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.

Determinants for drug survival of methotrexate in patients with psoriasis, split according to different reasons for discontinuation: results of the prospective MTX-CAPTURE.

BACKGROUND: As methotrexate (MTX) is a widely used treatment for psoriasis, it is important to gain insight into the reasons for the discontinuation of MTX and to understand the determinants for drug survival. OBJECTIVES: To describe 5-year drug survival for MTX in patients with psoriasis, split according to different reasons for discontinuation, and to identify the determinants for drug survival. METHODS: Data were extracted from a prospective psoriasis registry of patients treated with MTX (MTX-CAPTURE). Drug survival was analysed using Kaplan-Meier estimates and the determinants for discontinuation were analysed using Cox regression analysis. Analyses were split according to the reason for discontinuation: side-effects or ineffectiveness. RESULTS: We included 85 patients treated with MTX, with a maximum treatment duration of 5·2 years. The overall drug survival rates were 63%, 30% and 15% after 1, 3 and 5 years, respectively. The median survival was 1·8 years. Overall, 55 patients (65%) discontinued MTX for the following reasons: side-effects (35%), ineffectiveness (26%), combination of side-effects and ineffectiveness (13%), other reasons (16%) and 11% were lost to follow-up. The most reported side-effects were gastrointestinal symptoms, despite the use of folic acid in 99% of patients. Based on univariate analysis, a high Psoriasis Area and Severity Index score and a high score on the visual analogue scale for disease severity at baseline were possible determinants for a short drug survival. CONCLUSIONS: Drug survival of MTX was low with 15% of patients 'on drug' after 5 years. Side-effects alone or in combination with inadequate disease control were more important in the context of treatment discontinuation than inadequate disease control alone.

Validation of the Simplified Psoriasis Index in Dutch children and adolescents with plaque psoriasis.

BACKGROUND: The Simplified Psoriasis Index (SPI) is a three-domain assessment measure for psoriasis, including separate indicators of current severity (SPI-s), psychosocial impact (SPI-p), and past history and interventions (SPI-i). There are two complementary versions available designed for completion by a health professional (proSPI) or by patient self-assessment (saSPI). The validity and reliability of the proSPI vs. saSPI have already been demonstrated in adults. To date, validated severity measures for paediatric psoriasis do not exist. OBJECTIVES: To validate the current severity (SPI-s) and psychosocial impact (SPI-p) domains of the proSPI and saSPI in children and adolescents with psoriasis. METHODS: All patients aged < 18 years with plaque psoriasis visiting the dermatology outpatient department of Radboud University Medical Center, the Netherlands, between September 2013 and April 2014 were asked to complete Dutch versions of the saSPI and the Children's Dermatology Life Quality Index (CDLQI). The original English versions of the proSPI and Psoriasis Area and Severity Index (PASI) were completed by the physician at the same visit. RESULTS: In total, 113 patients (median age 12·0 years, range 4-17) were included. There was a close correlation between the proSPI-s and PASI (r = 0·87), which was higher than between the saSPI-s and PASI (r = 0·69). The correlation between the SPI-p and CDLQI was 0·78. The full range of scores was utilized in both proSPI-s and SPI-p, although the highest saSPI-s score was 30 (maximum 50). CONCLUSIONS: In paediatric psoriasis, the proSPI and saSPI are shown to be valid and usable. The SPI-s and SPI-p can be readily introduced into routine clinical practice.

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.

Frequency and predictors of a high clinical response in patients with psoriasis on biological therapy in daily practice: results from the prospective, multicenter BioCAPTURE cohort.

BACKGROUND: It is important to assess which patients with psoriasis are more likely to achieve high clinical responses on biologics. OBJECTIVES: To assess the number of treatment episodes (TEs) that achieve a 100% improvement in Psoriasis Area and Severity Index (PASI 100), PASI 90 or PASI ≤ 5 at week 24 of biological treatment, and which baseline patient characteristics predict treatment response. METHODS: Data from patients with psoriasis treated with adalimumab, etanercept, infliximab or ustekinumab were extracted from a prospective cohort. TEs with high clinical responses were described. Uni- and multivariate regression analyses were performed with the generalized estimating equation method to elucidate which baseline patient characteristics were predictors for PASI 90 and PASI ≤ 5 at week 24. RESULTS: In total, 454 TEs were extracted (159 adalimumab; 193 etanercept; 19 infliximab; 83 ustekinumab) from 326 patients. At week 24, in 3%, 15% and 59% of TEs, respectively, PASI 100, PASI 90 and PASI ≤ 5 was reached. In TEs without a PASI 100 or PASI 90 response, PASI ≤ 5 was still achieved in 58% and 52%, respectively. Baseline PASI ≥ 10 was a strong predictor for achieving PASI 90; baseline PASI < 10 and a lower baseline body mass index (BMI) were significant predictors for PASI ≤ 5 at week 24. CONCLUSIONS: A limited number of patients achieved PASI 100 or PASI 90 at 24 weeks of biological treatment. Including an absolute PASI score in the assessment of psoriasis severity is important. Baseline BMI was an important, modifiable predictor for a high response.

