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.

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.

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.

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.

[A painful swelling of the tongue]. / Een pijnlijke zwelling van de tong.

A 45-year-old patient had a progressive ulcer of the tongue. Routine examination, including a biopsy was not conclusive and could not entirely rule out a malignancy. The final diagnosis was made after generalised lesions developed, after which specific serological tests confirmed the diagnosis 'syphilis'. The patient was treated with benzathine benzylpenicillin and his complaints disappeared. In view of the increasing incidence of this disease remains an important consideration in case of ulcerative or other lesions in the oral cavity.

[A painful swelling of the tongue]. / Een pijnlijke zwelling van de tong.

A 45-year-old patient had a progressive ulcer of the tongue. Routine examination, including a biopsy was not conclusive and could not entirely rule out a malignancy. The final diagnosis was made after generalised lesions developed, after which specific serological tests confirmed the diagnosis 'syphilis'. The patient was treated with benzathinbenzylpenicillin and his complaints disappeared. In view of the increasing incidence of syphilis this disease remains an important consideration in case of ulcerative or other lesions in the oral cavity.

Vitiligo. Pathogenesis and treatment.

Vitiligo is an acquired skin disorder caused by the disappearance of pigment cells from the epidermis that gives rise to well defined white patches which are often symmetrically distributed. The lack of melanin pigment makes the lesional skin more sensitive to sunburn. Vitiligo can be cosmetically disfiguring and it is a stigmatizing condition, leading to serious psychologic problems in daily life. It occurs worldwide in about 0.5% of the population and it occurs as frequently in males as it does in females. The cause is unknown, but might involve genetic factors, autoimmunity, neurologic factors, toxic metabolites, and lack of melanocyte growth factors. Since a causative (gene) treatment is not (yet) available, current modalities are directed towards stopping progression and to achieving repigmentation in order to repair the morphology and functional deficiencies of the depigmented skin areas. Many treatments have been used for some time; however; there are some new developments: narrowband ultraviolet (UV) B (311 nm) therapy, the combination of corticosteroid cream + UVA therapy, and the transplantation of autologous pigment cells in various modalities. In widespread vitiligo, residual pigment can be removed by depigmentation agents. Sunscreens, camouflage products, and good guidance may help the patient cope better with the disease.

Depigmentation therapy in vitiligo universalis with topical 4-methoxyphenol and the Q-switched ruby laser.

BACKGROUND: Monobenzylether of hydroquinone is used worldwide to remove residual pigment in patients with vitiligo universalis. Because of the side effects reported with this drug, the use of monobenzylether of hydroquinone has been restricted in The Netherlands. OBJECTIVE: Our purpose was to evaluate the long-term effectiveness and safety of a combination therapy consisting of topical 4-methoxyphenol (4-MP) cream and Q-switched ruby (QSR) laser in 16 patients with vitiligo universalis. METHODS: In a retrospective study, patient record forms were evaluated. Data were collected regarding history as well as physical and histologic examination. The patients came to the institute for a follow-up visit after a treatment-free period of 2 to 36 months. RESULTS: Thirteen patients received both therapies. Three patients only used the cream. None of the areas was treated by the cream and QSR laser at the same time. In 11 of the 16 patients (69%; 95% confidence interval [CI], 41%-89%) total depigmentation was achieved using the 4-MP cream. Onset of depigmentation was between 4 and 12 months. Four of the 5 patients who did not respond to the 4-MP cream had successful depigmentation with the QSR laser. Mild burning or itching was reported with the cream in 4 cases (25%). Of the 11 patients who responded to the 4-MP cream, 4 had recurrence of pigmentation (relapse rate of 36%; 95% CI, 11%-69%) after a treatment-free period of 2 to 36 months. In 9 of the 13 patients (69%; 95% CI, 39%-91%) total depigmentation was achieved after QSR laser therapy. Onset of depigmentation was between 7 and 14 days after the treatment. Three of the 4 unresponsive patients showed total depigmentation after application of the 4-MP cream. No side effects were observed. Of the 9 patients who responded to QSR laser therapy, 4 had recurrence of pigmentation (relapse rate of 44%; 95% CI, 14%-79%) after a treatment-free period of 2 to 18 months. These patients had a negative Koebner phenomenon. CONCLUSION: Depigmentation therapy using a 4-MP cream and/or QSR laser therapy is an effective and safe method to remove disfiguring residual pigment in patients with vitiligo universalis. Patients should be warned that repigmentation may occur, even after total depigmentation has been achieved.

