Drug Survival, Safety, and Effectiveness of Biologics in Older Patients with Psoriasis: A Comparison with Younger Patients-A BioCAPTURE Registry Study.

BACKGROUND: Psoriasis is a common inflammatory disease in any age group, but also in older patients (≥ 65 years of age). Since older patients are often excluded from clinical trials, limited data specifically on this growing population are available, e.g. regarding the safety and performance of biological treatment. AIMS: We aimed to give insight into this specific population by comparing the drug survival and safety of biologics in older patients with that in younger patients. METHODS: In this real-world observational study, data from 3 academic and 15 non-academic centers in The Netherlands were extracted from the prospective BioCAPTURE registry. Biologics included in this study were tumor necrosis factor (TNF)-α, interleukin (IL)-17, IL-12/23, and IL-23 inhibitors. Patients were divided into two age groups: ≥ 65 years and < 65 years. The Charlson Comorbidity Index (CCI) was used to measure comorbid disease status, and all adverse events (AEs) that led to treatment discontinuation were classified according to the Medical Dictionary for Regulatory Activities (MedDRA) classification. All AEs that led to treatment discontinuation were studied to check whether they could be classified as serious AEs (SAEs). Kaplan-Meier survival curves for overall 5-year drug survival and split according to reasons of discontinuation (ineffectiveness or AEs) were constructed. Cox regression models were used to correct for possible confounders and to investigate associations with drug survival in both age groups separately. Psoriasis Area and Severity Index (PASI) scores during the first 2 years of treatment and at the time of treatment discontinuation were assessed and compared between age groups. RESULTS: A total of 890 patients were included, of whom 102 (11.4%) were aged ≥ 65 years. Body mass index, sex, and distribution of biologic classes (e.g. TNFα, IL12/23) were not significantly different between the two age groups. A significantly higher CCI score was found in older patients, indicative of more comorbidity (p < 0.001). The 5-year ineffectiveness-related drug survival was lower for older patients (44.5% vs. 60.5%; p = 0.006), and the 5-year overall (≥ 65 years: 32.4% vs. < 65 years: 42.1%; p = 0.144) and AE-related (≥ 65 years: 82.1% vs. < 65 years: 79.5%; p = 0.913) drug survival was comparable between age groups. Of all AEs (n = 155) that led to discontinuation, 16 (10.3%) were reported as SAEs but these only occurred in younger patients. After correcting for confounders, the same trends were observed in the drug survival outcomes. Linear regression analyses on PASI scores showed no statistical differences at 6, 12, 18, and 24 months of treatment between age groups. CONCLUSIONS: This study in a substantial, well-defined, prospective cohort provides further support that the use of biologics in older patients seems well-tolerated and effective. Biologic discontinuation due to AEs did not occur more frequently in older patients. Older patients discontinued biologic treatment more often due to ineffectiveness, although no clear difference in PASI scores was observed. More real-world studies on physician- and patient-related factors in older patients are warranted.

Female patients are less satisfied with biological treatment for psoriasis and experience more side-effects than male patients: results from the prospective BioCAPTURE registry.

BACKGROUND: Female sex has been reported as a predictor for treatment discontinuation with biological therapies for psoriasis, although reasons remain unclear. It can be hypothesized that lower satisfaction with biological treatment in women might add to the lower drug survival rates. OBJECTIVES: To identify possible differences in satisfaction with biological treatment between female and male patients using the Treatment Satisfaction Questionnaire for Medication (TSQM). METHODS: Data of psoriasis patients treated with biologics were obtained from the prospective, multicentre, daily-practice BioCAPTURE registry. Longitudinal TSQM data were analysed by linear mixed models. Relevant patient characteristics were incorporated as possible confounding factors. Post hoc analysis of adverse events was performed in order to investigate differences between sexes. RESULTS: We included 315 patients with 396 corresponding treatment episodes (137 adalimumab, 90 etanercept, 137 ustekinumab, 24 secukinumab and 8 infliximab). Almost forty per cent of the patients were female. Women had significantly lower baseline PASI scores (P = 0.01). Longitudinal analyses demonstrated lower TSQM scores for 'side-effects' (P = 0.05) and 'global satisfaction' (P = 0.01) in female patients compared with male patients over 1 year of treatment. Women reported more relevant adverse events in the context of biologic treatment compared to men (rate ratio 1.79; P < 0.001), with more fungal (rate ratio 2.20; P = 0.001) and herpes simplex infections (rate ratio 3.25; P = 0.005). CONCLUSIONS: This study provides a prospective, longitudinal analysis of treatment satisfaction with biologics in female and male patients with psoriasis. Women were slightly less satisfied with treatment regarding side-effects and global satisfaction. Differences in treatment satisfaction and side-effects might add to the fact that women discontinue biological treatments more often.