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.

A pilot study on the Psoriasis Area and Severity Index (PASI) for small areas: Presentation and implications of the Low PASI score.

BACKGROUND: The Psoriasis Area and Severity Index (PASI) is not able to measure small affected areas in a body region which is important for assessing the performance of high-effective treatment. OBJECTIVE: To present the Low PASI score, show the difference between the classic PASI and the Low PASI, evaluate the inter-observer agreement of both scores, and compare the two scores within investigators. METHODS: Cross-sectional study. Two investigators independently assessed the classic PASI and the Low PASI in 10 patients with mild-to-moderate plaque psoriasis. Differences in outcome between the two scores were calculated. Intra-class correlation coefficients (ICC) were used to determine the inter-observer agreement and to compare measurements of the two scores within both investigators. Prediction limits of 95% for the errors in measurements were provided. RESULTS: In both investigators, Low PASI was mean 1.71 and 1.76, whereas the classic PASI was mean 4.14 and 4.33. The inter-observer agreement (ICC) was excellent for both investigators in both scores (ICC classic PASI = 0.95 and Low PASI = 0.87). CONCLUSION: The Low PASI score allows more possible scores at lower levels of psoriasis extent (affected areas lower than 10% in a body region) compared to the classic PASI. This new score may lead to a more precise analysis of treatment responses and may have important clinical implications.

Comparing treatment goals for psoriasis with treatment decisions in daily practice: results from a prospective cohort of patients with psoriasis treated with biologics: BioCAPTURE.

BACKGROUND: Treatment goals have been developed to optimize daily clinical practice psoriasis care, but have not yet been studied in real life. OBJECTIVES: To investigate to what extent treatment decisions made by dermatologists in daily clinical practice for patients with psoriasis on biologics are already in accordance with treatment goals without the active application of the treatment goals algorithm. METHODS: Data were extracted from a prospective daily practice cohort of patients with psoriasis on biologics. Analysis was done on effectiveness (Psoriasis Area and Severity Index score) and quality of life (Dermatology Life Quality Index questionnaire). Treatment decisions such as dosage adjustments, combination treatments, or switching therapy were compared with the treatment goals algorithm. RESULTS: In 64% (253 of 395) of visits, physicians followed the treatment goals algorithm. There were 162 (41%) visits in which there should have been a treatment modification according to treatment goals (group Modify) and a modification was indeed made in 59 of these 162 visits (36%). In 233 (59%) visits no treatment modification was necessary (group Continue) and therapy was indeed not modified in 194 of 233 visits (83%). CONCLUSIONS: Physicians acted in accordance with treatment goals in the majority of patient visits. In the patient group not achieving these goals, physicians should have modified therapy according to treatment goals but continued the same therapeutic regimen in the majority of visits. Optimizing therapy and defining barriers in the latter group might increase treatment results in daily practice psoriasis care.

'Happy' drug survival of adalimumab, etanercept and ustekinumab in psoriasis in daily practice care: results from the BioCAPTURE network.

BACKGROUND: Drug survival is a marker for treatment success. To date, no analyses relating dermatological quality-of-life measures to drug survival have been published. OBJECTIVES: (i) To describe 1-year drug survival for adalimumab, etanercept and ustekinumab in a daily practice psoriasis cohort, and (ii) to introduce the concept of 'happy' drug survival, defined as Dermatology Life Quality Index (DLQI) ≤ 5 combined with being 'on drug' at a specific time point. METHODS: Data were extracted from a prospective registry. Drug survival was analysed using Kaplan-Meier estimates. 'Happy' drug survival was calculated, with data split into 'happy' (DLQI ≤ 5) vs. 'unhappy' (DLQI > 5) at baseline and months 3, 6, 9 and 12. RESULTS: 249 treatment episodes were included (101 adalimumab, 82 etanercept, 66 ustekinumab). The 1-year drug survival rates for ustekinumab, adalimumab and etanercept were 85%, 74% and 68%, respectively. Ustekinumab showed a better confounder-corrected drug survival vs. etanercept [hazard ratio (HR) 3·8, P = 0·02] and a trend towards better survival vs. adalimumab (HR 2·3, P = 0·1). At baseline, the majority (n = 115, 73%) was considered 'unhappy' and a minority 'happy' (n = 42, 27%) (ratio 'happy':'unhappy' was 1 : 2.7). The percentage of treatment episodes with 'happy' on-drug patients increased to 79% after 1 year. CONCLUSIONS: Ustekinumab showed a better overall drug survival than etanercept, and a trend towards a better overall drug survival than adalimumab. After 1 year, patients reported to be 'happy' in 79% of episodes and 'unhappy' in 21%. We introduced the new concept of 'happy' drug survival because the proportion of on-drug patients with good quality of life is an important indicator for treatment success.

