characteristics predicting persistent pain.MethodsIn the BeSt-for... Show moreBackgroundThe aim of this study was to compare pain-scores in three targeted treatment-strategies in JIA-patients and to identify characteristics predicting persistent pain.MethodsIn the BeSt-for-Kids-study 92 DMARD-naïve JIA-patients were randomized in 3 treatment-strategies: 1) initial sequential DMARD-monotherapy 2) initial methotrexate (MTX)/prednisolone-bridging or 3) initial MTX/etanercept. Potential differences in VAS pain scores (0-100 mm) over time between treatment-strategies were compared using linear mixed models with visits clustered within patients. A multivariable model was used to assess the ability of baseline characteristics to predict the chance of high pain-scores during follow-up.ResultsPain-scores over time reduced from mean 55.3 (SD 21.7) to 19.5 (SD 25.3) mm after 24 months. On average, pain-scores decreased significantly with β -1.37 mm (95% CI -1.726; -1.022) per month. No significant difference was found between treatment-strategies (interaction term treatment arm*time (months) β (95% CI) arm 1: 0.13 (-0.36; 0.62) and arm 2: 0.37 (-0.12; 0.86) compared to arm 3). Correction for sex and symptom duration yielded similar results. Several baseline characteristics were predictive for pain over time. Higher VAS pain [β 0.44 (95% CI 0.25; 0.65)] and higher active joint count [0.77 (0.19; 1.34)] were predictive of higher pain over time, whereas, low VAS physician [ -0.34 (-0.55; -0.06)], CHQ Physical [ -0.42 (-0.72; -0.11)] and Psychosocial summary Score [ -0.42 (-0.77; -0.06)] were predictive of lower pain.ConclusionsTreatment-to-target seems effective in pain-reduction in non-systemic JIA-patients irrespective of initial treatment-strategy. Several baseline-predictors for pain over time were found, which could help to identify patients with a high risk for development of chronic pain. Show less
Background Methotrexate (MTX) therapy has proven to be a successful and safe treatment for Juvenile Idiopathic Arthritis (JIA). Despite the high efficacy rates of MTX, treatment outcomes are often... Show moreBackground Methotrexate (MTX) therapy has proven to be a successful and safe treatment for Juvenile Idiopathic Arthritis (JIA). Despite the high efficacy rates of MTX, treatment outcomes are often complicated by burdensome gastro-intestinal side effects. Intolerance rates for MTX in children are high (approximately 50%) and thus far no conclusive effective treatment strategies to control for side effects have been found. To address this need, this article proposes an innovative research approach based on pharmacological conditioning, to reduce MTX intolerance. Presentation of the hypothesis A collaboration between medical psychologists, pediatric rheumatologists, pharmacologists and patient groups was set up to develop an innovative research design that may be implemented to study potential improved control of side effects in JIA, by making use of the psychobiological principles of pharmacological conditioning. In pharmacological conditioning designs, learned positive associations from drug therapies (conditioning effects) are integrated in regular treatment regimens to maximize treatment outcomes. Medication regimens with immunosuppressant drugs that made use of pharmacological conditioning principles have been shown to lead to optimized therapeutic effects with reduced drug dosing, which might ultimately cause a reduction in side effects. Testing the hypothesis This research design is tailored to serve the needs of the JIA patient group. We developed a research design in collaboration with an interdisciplinary research group consisting of patient representatives, pediatric rheumatologists, pharmacologists, and medical psychologists. Show less
Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease that principally affects synovial joints. RA is present in 0,5% to 1% of the global population. The incidence of RA is higher in... Show moreRheumatoid arthritis (RA) is a chronic, systemic autoimmune disease that principally affects synovial joints. RA is present in 0,5% to 1% of the global population. The incidence of RA is higher in women than in men and increases with age (1). RA can affect any joint but preferably small joints in hands and feet (2). The symptoms of RA include pain, swelling, stiffness, redness, warmth and can finally lead to loss of joint functions (2). The systemic symptoms of RA include fatigue, malaise, loss of appetite and muscle ache. Next to the joints RA can affect other organs such as skin, lungs, heart and blood vessels (3). RA can be classified using the 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for rheumatoid arthritis (2010 ACR/EULAR criteria) (4). This is a quantitative system in which scores can be obtained from: joint involvement, serologic markers, inflammation markers and duration of symptoms (4). Show less
Juvenile idiopathic arthritis (JIA) is a non-common disease in children that can persist into adulthood. JIA is considered to be an auto-immune disease. Genetic factors play a role in the... Show moreJuvenile idiopathic arthritis (JIA) is a non-common disease in children that can persist into adulthood. JIA is considered to be an auto-immune disease. Genetic factors play a role in the pathogenesis. In a new cohort of JIA patients from North-West European descent genetic candidate gene association studies have been performed. In this cohort we have discovered new associations with the susceptibility of JIA and the genes/loci TRAF1/C5, 4q27, CD226 and CD28. These genes have already been associated with other auto-immune diseases and might be part of a shared common auto-immune susceptibility. Also genetic association with the course of disease has been studied, revealing an association of VTCN1 and the severity of JIA defined by the percentage of active disease in the first two years. VTCN1 encodes B7-H4 that is involved in the co-stimulation of T-cells and inhibits the immune-response. Until the precise role of VTCN1 will be clarified, the genetic association might be of use in predicting the course of disease and might be a lead point for new treatment. Show less
Hemke, R.; Nusman, C.M.; Heijde, D.M.F.M. van der; Doria, A.S.; Kuijpers, T.W.; Maas, M.; Rossum, M.A.J. van 2015
This thesis describes clinical and immunological aspects of immunoablative therapy followed by reinfusion of T-cell depleted autologous stem cells in patients with progressive refractory Juvenile... Show moreThis thesis describes clinical and immunological aspects of immunoablative therapy followed by reinfusion of T-cell depleted autologous stem cells in patients with progressive refractory Juvenile Idiopathic Arthritis (JIA). After an intensive immunoablative therapy in order to eradicate auto-agressive T cells, autologous hematopoietic stem cells of bone marrow, purged of potentially autoreactive mature T lymphocytes, were reinfused as rescue to reduce the aplastic phase after autologous stem cell transplantation (ASCT). Chapter 1 addresses the background and rationale leading to this study. Chapter 2 describes the safety, efficacy, complications and long term clinical outcome after ASCT in 22 patients with JIA, who were refractory to conventional medication. In chapter 3 the efficacy and safety of ASCT in 34 JIA patients transplanted in 9 different centers in Europe were evaluated. In chapter 4 the immunological effects of the conditioning on cellular infiltrates and expression of cytokines in the synovial tissue of two JIA patients were studied before and 6 months after ASCT. The subject of chapter 5 of this thesis is macrophage activation syndrome in systemic JIA patients. The actual effect of conditioning in vivo and graft manipulation ex vivo on the intended elimination of the adaptive (auto)immunological memory after ASCT was studied in 19 JIA/systemic lupus erythematodes (SLE) and 10 multiple sclerosis (MS) patients (chapter 7). In order to obtain reference values for anti-rabies specific humoral and cellular immune responses after a single and booster vaccination, we conducted a study in 18 healthy controls as described in chapter 6. Show less
