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.

[A young man with discoloured nails]. / Een jonge man met verkleurde nagels.

A 23-year-old man consulted his general practitioner with discoloured nails. The nails showed the typical pattern of half and half nails or Lindsay's nails. This condition sometimes accompanies renal failure or thyroid disease and must be differentiated from Terry's nails, psoriatic nails and onychomycosis. Blood tests showed no underlying condition in this patient.

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.

Itch and scratching as predictors of time to clearance of psoriasis with narrow-band ultraviolet B therapy.

BACKGROUND: Narrow-band ultraviolet (UV) B phototherapy is an effective treatment for psoriasis. However, there is considerable variability in the number of treatment sessions needed to achieve psoriasis clearance. While several clinical and treatment-related factors predict time to clearance, the effect of itching and scratching on the number of irradiation sessions is insufficiently understood. OBJECTIVE: Predictors of the time to clearance were assessed in patients with psoriasis who were referred for UVB treatment in a randomized double-blind comparison of irradiation regimens for UVB phototherapy. METHODS: After randomization to either UVB irradiation with a suberythematogenic or an erythematogenic regimen, patients were irradiated with 20% and 40% incremental doses, respectively, three times weekly. The Psoriasis Area and Severity Index (PASI) score was measured at baseline and every 4 weeks, and itching and habitual scratching were measured at baseline. RESULTS: Among the 77 patients who achieved psoriasis clearance (90% reduction of PASI), itching and scratching were correlated with the number of irradiation sessions needed to achieve clearance, with higher levels of itch and scratching predicting more sessions. These effects remained significant after controlling for the initial PASI score, irradiation schemes, minimal erythema dose (MED), skin type, cumulative dose, protocol adjustments and lifestyle factors (smoking habits and alcohol consumption). CONCLUSIONS: Patients with higher levels of itch and scratching need more irradiation sessions to achieve clearance of psoriasis with UVB phototherapy. Systematic assessment of the severity of itch and scratching, followed by short-term itch-coping programmes for patients at risk, might be a cost-effective, adjunct to UVB therapy.

Narrowband ultraviolet B therapy in psoriasis: randomized double-blind comparison of high-dose and low-dose irradiation regimens.

BACKGROUND: Ultraviolet (UV) B phototherapy is an established treatment option for psoriasis. The optimum dosage regimen still has to be determined. Within-subject comparisons do not take into account the systemic effects of UVB phototherapy. The area of the body treated with low-dose UVB may benefit from the systemic effects of the site treated with a higher UVB dose. OBJECTIVES: To study the time to clearance in patients with psoriasis in a randomized controlled trial, in which patients were treated with narrowband UVB in either a high-dose or a low-dose regimen. METHODS: One hundred and nine patients were randomized to a high-dose regimen (group 1) or to a low-dose regimen (group 2). Patients of group 1 and 2 were irradiated with 40% and with 20% incremental doses, respectively, three times weekly. Psoriasis Area and Severity Index (PASI) was measured at baseline and at every 4-week control visit. Treatment was stopped in cases of clearance (90% reduction of baseline PASI). RESULTS: No significant differences were found in the number of patients achieving clearance. The high-dosage scheme resulted in four fewer treatments with no significant differences in cumulative UV dose, although more protocol adjustments were required in the beginning of the study because of erythema. After 3 months a significantly better clinical outcome was seen after high-dose UVB therapy. CONCLUSIONS: High-dose UVB therapy results in fewer treatments with better long-term efficacy, with cost-effective benefits for hospital and patients. Therefore UVB phototherapy in a high-dose regimen for psoriasis is recommended. However, a protocol adjustment in the second week with a high-dose regimen is desirable to prevent erythema.

Pretreatment to enhance protoporphyrin IX accumulation in photodynamic therapy.

The response rates of photodynamic therapy (PDT) vary widely. Limited uptake of topically applied 5-aminolaevulinic acid (ALA), or its methyl ester (MAL), and suboptimal production of protoporphyrin IX (PpIX) may account for these differences. Recently, we demonstrated that hyperkeratosis is an important negative factor in ALA uptake. This review has its focus on pretreatment of the skin in order to improve the clinical outcome of ALA/MAL PDT. Pretreatment of hyperkeratosis can be achieved with keratolytics, curettage/debulking, tape stripping, microdermabrasion or laser ablation. Penetration enhancers may alter the composition or organization of the intercellular lipids of the stratum corneum. Several studies have been performed on the use of dimethyl sulfoxide, azone, glycolic acid, oleic acid and iontophoresis to increase the penetration of ALA. As PpIX production is also dominated by temperature-dependent processes, elevating skin temperature during ALA application may also improve treatment results. Another approach is the use of additives that interact with the heme biosynthetic pathway, e.g. by removing ferrous iron with iron-chelating substances such as: ethylenediaminetetraacetic acid; 3-hydroxypyridin-4-ones; 1,2-diethyl-3-hydroxypyridin-4-one-hydrochloride; and desferrioxamine. In conclusion, simple pretreatments or additions to the regular practice of PDT, aimed to optimize intralesional PpIX content, improve the clinical outcome.