Treatment of generalized vitiligo in children with narrow-band (TL-01) UVB radiation therapy.

BACKGROUND: Only a few clinical trials have been performed on the treatment of generalized vitiligo in children. Recently, narrow-band UVB therapy has been reported to be an effective and safe therapeutic option in adult patients with vitiligo. OBJECTIVE: We studied the efficacy and safety of UVB (311 nm) therapy in children with generalized vitiligo and evaluated the effect of the therapy on the quality of life in these children. METHODS: In an open trial, 51 children (20 males, 31 females) with generalized vitiligo were treated twice weekly with narrow-band UVB radiation therapy for the maximum period of 1 year. The Children's Dermatology Life Quality Index (CDLQI) was used to evaluate the psychosocial impact of disease and treatment and was scored before and after therapy. RESULTS: The treatment resulted in more than 75% overall repigmentation in 53% of patients and in stabilization of the disease in 80%. Responsiveness to therapy was positively correlated with localization of the lesions and the patients' compliance. Adverse events were limited and transient. The better the repigmentation grade, the better the CDLQI scores had improved. CONCLUSION: Narrow-band UVB therapy is effective and safe in childhood vitiligo; it also may significantly improve the quality of life.

The development of guidelines for the treatment of vitiligo. Clinical Epidemiology Unit of the Istituto Dermopatico dell'Immacolata-Istituto di Recovero e Cura a Carattere Scientifico (IDI-IRCCS) and the Archives of Dermatology.

OBJECTIVE: To develop and introduce evidence-based guidelines for the treatment of vitiligo in children and in adults. PATIENTS AND SETTING: Patients, residents, and dermatologists from the Department of Dermatology, Academic Medical Center, University of Amsterdam, and the Netherlands Institute for Pigmentary Disorders in Amsterdam. DESIGN: Scientific evidence obtained from 3 systematic reviews of the literature was combined with the results of 2 questionnaires and interviews of potential users of the guidelines, 3 internal expert meetings, and 1 local expert meeting, during which preliminary guidelines were presented and commented on. A final version of the guidelines was synthesized and disseminated among potential users. Six months after the introduction of these guidelines, their use was evaluated. RESULTS: Before the development of the guidelines, there was no uniformity in treatment selection, and there was a variability in estimates of treatment outcome. The metaanalysis showed class 3 corticosteroids and narrowband UV-B to be the most effective and safest therapies for localized and for generalized vitiligo, respectively. From another systematic review, it could be concluded that patients with segmental, stable, or lip-tip vitiligo could be successfully treated with most autologous transplantation methods. For vitiligo universalis, results of the systematic review showed that depigmentation using monobenzone or a Q-switched ruby laser was equally effective. The final version of the guidelines consisted of a treatment scheme together with detailed treatment protocols. Implementation of the guidelines was evaluated in 5 physicians. After the introduction of these guidelines, they were followed in most adult cases with vitiligo (71% of patients with localized vitiligo, 82% with generalized vitiligo, 100% with stable or segmental vitiligo, and 80% with universal vitiligo). In children with vitiligo, the physicians adhered to the guidelines for 52% of the cases. CONCLUSIONS: Guidelines for the treatment of vitiligo can be successfully developed and disseminated for daily clinical practice. The results of the implementation of these guidelines should be confirmed in other centers involving more clinicians.

Management of vitiligo. Results of a questionnaire among dermatologists in The Netherlands.

