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Roosendaal, Netherlands

Heimans L.,Leiden University | Wevers-de Boer K.V.C.,Leiden University | Visser K.,Leiden University | Goekoop R.J.,Haga Hospital | And 9 more authors.
Annals of the Rheumatic Diseases | Year: 2014

Objectives To assess which treatment strategy is most effective in inducing remission in early (rheumatoid) arthritis. Methods 610 patients with early rheumatoid arthritis (RA 2010 criteria) or undifferentiated arthritis (UA) started treatment with methotrexate (MTX) and a tapered high dose of prednisone. Patients in early remission (Disease Activity Score <1.6 after 4 months) tapered prednisone to zero and those with persistent remission after 8 months, tapered and stopped MTX. Patients not in early remission were randomised to receive either MTX plus hydroxychloroquine plus sulfasalazine plus low-dose prednisone (arm 1) or to MTX plus adalimumab (ADA) (arm 2). If remission was present after 8 months both arms tapered to MTX monotherapy; if not, arm 1 changed to MTX plus ADA and arm 2 increased the dose of ADA. Remission rates and functional and radiological outcomes were compared between arms and between patients with RA and those with UA. Results 375/610 (61%) patients achieved early remission. After 1 year 68% of those were in remission and 32% in drug-free remission. Of the randomised patients, 25% in arm 1 and 41% in arm 2 achieved remission at year 1 (p<0.01). Outcomes were comparable between patients with RA and those with UA. Conclusions Initial MTX and prednisone resulted in early remission in 61% of patients with early (rheumatoid) arthritis. Of those, 68% were in remission and 32% were in drug-free remission after 1 year. In patients not in early remission, earlier introduction of ADA resulted in more remission at year 1 than first treating with disease-modifying antirheumatic drug combination therapy plus prednisone. Source

Klarenbeek N.B.,Leiden University | Guler-Yuksel M.,Leiden University | Van Der Kooij S.M.,Leiden University | Han K.H.,Maasstad Hospital | And 7 more authors.
Annals of the Rheumatic Diseases | Year: 2011

Objective To compare clinical and radiological outcomes of four dynamic treatment strategies in recent-onset rheumatoid arthritis (RA) after 5 years follow-up. Methods 508 patients with recent-onset RA were randomly assigned into four treatment strategies: sequential monotherapy; step-up combination therapy; initial combination with prednisone; initial combination with infliximab. Treatment adjustments were made based on 3-monthly disease activity score (DAS) measurements (if DAS >2.4 next treatment step; if DAS ≤2.4 during ≥6 months taper to maintenance dose; if DAS <1.6 during ≥6 months stop antirheumatic treatment). Primary and secondary outcomes were functional ability, joint damage progression, health-related quality of life and (drug-free) remission percentages. Results After 5 years, 48% of patients were in clinical remission (DAS <1.6) and 14% in drug-free remission, irrespective of initial treatment. After an earlier improvement in functional ability and quality of life with initial combination therapy, from 1 year onwards clinical outcomes were comparable across the groups and stable during 5 years. The initial combination groups showed less joint damage in year 1. In years 2-5 annual progression was comparable across the groups. After 5 years, initial combination therapy resulted in significantly less joint damage progression, reflecting the earlier clinical response. Conclusion Irrespective of initial treatment, an impressive improvement in clinical and radiological outcomes of RA patients can be achieved with dynamic treatment aimed at reducing disease activity, leading to 48% remission, 14% drug-free remission and sustained functional improvement. Starting with combination therapy resulted in earlier clinical improvement and less joint damage without more toxicity. Source

Visser K.,Leiden University | Goekoop-Ruiterman Y.P.M.,Haga Hospital | De Vries-Bouwstra J.K.,VUmc | Ronday H.K.,Haga Hospital | And 5 more authors.
Annals of the Rheumatic Diseases | Year: 2010