Satisfaction of treatment with biologics is high in psoriasis: results from the Bio-CAPTURE network.

BACKGROUND: Although the effectiveness of biologics for psoriasis has been measured extensively with objective outcome measures, studies based on subjective, patient-reported outcome measures remain scarce. OBJECTIVES: To investigate satisfaction with medication, as measured by the Treatment Satisfaction Questionnaire for Medication (TSQM) for biologics in daily practice psoriasis care in the first 6 months of treatment; and to identify possible differences in satisfaction with medication between patients experienced (biologics-experienced) and inexperienced (biologics-inexperienced) in the use of biologics. METHODS: TSQM baseline measurements were compared using measurements taken after 6 months, using the Wilcoxon signed-rank test for paired comparisons. Intention-to-treat with last observation carried forward (ITT with LOCF) and as-treated analyses were performed. The difference between biologics-experienced and biologics-inexperienced patients for TSQM was analysed using ITT with LOCF. At 6 months, outcomes for biologics-experienced and biologics-inexperienced patients were compared using the Mann-Whitney U-test. RESULTS: One hundred and six patients were eligible for analysis, and treated with etanercept (n = 34), adalimumab (n = 49) or ustekinumab (n = 23). Fifty-four per cent of patients were biologics-inexperienced. A statistically significant improvement was seen in all domains of the TSQM ('effectiveness', 'side-effects', 'convenience' and 'global satisfaction') by comparison of months 3 or 6 with baseline (all P ≤ 0·02). After 6 months, biologics-inexperienced patients scored better on the 'global satisfaction' domain than biologics-experienced patients (P < 0·01). CONCLUSIONS: We provide a prospective, longitudinal analysis of TSQM for biologics in daily practice psoriasis care. High satisfaction rates were achieved. The 'effectiveness' and 'convenience' domains showed the most room for improvement.

Efficacy of blue light vs. red light in the treatment of psoriasis: a double-blind, randomized comparative study.

BACKGROUND: Protoporphyrin IX is present in psoriatic skin without the preceding application of aminolevulinic acid. Therefore, endogenous photosensitizers in psoriasis are a potential target for photodynamic treatment with high-dose visible light. OBJECTIVES: In the present pilot study, treatment with high-dose blue and red light in psoriasis were analysed with respect to clinical improvement and potential side-effects. METHODS: In 20 patients, two stable psoriatic plaques were treated with either blue or red light, three times weekly for four consecutive weeks. To remove scaling that could potentially interfere with penetration of the light into the skin, daily application of 10% salicylic acid in petrolatum was started at the screening visit and continued until the end of the study. RESULTS: Clinical improvement was seen after treatment with blue as well as after treatment with red light. With respect to scaling and induration, no major differences between both light sources were seen. Improvement of erythema, however, continued in blue light irradiated plaques throughout the whole study period, whereas after red light no significant improvement was seen after six illuminations. CONCLUSIONS: The clinical improvement of psoriasis, with respect to erythema, in particular after blue light and to a lesser extent after red light indicates that visible light treatment could represent a treatment option for psoriasis.

Oral retinoic acid metabolism blocking agent Rambazole for plaque psoriasis: an immunohistochemical study.