A placebo-controlled randomized study on the clinical effectiveness, immunohistochemical changes and protoporphyrin IX accumulation in fractionated 5-aminolaevulinic acid-photodynamic therapy in patients with psoriasis.

BACKGROUND: Topical 5-aminolaevulinic acid (ALA)-photodynamic therapy (PDT) for the treatment of psoriasis has been evaluated in a few studies. In these studies different treatment parameters were used, there was a variable clinical response, and a nonhomogeneous fluorescence was seen after irradiation with Wood's light. OBJECTIVES: To study the clinical effectiveness, immunohistochemical changes and protoporphyrin IX accumulation in ALA-PDT in patients with psoriasis. Eight patients with stable plaque psoriasis with symmetrical involvement were included in the study. Two symmetrical plaques were randomly allocated to PDT either with 10% ALA or with placebo. Irradiation consisted of 2 and 8 J cm(-2) with a dark interval of 2 h (Waldmann PDT 1200 L, 600-750 nm, 40 mW cm(-2)) once weekly for 4 weeks. Before, during and after irradiation, fluorescence diagnosis was performed. Biopsies were taken at baseline, week 1 and week 6 for immunohistochemical assessment. Psoriatic plaques were clinically assessed using the plaque severity (sum) score. Fluorescence diagnosis was performed and expression of immunohistochemical markers for proliferation, differentiation and T-cell infiltration [Ki67, keratin 10 (K10), CD4, CD8 and CD45RO] was assessed. RESULTS: From week 1 up to week 6, ALA-PDT gave a significant reduction in the number of Ki67+ nuclei, while the K10 expression increased. After 6 weeks significant improvement was observed for CD8 and CD45RO. These changes were absent in the placebo-treated lesions. The sum scores were also significantly lower in the ALA-treated plaques. Heterogeneity of macroscopic fluorescence was observed during treatment despite keratolytic treatment. CONCLUSIONS: The present study shows that clinical improvement during fractionated ALA-PDT in psoriasis parallels histological improvement as seen in normalization of epidermal proliferation, differentiation and infiltration of relevant T-cell subsets. Optimizing the current treatment protocol may increase clinical efficacy further.

Heterogeneity of fluorescence in psoriasis after application of 5-aminolaevulinic acid: an immunohistochemical study.

BACKGROUND: Psoriasis has been shown to highly accumulate protoporphyrin IX (PpIX), but a variable distribution within plaques after fluorescence diagnosis is seen. It is unknown what causes this heterogeneity of fluorescence in psoriatic skin, despite adequate keratolytic treatment. Variations in fluorescence might explain the variable and the mostly partial clinical response of psoriasis seen after photodynamic therapy (PDT). OBJECTIVES: This study examines morphological and immunohistochemical differences in inhomogeneous PpIX-induced fluorescence in stable plaque psoriasis. MATERIALS AND METHODS: Fourteen patients with stable plaque psoriasis were included in this study. In each patient one psoriatic plaque was incubated with 20% 5-aminolaevulinic acid (ALA) ointment for 3 h after keratolytic treatment. Fluorescence diagnosis with ALA-induced porphyrins (FDAP) was performed and subsequently high- and low-fluorescent psoriatic skin samples were biopsied. Biopsies were investigated with respect to histological hyperkeratosis (thickness of stratum corneum), proliferation (Ki-67 antigen), keratinization (K10, filaggrin) and inflammation (CD3). Digital images acquired with FDAP were analysed using image analysis software. RESULTS: Inhomogeneous fluorescence was seen in 12 of the 14 plaques. A significantly thicker stratum corneum was found in low-fluorescent psoriatic skin compared with highly fluorescent skin. Fluorescence intensity and thickness of the stratum corneum proved to be negatively correlated. The variable-fluorescent parts of the lesional psoriatic skin showed no differences in epidermal proliferation, keratinization or inflammation. CONCLUSIONS: Heterogeneous ALA-induced fluorescence in psoriasis plaques related to inhomogeneous distribution of PpIX in the epidermis may result from differences in penetration of ALA and/or light within a plaque caused by differences in stratum corneum thickness. The variable clinical response seen after PDT in psoriasis could be explained by this. These findings are consistent with the general assumption that optimal desquamation prior to FDAP or PDT is required for the most favourable results.