The journey of adult psoriasis patients towards biologics: past and present - Results from the BioCAPTURE registry.

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 biologic are seen. Improvement of this journey, especially in young or recently diagnosed patients, can decrease negative influences on patients' lives and reduce societal impact.

Comparison of the 1- and 5-year effectiveness of adalimumab, etanercept and ustekinumab in patients with psoriasis in daily clinical practice: results from the prospective BioCAPTURE registry.

BACKGROUND: The efficacy of etanercept and ustekinumab in psoriasis has been compared in one randomized controlled trial. Comparison of the long-term effectiveness of biologics in daily-practice psoriasis treatment is currently lacking. OBJECTIVES: To compare the effectiveness between the three widely used outpatient biologics adalimumab, etanercept and ustekinumab in daily-practice psoriasis treatment and to correct for confounders. METHODS: Data were extracted from the prospective, multicentre BioCAPTURE registry. Multilevel linear regression analyses (MLRAs) and generalized estimating equation (GEE) analyses were performed on the course of mean Psoriasis Area and Severity Index (PASI) and PASI 75 (≥ 75% reduction vs. baseline). Both models were corrected for confounders. Subgroup analyses for biological dose were performed. RESULTS: We included 356 patients with 513 treatment episodes: 178 adalimumab, 245 etanercept and 90 ustekinumab. MLRA showed a similar effectiveness between adalimumab, etanercept and ustekinumab after 1 year, but the highest effectiveness for ustekinumab during 5 years of treatment (P = 0·047; ustekinumab vs. etanercept, P = 0·019). GEE analysis revealed a higher chance of attaining PASI 75 with adalimumab and ustekinumab than with etanercept at 1 year of treatment. A higher than label dose was more often used in patients treated with etanercept (adalimumab, etanercept and ustekinumab: respectively 31·5%, 55·1% and 17% after 1 year, P < 0·001; 39·3%, 71·4% and 24% after 5 years, P < 0·001). CONCLUSIONS: Compared with etanercept, ustekinumab had the highest effectiveness during 5 years of treatment. Patients receiving adalimumab and ustekinumab more often reached PASI 75 than those on etanercept at 1 year of treatment. Dose escalation was more frequent in etanercept and adalimumab than in ustekinumab.

Body mass index predicts discontinuation due to ineffectiveness and female sex predicts discontinuation due to side-effects in patients with psoriasis treated with adalimumab, etanercept or ustekinumab in daily practice: a prospective, comparative, long-term drug-survival study from the BioCAPTURE registry.

BACKGROUND: Predictors for successful treatment are important for personalized medicine. Predictors for drug survival of biologics in psoriasis have been assessed, but not split for different biologics or for the reason of discontinuation. OBJECTIVES: To compare long-term drug survival between the outpatient biologics adalimumab, etanercept and ustekinumab in patients with psoriasis, and to elucidate predictors for overall survival and drug discontinuation due to ineffectiveness and side-effects for each biologic separately. METHODS: Ten years of data were extracted from the prospective, multicentre, long-term BioCAPTURE registry. Kaplan-Meier survival analyses and confounder-corrected multivariate Cox regression analysis for drug survival (MCR-DS) were performed to compare drug survival between biologics. To elucidate the predictors for different reasons of discontinuation for each biologic, univariate Cox regression analyses and multivariate Cox regression analyses for predictors (MCR-P) with backward selection were performed. RESULTS: In total, 526 treatment episodes - 186 adalimumab, 238 etanercept and 102 ustekinumab - were included covering 1333 treatment years. MCR-DS showed a significantly higher overall survival for ustekinumab compared with adalimumab and etanercept. MCR-P showed that higher body mass index (BMI) was a predictor for discontinuation due to ineffectiveness for etanercept and ustekinumab and that female sex was a predictor for discontinuation due to side-effects for adalimumab, etanercept and ustekinumab. CONCLUSIONS: Ustekinumab has the highest confounder-corrected long-term drug survival in psoriasis treatment, compared with adalimumab and etanercept. Higher BMI is a predictor for discontinuation due to ineffectiveness in etanercept and ustekinumab, and female sex is a consistent predictor for discontinuation due to side-effects in all three outpatient biologics.

