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Contains fulltext : 190755.pdf (publisher's version ) (Closed access), BACKGROUND: A considerable disease period often precedes initiation of a biologic in patients with psoriasis. Little is known about this important period in patients' lives. Evaluation of this 'journey' can reveal important insights and opportunities for physicians and healthcare decision makers. OBJECTIVES: (i) To describe patient and treatment characteristics until the start of biologic treatment in patients with severe psoriasis, (ii) to assess shifts in early (2005-2009) versus established (2010-2015) biologics prescription periods, (iii) to assess changes in hospital/day care admissions before vs. after starting biologics. METHODS: Explorative, retrospective study on the treatment characteristics of the disease period until first biologic, presented with descriptive statistics of patients included in the BioCAPTURE registry. Journeys of 2005-2009 and 2010-2015 were compared with statistical tests to identify important shifts. RESULTS: Median TUS (time until conventional systemic) was 11.0 years and median TUB (time until biologic) was 18.9 years for all patients treated from 2005 to 2015. Most patients received three different conventional antipsoriatic systemic therapies. We noticed a small trend towards a shorter journey (TUB) with only two conventional systemic agents instead of three before initiating a biologic in later years (2010-2015, vs. 2005-2009). We also noticed a significant decrease in (day care) admissions comparing the two years before, versus the first two years after the start of a biologic treatment (17.7 vs. 8.6 admissions/100 follow-up years, P < 0.001). Cyclosporine, intensive topical treatment (dithranol), retinoids and PUVA therapy lost popularity in recent years. CONCLUSION: The 'journey' of patients with psoriasis towards a biologic is still long and characterized by many different treatments. Shifts towards fewer conventional drugs before biologic initiation and a clear decrease in hospital and day care admissions before vs. after a b

Contains fulltext : 190724.pdf (publisher's version ) (Closed access)

Contains fulltext : 151801.pdf (publisher's version ) (Closed access), BACKGROUND: Drug survival is an indicator for treatment success; insight in predictors associated with drug survival is important. OBJECTIVES (I): To analyse the long-term drug survival for adalimumab in patients with psoriasis treated in daily practice and (II) to identify predictors of prolonged drug survival for adalimumab split for different reasons of discontinuation. METHODS: Data were extracted from a prospective psoriasis cohort and analysed using Kaplan-Meier survival curves split for reasons of discontinuation. Baseline predictors associated with longer drug survival were identified using multivariate Cox-regression analysis. RESULTS: One hundred and sixteen patients were included with a total of 208 patient-years. Overall drug survival was 76% after 1 year and 52% after 4.5 years. In patients who stopped due to ineffectiveness, longer drug survival was associated with the absence of specific comorbidities (P = 0.03). In patients who stopped due to side-effects, longer drug survival was associated with male gender (P = 0.02). CONCLUSIONS: Predictors of adalimumab drug survival in psoriasis differ by reason for discontinuation. Strong, specific predictors can lead to patient-tailored treatment.

Item does not contain fulltext, OBJECTIVE: To investigate if there was a difference in time to the occurrence of first non-melanoma skin cancer (NMSC) and in the incidence of NMSC between psoriasis patients and rheumatoid arthritis (RA) patients on TNF inhibitors. DESIGN: Prospective observational cohort study. METHOD: We compared the time to first NMSC (expressed as hazard ratio) and the incidence of NMSC (expressed as incidence ratio) in psoriasis and RA patients in the Netherlands who were treated with TNF inhibitors and had a follow-up of at least one year. Cox regression and Poisson regression analyses were used; both were corrected for confounders (age, gender, disease duration, prior NMSC, duration of anti-TNF and other systemic therapies). RESULTS: The NMSC risk was significantly higher in the psoriasis group (fully adjusted hazard ratio: 6.0 [1.6 - 22.4 95% CI]) and time to first NMSC in psoriasis compared with RA was also shorter (1.6 years and 3.7 years, respectively). The incidence of NMSC was 5.5 times higher in psoriasis patients (2.2 - 13.4 95% CI) than in those with RA. CONCLUSION: The time to first NMSC was significantly shorter and the incidence of NMSC was significantly higher in psoriasis than in RA. This indicates that disease-related factors such as phototherapy may be important contributing factors to the occurrence of NMSC in psoriasis patients treated with TNF inhibitors.