Objectives: To develop a matrix model for the prediction of rapid radiographic progression (RRP) in subpopulations of patients with recent-onset rheumatoid arthritis (RA) receiving different dynamic treatment strategies. Methods: Data from 465 patients with recent-onset RA randomised to receive initial monotherapy or combination therapy were used. Predictors for RRP (increase in Sharp-van der Heijde score ≥5 after 1 year) were identified by multivariate logistic regression analysis. For subpopulations, the estimated risk of RRP per treatment group and the number needed to treat (NNT) were visualised in a matrix. Results: The presence of autoantibodies, baseline C-reactive protein (CRP) level, erosion score and treatment group were significant independent predictors of RRP in the matrix. Combination therapy was associated with a markedly reduced risk of RRP. The positive and negative predictive values of the matrix were 62% and 91%, respectively. The NNT with initial combination therapy to prevent one patient from RRP with monotherapy was in the range 2-3, 3-7 and 7-25 for patients with a high, intermediate and low predicted risk, respectively. Conclusion: The matrix model visualises the risk of RRP for subpopulations of patients with recent-onset RA if treated dynamically with initial monotherapy or combination therapy. Rheumatologists might use the matrix for weighing their initial treatment choice. Source

Van Der Veldt A.A.M.,University Medical Center | Van Der Veldt A.A.M.,VU University Amsterdam | Lubberink M.,University Medical Center | Lubberink M.,Uppsala University Hospital | And 13 more authors.
Clinical Cancer Research | Year: 2013

Purpose: Pharmacokinetics of docetaxel can be measured in vivo using positron emission tomography (PET) and a microdose of radiolabeled docetaxel ([11C]docetaxel). The objective of this study was to investigate whether a [11C]docetaxel PET microdosing study could predict tumor uptake of therapeutic doses of docetaxel. Experimental Design: Docetaxel-näve lung cancer patients underwent 2 [11C]docetaxel PET scans; one after bolus injection of [11C]docetaxel and another during combined infusion of [11C]docetaxel and a therapeutic dose of docetaxel (75 mgm 2). Compartmental and spectral analyses were used to quantify [11C]docetaxel tumor kinetics. [11C]docetaxel PET measurements were used to estimate the area under the curve (AUC) of docetaxel in tumors. Tumor response was evaluated using computed tomography scans. Results: Net rates of influx (Ki) of [11C]docetaxel in tumors were comparable during microdosing and therapeutic scans. [11C]docetaxel AUCTumor during the therapeutic scan could be predicted reliably using an impulse response function derived from the microdosing scan together with the plasma curve of [11C]docetaxel during the therapeutic scan. At 90 minutes, the accumulated amount of docetaxel in tumors was less than 1% of the total infused dose of docetaxel. [11C]docetaxel Ki derived from the microdosing scan correlated with AUCTumor of docetaxel (Spearman r = 0.715; P = 0.004) during the therapeutic scan and with tumor response to docetaxel therapy (Spearman r = 0.800; P = 0.010). Conclusions: Microdosing data of [11C]docetaxel PET can be used to predict tumor uptake of docetaxel during chemotherapy. The present study provides a framework for investigating the PET microdosing concept for radiolabeled anticancer drugs in patients. © 2013 American Association for Cancer Research. Source

Hofstra J.M.,Radboud University Nijmegen | Branten A.J.W.,Radboud University Nijmegen | Wirtz J.J.J.M.,Laurentius Hospital | Noordzij T.C.,Franciscus Hospital | And 2 more authors.
Nephrology Dialysis Transplantation | Year: 2010

Background. Immunosuppressive therapy in idiopathic membranous nephropathy (iMN) is debated. Accurate identification of patients at high risk for end-stage renal disease (ESRD) allows early start of therapy in these patients. It is unknown if early start of therapy is more effective andor less toxic than late start (i.e. when GFR deteriorates).Methods. We conducted a randomized open-label study in patients with iMN, a normal renal function and a high risk for ESRD (urinary β2m >0.5 μgmin, UIgG >125 mg day). Patients started with immunosuppressive therapy (cyclophosphamide for 12 months, and steroids) either immediately after randomization or when renal function deteriorated (ΔsCr ≥+25 and sCr >135 μmoll or ΔsCr ≥+50). End points were remission rates, duration of the nephrotic syndrome (NS), renal function and complications.Results. The study included 26 patients (24 M2 F), age 48 ± 12 years; sCr 96 μmoll (range 68-126) and median proteinuria 10.0 g10 mmol Cr. Early treatment resulted in a more rapid onset of remission (P = 0.003) and a shorter duration of the NS (P = 0.009). However, at the end of the follow-up (72 ± 22 m), there were no differences in overall remission rate, sCr (93 versus 105 μmoll), proteinuria, relapse rate and adverse events.Conclusions. In high-risk patients with iMN, immunosuppressive treatment is effective in inducing a remission. Early treatment shortens the duration of the nephrotic phase, but does not result in better preservation of renal function. Our study indicates that treatment decisions must be based on risk and benefit assessment in the individual patient. Source

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