Safety of treatment with biologics for psoriasis in daily practice: 5-year data.

BACKGROUND: The cumulative exposition to biologics is increasing with prolonged treatment with a certain biologic or consecutive biological treatment. However, long-term safety data are limited available. OBJECTIVES: The aim of this study was to prospectively evaluate the 5-year safety of biological treatment for psoriasis in daily practice. METHODS: A cohort of 173 psoriasis patients on biologics was prospectively followed for 5 years. All adverse events reported were documented and analysed. Primary endpoint was the percentage of patients reporting at least one serious adverse event. The rate of malignancies, serious infections and serious cardiovascular events was compared with the general population incidence rate. The nature and rate of dermatological adverse events was compared with a group of prospectively followed rheumatoid arthritis patients on TNF-α blocking therapy. RESULTS: Between February 2005 and April 2010, 173 patients were enrolled in the registry and went through a total number of 263 treatment episodes. The total number of patient-years of follow-up in the registry was 409. The number of patient-years was the highest for etanercept. Forty-nine patients (28%) reported 88 serious adverse events. Only one serious adverse event was certainly causally related to the biologic and 21 events (24% of SAEs) were considered possibly related. The incidence of malignancies, serious infections and serious cardiovascular events was comparable with the population incidence rate, except for skin malignancies. The incidence of skin malignancies was significantly higher than the general population incidence rate. The nature and rate of dermatological adverse events differed from the rheumatoid arthritis cohort. CONCLUSIONS: In this cohort, the safety of biological therapies for psoriasis was favourable with a low incidence of therapy-related serious adverse events.

Relevance of compartmentalization of T-cell subsets for clinical improvement in psoriasis: effect of immune-targeted antipsoriatic therapies.

BACKGROUND: Therapies targeting the T cell-mediated pathology of psoriasis have been found to achieve remarkable clinical improvement and have confirmed the crucial role of the immune system either in peripheral blood (PB) or in skin. No analyses of T-cell counts in both compartments have been conducted in order to confirm or refute the hypothesized shifts between them. OBJECTIVES: To gain more insight in the dynamics of compartmentalization of T cells between PB and lesional skin of patients with psoriasis, in response to immune-targeted antipsoriatic therapies. METHODS: Eighteen patients with psoriasis received either efalizumab (n = 9) or etanercept (n = 9) for 12 weeks. Biopsies were taken for immunohistochemical analysis of T-cell subsets and simultaneously T-cell subsets were isolated from PB specimens by flow cytometry. RESULTS: The Psoriasis Area and Severity Index declined significantly after 12 weeks of etanercept, but not for efalizumab. After treatment with efalizumab, a significantly decreased number of all T-cell subsets was found in the dermis. In the epidermis, CD4+, CD8+, CD25+, CD45RO+ and CD161+ T-cell subsets were significantly decreased. With respect to etanercept, few significant changes in T-cell subsets were found. The percentage of lymphocytes in PB was significantly elevated after efalizumab treatment regardless of responder status. CONCLUSIONS: Treatment with efalizumab establishes successful recompartmentalization of T-cell subsets with modest clinical efficacy after 12 weeks, whereas in etanercept-treated patients, a significant clinical response is no guarantee for significant changes in T-cell subsets in the different compartments. Reductions in T-cell subsets cannot be used as predictive markers for the clinical response to therapy. Interference with the studied T-cell populations in its own right seems not to be responsible for the clinical efficacy of efalizumab and etanercept.

