This thesis explores several different aspects of systemic sclerosis, including the role of sex hormones and insulin, the contribution of smoking to disease manifestations, and the applications of... Show moreThis thesis explores several different aspects of systemic sclerosis, including the role of sex hormones and insulin, the contribution of smoking to disease manifestations, and the applications of autologous haematopoietic stem cell transplantation. In this thesis we have analysed data from the prospective Leiden systemic sclerosis cohort, from an Italian cohort and also from patients of the multinational EUSTAR registry. The first part of this thesis is focused on hormones, in particular we revised the overall knowledge about sex hormones and we investigated the association between estrogens and development of microangiopathy. Then we analysed insulin sensitivity in systemic sclerosis patients and how it changes according to the different characteristics of the disease. In the second part, the main topic is cigarette smoking. We evaluated the effects of smoking on the risk of developing the disease, on organ progression and on autoantibody expression. We also assessed longitudinally how changes in respiratory parameters affected quality of life of SSc patients. The third part is on treatment strategies. We assessed the efficacy of HSCT in modifying the evolution of lung involvement and in improving microvascular damage. Finally, we described the changes in the prescription of SSc therapies over the last 10 years. Show less
This thesis consists of studies aiming to answer questions regarding the pathophysiology (ie. the role of antiglycoprotein antibodies) and treatment options (such as romiplostim and eltrombopag) in... Show moreThis thesis consists of studies aiming to answer questions regarding the pathophysiology (ie. the role of antiglycoprotein antibodies) and treatment options (such as romiplostim and eltrombopag) in immune thrombocytopenia (ITP). Furthermore, it gives examples of initiatives for implementation of PROMs in the ITP population. Show less
Webers, C.; Nikiphorou, E.; Boonen, A.; Ramiro, S. 2022
Biological disease-modifying antirheumatic drugs (bDMARDs) have taken up an important role in the management of axial spondyloarthritis. Once stable remission or low disease activity has been... Show moreBiological disease-modifying antirheumatic drugs (bDMARDs) have taken up an important role in the management of axial spondyloarthritis. Once stable remission or low disease activity has been achieved with bDMARDs, it may be possible to maintain this state with lower levels of these drugs. Studies consis-tently demonstrate that tapering of tumor necrosis factor alpha inhibitors (TNFi) is not inferior to full-dose continuation in terms of maintaining treatment response, while data for tapering of interleukin-17 inhibi-tors (IL-17i) is lacking. Complete discontinuation of TNFi and IL-17i, however, often results in relapse and should not be recommended at this moment. Clear safety benefits of tapering or discontinuation have not been shown, although studies were typically not designed to address this. Current evidence does not sup-port specific tapering or discontinuation strategies, although stepwise disease activity-guided regimens do allow for a more personalized approach and might be preferred. The definition of what constitutes an appropriate disease state to initiate tapering or discontinuation is unclear, and requires further study. Also, reliable predictors of successful tapering and discontinuation have not yet been identified. Fortuna-tely, if tapering or discontinuation fails, most patients are able to regain disease control when reverted to the original bDMARD regimen. Finally, most patients indicate that, when asked, they would be willing to try tapering if the rationale is clear and if it is in their best interests. The decision to taper or discontinue should be made through shared decision-making, as this could improve the likelihood of success. (c) 2022 Les Auteurs. Publie par Elsevier Masson SAS au nom de Societe franc,aise de rhumatologie. Cet article est publie en Open Access sous licence CC BY-NC-ND (http://creativecommons.org/licenses/by-nc-nd/4.0/). Show less
Mulligen, E. van; Weel, A.E.A.M.; Kuijper, T.M.; Hazes, J.M.W.; Helm-van Mil, A.H.M. van der; Jong, P.H.P. de 2020
Objectives: To determine the impact of a disease flare on patient reported outcome measures (PROMs) in rheumatoid arthritis (RA) patients, who are tapering treatment.Methods: Data were used from... Show moreObjectives: To determine the impact of a disease flare on patient reported outcome measures (PROMs) in rheumatoid arthritis (RA) patients, who are tapering treatment.Methods: Data were used from the TARA trial; a multicenter, randomized controlled trial in which RA patients, with a well-controlled disease (DAS <= 2.4 and SJC <= 1) for at least 6 months, gradually tapered their DMARDs. PROMs of patients with a flare (DAS>2.4 and/or SJC>1) were compared every three months before and after a flare with their own norm values. Linear Mixed Models were used to investigate whether a disease flare influenced functional ability (HAQ-DI), fatigue (BRAF-MDQ), quality of life (EQ-5D and SF36), anxiety and depression (HADS), morning stiffness, general health (GH) and worker productivity, and if so, the duration was determined. For unemployment and sick leave we used descriptive statistics.Results: A flare negatively influenced GH, morning stiffness, HAQ-DI, EQ-5D, BRAF-MDQ and the SF36 physical component scale and this effect lasted >3 months. Except for the HAQ-DI, effect sizes exceeded the minimum clinically important differences (MCIDs). For the physical outcomes effects lasted >6 months. Worker productivity was not significantly affected by a flare.Conclusion: A disease flare influenced patients' lives, the largest effect was seen in the physical outcomes, and lasted 6 months. Although on a group level effect sizes for the separate PROMs were not always significant or larger than specific MCIDs, a disease flare can still be of great importance for individual patients. (C) 2020 The Author(s). Published by Elsevier Inc. Show less
Michielsens, C.A.J.; Boers, N.; Broeder, N. den; Wenink, M.H.; Maas, A. van der; Mahler, E.A.M.; ... ; Broeder, A.A. den 2020
Background Tumour necrosis factor inhibitors (TNFi) are effective in the treatment of patients with spondyloarthritis (SpA), including psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA).... Show moreBackground Tumour necrosis factor inhibitors (TNFi) are effective in the treatment of patients with spondyloarthritis (SpA), including psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). However, these drugs come with some disadvantages such as adverse events, practical burden for patients and high costs. Dose optimisation of TNFi after patients have reached low disease activity (LDA) has been shown feasible and safe in rheumatoid arthritis (RA). However, data on TNFi dose optimisation in PsA and axSpA are scarce, especially pragmatic, randomised strategy studies. Methods We developed an investigator-driven, pragmatic, open-label, randomised, controlled, non-inferiority trial (DRESS-PS) to compare the effects of a disease activity-guided treat-to-target strategy with or without a tapering attempt in patients with SpA (PsA and axSpA combined), >= 16 years of age, who are being treated with TNFi, and have had at least 6 months of low disease activity. The primary outcome is the percentage of patients in LDA after 12 months of follow up. Patients are assessed at baseline, 3, 6, 9, and 12 months of follow up. Bayesian power analyses with a weakened prior based on a similar study performed in RA resulted in a sample size of 95 patients in total. Discussion More knowledge on disease activity-guided treatment algorithms would contribute to better treatment choices and cost savings and potentially decrease the risk of side effects. In this article we elucidate some of our design choices on TNFi dose optimisation and its clinical and methodological consequences. Show less