Contains fulltext : 151809.pdf (publisher's version ) (Closed access), BACKGROUND: Concerns exist about a risk of non-melanoma skin cancer (NMSC) in psoriasis patients and rheumatoid arthritis (RA) patients treated with TNF-inhibitors. However, current data also show that in some psoriasis patients, NMSC is diagnosed relatively short after the start of TNF-inhibitors, which suggests that these NMSC can be explained by previous therapies instead of by TNF-inhibitor therapy. OBJECTIVE: To investigate whether there was a difference in time until first NMSC and the rate of NMSC between psoriasis and RA patients on TNF-inhibitors. METHODS: Time until first NMSC and the rate of NMSC were compared between psoriasis and RA patients from the same region treated with TNF-inhibitors and followed up for at least one year in prospective cohort studies, by using Cox regression and Poisson regression. Both analyses were corrected for confounders (age, gender, disease duration, prior NMSC, duration of anti-TNF and other systemic therapies). RESULTS: The NMSC risk was significantly higher in the psoriasis group [fully adjusted HR 6.0 (1.6-22.4 95%CI)] with a shorter time until first NMSC in psoriasis compared to RA. By Poisson regression, psoriasis patients had a 5.5 (2.2-13.4 95%CI) higher rate of NMSC. CONCLUSION: The time until first NMSC was significantly shorter and the rate of NMSC was significantly higher in psoriasis compared with RA. This indicates that disease-related factors like phototherapy may be important contributing factors to NMSC diagnosed in psoriasis patients treated with TNF-inhibitors.

Radboud Universiteit Nijmegen, 25 maart 2014, Promotor : Kerkhof, P.C.M. van de Co-promotor : Jong, E.M.G.J. de, Contains fulltext : 125137.pdf (publisher's version ) (Open Access)

Contains fulltext : 138289.pdf (publisher's version ) (Closed access), BACKGROUND: Auto-immune inflammatory rheumatic diseases (AIRD) are often successfully treated with the immunosuppressant azathioprine for years. Treatment with azathioprine has been proven to increase the risk of non-melanoma skin cancer (NMSC) in transplant patients and possibly in patients with inflammatory bowel disease as well. Little is known about the risk of NMSC in AIRD patients treated with azathioprine. OBJECTIVES: The aim of this study is to determine the incidence of NMSC in patients with AIRD treated with azathioprine for at least 1 year, as compared with the general Dutch population. METHODS: Data were extracted from a historical cohort of patients with AIRD in a tertiary care centre. We compared the incidence to an age-matched control population and analysed risk factors for NMSC with univariate logistic regression. RESULTS: Fifty-nine patients were analysed. No patients were diagnosed with basal cell carcinoma and four patients with a single squamous cell carcinoma (SCC). Patients with SCC had a higher cumulative dose of azathioprine (>/= 500 g: OR 30.0 [95% CI 2.6-345.1]) and longer treatment duration (>/= 11 years: OR 13.5 [95% CI 1.3-143.6]). The risk of SCC compared with the general Dutch population was increased (standardized incidence ratio of 16.0 [95% CI 0.3-31.7]). CONCLUSIONS: In this cohort of patients with AIRD treated with azathioprine for at least 1 year, the risk of SCC was increased, as compared with the general population. An individual cumulative dose of at least 500 g azathioprine and a treatment duration of at least 11 years were quantified as risk factors.

Contains fulltext : 137761.pdf (publisher's version ) (Closed access), BACKGROUND: Long-term data of etanercept drug survival in patients with psoriasis in daily practice are scarce. OBJECTIVES: The primary objective was to describe drug survival for etanercept in a long-term daily practice cohort of patients with psoriasis. The secondary objective was to identify determinants of drug survival for etanercept in general and separately for discontinuation due to adverse events or ineffectiveness of therapy. METHODS: Data were extracted from a prospective daily practice cohort of patients treated with biologics for psoriasis. Drug survival was analysed by Kaplan-Meier survival curves and split for two reasons for discontinuation: adverse events and ineffectiveness. Determinants of drug survival were analysed using univariate Cox regression analysis and multivariate Cox regression analysis with backward selection. RESULTS: We included 193 patients (512 patient-years treated) with a maximum treatment duration of 7.5 years. The overall drug survival rates were 77%, 41% and 30% after 1, 4 and 7.5 years, respectively. The mean survival duration was 3.8 years (95% confidence interval 3.4-4.3). Reasons for discontinuation were ineffectiveness (33.7%), adverse events (11.9%), both ineffectiveness and adverse events (4.7%) or other reasons (e.g. pregnancy planned) (5.7%). Determinants related to longer general drug survival were male sex [hazard ratio (HR) 0.55], prior anti-tumour necrosis factor (TNF)-alpha use (HR 0.57) and lower etanercept dose (HR 0.65). Younger age (HR 0.83), lower body mass index (HR 0.63) and lower etanercept dose (HR 0.71) were related to a decreased risk of discontinuation due to side-effects. A lower mean weekly dose of etanercept (HR 0.63) was related to a decreased risk of discontinuation due to ineffectiveness of therapy. CONCLUSIONS: We present the longest analysis of drug survival for etanercept in psoriasis to date. Determinants of longer overall etanercept drug survival were male sex, prior anti-TNF therapy and lo