Psoriasis treatment with etanercept and efalizumab: clinical strategies influencing treatment outcome.

BACKGROUND: Multiple trials have been conducted in which the safety and efficacy of different biological therapies for psoriasis have been studied. However, the treatment course in clinical practice is different from the setting in which trials are conducted. OBJECTIVES: The evaluation of the efficacy, safety and adverse events of etanercept and efalizumab treatment in daily practice and the investigation of interfering clinical strategies that could be of influence on treatment outcome. METHODS: A prospective cohort consisting of 101 patients with high-need psoriasis was followed for 2 years and analysed. Patients were treated with etanercept or efalizumab between February 2005 and May 2007. Efficacy, safety and adverse events were investigated. Furthermore, all accompanying factors of which an influence on treatment efficacy outcome was suspected were registered, including treatment interruptions, dosage adjustments and combinations of therapies. RESULTS: Etanercept and efalizumab treatment was effective and safe in most patients. However, in many cases the treatment course was characterized by unsatisfactory efficacy (83%), necessitating combination therapies or dosage adjustments. Treatment interruptions occurred in 56% (etanercept 2x50 mg group), 84% (etanercept 2x25 mg group) and 10% (efalizumab-treated patients). CONCLUSIONS: Treatment of high-need psoriasis patients in daily practice is highly different from treatment courses in clinical trials. Frequently applied clinical strategies such as treatment interruptions, dosage adjustments and combinations of treatments influence treatment outcome in routine treatment in comparison with randomized controlled trials. Information about treatment with these new drugs in daily clinical practice is important for adjusting treatment schedules and guidelines.

Dermatologists' adherence to the guideline of the Dutch Society of Dermatology and Venereology with respect to the treatment with methotrexate for severe chronic plaque psoriasis: results from a Dutch survey.

BACKGROUND: In 2003, the Dutch guideline 'Photo(chemo) therapy and systemic therapy for severe chronic plaque psoriasis' was established. OBJECTIVES: To document how closely this guideline is followed in clinical practice with respect to the methotrexate (MTX) treatment and to formulate recommendations to adjust the guideline. METHODS: A survey was conducted among Dutch dermatologists and residents in dermatology. The questionnaire assessed the knowledge of and the adherence to the guideline with respect to MTX treatment. RESULTS: Fifty percent of the contacted dermatologists/residents responded. Fifty-two percent follow the guideline with respect to MTX. Liver biopsy and the frequency of blood investigations cause a discrepancy between guideline and reality. There is a lack of consensus between guidelines of the different specialisms concerning liver biopsy. CONCLUSION: The need for liver biopsies in combination with the frequent check-ups and the lack of consensus between rheumatologists, hepatologists and dermatologists seem to restrict the adherence to the guideline.

Liver injury in long-term methotrexate treatment in psoriasis is relatively infrequent.

BACKGROUND: Methotrexate-induced liver damage in psoriasis has led to dermatologic guidelines that stipulate monitoring of liver injury by means of serial liver biopsies. Recent literature data suggest that methotrexate may be considerably less hepatotoxic than previously assumed. AIM: To evaluate prevalence and development of liver injury in methotrexate treated psoriasis. METHODS: Retrospective chart review (1976-2005). RESULTS: Hundred and twenty-five patients (F58/M67; mean age 45.0, SD 12.7 years) received a median cumulative methotrexate dose of 2,113 mg (range 180-20 235) over a median period of 228 weeks (range 16-1763). Two hundred and seventy eight liver biopsies were analysed and 71% were classified as Roenigk grade I, 14% as Roenigk II, 14% grade IIIa, 2% grade IIIB and 2% grade IV. Liver injury was not associated with cumulative dose, weekly prescribed dose, age or duration of treatment. Obesity and diabetes were significant risk factors for liver injury. A total of 68 patients had multiple biopsies, 3% improved, 72% did not change and in 25% liver histology deteriorated. The majority of cases (84%) that progressed to Roenigk 2 had a cumulative dose of 1,500-6,000 mg. CONCLUSIONS: Methotrexate-related liver injury is less frequent than previously thought and mostly occurred at cumulative dose of <6,000 mg. Diabetes and being overweight are significantly correlated with liver injury.