Purpose To assess safety and effectiveness of anti-tumor necrosis factor (anti-TNF) therapy in IBD patients >= 60 years. Methods Ninety IBD patients >= 60 years at initiation of anti-TNF... Show morePurpose To assess safety and effectiveness of anti-tumor necrosis factor (anti-TNF) therapy in IBD patients >= 60 years. Methods Ninety IBD patients >= 60 years at initiation of anti-TNF therapy, 145 IBD patients >= 60 years without anti-TNF therapy and 257 IBD patients < 60 years at initiation of anti-TNF therapy were retrospectively included in this multicentre study. Primary outcome was the occurrence of severe adverse events (SAEs), serious infections and malignancies. Secondary outcome was effectiveness of therapy. Cox regression analyses were used to assess differences in safety and effectiveness. In safety analyses, first older patients with and without anti-TNF therapy and then older and younger patients with anti-TNF therapy were assessed. Results In older IBD patients, the use of anti-TNF therapy was associated with serious infections (aHR 3.920, 95% CI 1.185-12.973,p= .025). In anti-TNF-exposed patients, cardiovascular disease associated with serious infections (aHR 3.279, 95% CI 1.098-9.790,p= .033) and the presence of multiple comorbidities (aHR 9.138 (1.248-66.935),p= .029) with malignancies, while patient age did not associate with safety outcomes. Effectiveness of therapy was not affected by age or comorbidity. Conclusion Older patients receiving anti-TNF therapy have a higher risk of serious infections compared with older IBD patients without anti-TNF therapy, but not compared with younger patients receiving anti-TNF therapy. However, in anti-TNF-exposed patients, comorbidity was found to be an indicator with regards to SAEs. Effectiveness was comparable between older and younger patients. Show less
In this thesis, the results are described of a randomized multicenter treatment-to-target study in early-onset, non-systemic Juvenile Idiopathic Arthritis (JIA) with 2 years of follow-up. The... Show moreIn this thesis, the results are described of a randomized multicenter treatment-to-target study in early-onset, non-systemic Juvenile Idiopathic Arthritis (JIA) with 2 years of follow-up. The treatment arms consisted of 1) initial monotherapy with methotrexate or sulfasalazine, 2) initial treatment with methotrexate and prednisolone and 3) initial treatment with etanercept and MTX. If preset goals (ACRpedi50% after 3months and inactive disease from 6 months and onwards) were not met, therapy was adjusted with tight control. If inactive disease lasted at least 6 months, therapy was tapered and stopped. After three months of treatment, significantly more ACRPedi70% was found in arm 3. After two years of follow-up in all three arms approximately 70% of patients had reached inactive disease and up to 39% of patients was drug-free. Wrist radiographs of the patients did not show damage at the start of the study, nor during follow-up. The conclusions of this thesis are that inactive disease is a feasible goal in the treatment of JIA if treatment-to-target is applied with tight control. In our study, tight control seems more important than the initial medication. Tapering strategies can be applied in treatment-to-target strategies to reach drug-free inactive disease in JIA. Show less
Jacobse, J.; Voorde, W. ten; Rissmann, R.; Burggraaf, J.; Cate, R. ten; Schrier, L. 2019
Biopharmaceuticals are among the most celebrated drugs. However, despite decades of experience, our understanding of many in vivo pharmacokinetic and adverse effects of biopharmaceuticals is... Show moreBiopharmaceuticals are among the most celebrated drugs. However, despite decades of experience, our understanding of many in vivo pharmacokinetic and adverse effects of biopharmaceuticals is still limited. These include the delay in reaching the maximum plasma concentration for an intravenously administered therapeutical protein, and the highly variable plasma concentration during elimination of monoclonal antibodies. Both observations can be explained by dynamical binding (‘stickiness’) of proteins to various (bodily) surfaces. Biopharmaceuticals also frequently contain (non-human) impurities, some of which are harmful when administered (‘dirtiness’). This toxicity often is the result of an intricate interplay of multiple cell types and effector pathways which can be difficult to simulate in the laboratory. More sophisticated test platforms are available, which can detect a number of untoward reactions that would previously not have been discovered. However, no laboratory test is fail-safe, and awareness of the possibility of adverse immunostimulation caused by biopharmaceuticals is the most important aspect for early detection and prevention of such cases in the future. Show less
Muller, P.C.E.H.; Brinkman, D.M.C.; Schonenberg, D.; Koopman-Keemink, Y.; Brederije, I.C.J.; Bekkering, W.P.; ... ; Cate, R. ten 2017