BACKGROUND: The novel systemic all-trans retinoic acid metabolism blocking agent (RAMBA) R115866 (Rambazole(TM); Barrier Therapeutics, Geel, Belgium; further referred to as rambazole) increases intracellular levels of endogenous all-trans retinoic acid (RA). Well-known effects of RA are normalization of aberrant epithelial growth and differentiation. Hence, rambazole might be beneficial in the treatment of plaque psoriasis. OBJECTIVES: The dynamics of epidermal proliferation, keratinization, lesional T-cell subsets and cells expressing natural killer (NK)-receptors in plaque psoriasis were assessed during treatment with rambazole, as part of a phase IIa open-label clinical trial. METHODS: Six patients were treated with rambazole, 1 mg, once daily, for 8 weeks. At weeks 0, 2 and 8, psoriatic plaque severity scores (SUM) and biopsies from a target lesion were assessed. Epidermal proliferation (Ki67), keratinization markers (K10, K13, K19), T-cell subsets (CD3, CD4+, CD8+, CD45RO+, CD45RA+, CD2+, CD25+, GITR+) and cells expressing NK-receptors (CD94, CD161) were immunohistochemically stained and quantified with image analysis. RESULTS: At week 2 the mean SUM-score was virtually equal to baseline, which was accompanied immunohistochemically by equal epidermal hyperproliferation, a nonsignificant decrease in K10 positive epidermis and, overall, a nonsignificant increase in immunocyte subsets. At week 8, in contrast, plaque severity was reduced by 34% from baseline (P < 0.05). Improvements were also detected for epidermal proliferation (-63%; P < 0.01) and K10 expression (+29%; P < 0.01), compared with baseline. No induction of retinoid-specific keratinization (K13, K19) was observed. A nonsignificant reduction of all pathogenic T-cell subsets and cells expressing NK-receptors was observed at week 8 of treatment (P > 0.05). CONCLUSIONS: Clinical efficacy of rambazole is primarily the result of restoring proliferation (Ki67) and differentiation (K10) of epidermal keratinocytes. Secondly, relevant T-cell subsets and cells expressing NK-receptors showed nonsignificant reductions after 8 weeks of treatment with rambazole.

Quality of life in vitiligo patients after treatment with long-term narrowband ultraviolet B phototherapy.

Long-term treatments for chronic diseases such as vitiligo need to be evaluated for their clinical efficacy. Assessment of the quality of life (QOL), however, may provide the most relevant information on the actual benefit for these patients. In this study we evaluated QOL after long-term narrowband ultraviolet (UV) B for the treatment of vitiligo. All patients, with long-term stable vitiligo vulgaris, who were treated at our clinic during the last 4 years received specifically for this study a designed QOL questionnaire, which included questions about general well-being, camouflage and psychosocial aspects; 71.4% of the patients responded. Most patients indicated an improvement on a psychological level, but an increase in camouflaging. The present study shows that, after long-term narrowband UVB phototherapy, skin appearance does not play a major role in the life of vitiligo patients, while well being only improved in a minority of patients.

VML 295 (LY-293111), a novel LTB4 antagonist, is not effective in the prevention of relapse in psoriasis.

Leukotriene B4 (LTB4) receptor antagonists have been the subject of several studies in the treatment of inflammatory diseases, including psoriasis. A novel oral LTB4 antagonist, VML 295 (LY-293111) has recently been developed and has a pronounced effect on epidermal inflammatory parameters. However, oral treatment of psoriasis for 4 weeks did not result in a decrease in disease severity. The present study was performed in order to investigate whether prolonged treatment with VML 295 up to 8 weeks has a beneficial effect on the overall severity of psoriasis. Moreover, we studied to what extent VML 295 is able to prevent relapse in psoriasis. In the present study, 35 patients with stable chronic plaque psoriasis were included. A representative plaque of at least 16 cm2 was initially treated with clobetasol-17-propionate lotion under hydrocolloid occlusion in all patients. Clearance was achieved within 6 weeks in 31 patients. After clearance, the patients were randomized to treatment and received oral VML 295 capsules 200 mg twice daily or placebo for 8 weeks. Twenty-five patients completed the study. The psoriasis area and severity index (PASI) was assessed before treatment, at clearance, and on days 15, 29, 43 and 5 7 of the treatment period. Biopsies were taken from the treated lesion before treatment, after clearance and at relapse, and cells were analysed by flow cytometry with markers for differentiation (keratin 10), inflammation (vimentin), and proliferation (DNA content). After 8 weeks of treatment, 14 of 15 VML 295-treated patients had relapsed and 11 of 16 placebo-treated patients had relapsed. A total of six patients were withdrawn. The time to relapse and the number of relapsed patients was not significantly different comparing the treatment groups. There was no significant difference in PASI scores between VML 295-treated patients and placebo-treated patients after 8 weeks of treatment. Flow cytometric parameters for differentiation, inflammation and proliferation did not show significant differences between VML 295- and placebo-treated patients. We conclude that oral VML 295 (LY-293111) is not effective in preventing relapse in psoriasis, either clinically or at the cellular level, and that in our group of patients VML 295 had no beneficial effect on overall psoriasis severity. Moreover, we conclude that further development of LTB4 modulating drugs for the treatment of psoriasis is not indicated.