BACKGROUND: Several therapeutic options are available for the treatment of vitiligo. Concern exists that there is no uniform approach towards the management of vitiligo among Dutch dermatologists. METHODS: A written survey concerning the management of vitiligo was sent to 332 dermatologists in The Netherlands. RESULTS: The response rate was 86%. "Giving information and reassurance concerning the nature of disease" was regarded by most dermatologists (68%) as being the most important goal in the management of vitiligo. Only 16% of the dermatologists aimed for active treatment in vitiligo. The reported therapy choices in children resembled those of adults, except that slightly more dermatologists did not prescribe active therapy in children. Nine different therapeutic modalities were mentioned as first choice therapies. Topical corticosteroids were indicated by most dermatologists as first choice therapy (241 out of 266, i.e. 91%); however, only 2% indicated that 50% or more of the patients achieved a successful treatment; 66% found that less than 25% of the patients were successfully treated with topical corticosteroids. Only 15% of the respondents reported that 50% or more of the patients were treated successfully with narrow-band UVB. The observed response profile to broad-band UVB therapy was found to be comparable with that of narrow-band UVB. The classical therapy with oral psoralen plus UVA (PUVA) was prescribed as first choice therapy by only 12% (32 out of 266) of the dermatologists. Only 6% of these respondents observed that 50% or more of the patients achieved successful therapy using oral PUVA. The recommended maximum treatment duration for topical corticosteroids, oral PUVA, and UVB therapy was found to vary from 3 to 12 months. CONCLUSIONS: Most dermatologists in The Netherlands do not offer active treatment in vitiligo, probably because the estimated effectiveness of (nonsurgical) repigmentation therapy is low. In cases where treatment is prescribed, there appears to be no consensus on the choice of therapies and treatment strategies. The development of practice guidelines may be helpful in reducing inappropriate care and improving treatment outcome.

Association of the Köbner phenomenon with disease activity and therapeutic responsiveness in vitiligo vulgaris.

OBJECTIVE: To investigate the association between the experimentally induced Kobner phenomenon (KP-e) and the Kobner phenomenon by history (KP-h), disease activity, and therapeutic responsiveness in vitiligo vulgaris. DESIGN: Cohort study. SETTING: An outpatient clinic. PATIENTS: Sixty-one consecutive patients with vitiligo vulgaris. INTERVENTION: Three months after a standardized epidermodermal injury was induced, the KP-e was evaluated. For 1 year, UV-B (311 nm) therapy or topical fluticasone propionate plus UV-A therapy was given, depending on the severity of depigmentation. MAIN OUTCOME MEASURES: The presence or absence of the KP-e and the KP-h disease activity as scored on a 6-point scale from -1 to +4 (vitiligo disease activity [VIDA] score) and therapy-induced repigmentation grade. RESULTS: Nineteen (31%) of the patients had a positive KP-h, whereas 37 (61%) showed a positive KP-e (P<.001). The VIDA score did not always predict a positive KP-e, although patients with a positive KP-e had a higher mean VIDA score (VIDA score of 1.6) than did patients with a negative KP-e (VIDA score of 0.5) (P<.001). The responsiveness to UV-B (311 nm) therapy among KP-e-positive or KP-e-negative patients was not significantly different (P=.66). However, KP-e-positive patients who were treated with fluticasone propionate plus UV-A showed a better response than did KP-e-negative patients (P=.01). Among patients responding to both therapies, VIDA scores were significantly decreased (P<.001) compared with VIDA scores before therapy. CONCLUSION: The KP-e may function well as a clinical factor to assess present disease activity and may also predict the responsiveness to fluticasone propionate plus UV-A therapy but not to UV-B (311 nm) therapy.

Nonsurgical repigmentation therapies in vitiligo. Meta-analysis of the literature.

OBJECTIVE: To assess the effectiveness and safety of nonsurgical repigmentation therapies in localized and generalized vitiligo by means of a meta-analysis. DATA SOURCES: Computerized searches of bibliographic databases, a complementary manual literature search, and contacts with researchers and pharmaceutical firms. STUDY SELECTION: Predefined selection criteria were applied to both randomized and nonrandomized controlled trials. DATA EXTRACTION: Two investigators independently assessed the articles for inclusion. When there was a disagreement, a third investigator was consulted. DATA SYNTHESIS: Sixty-three studies were found on therapies for localized vitiligo. Of these, 10 of 11 randomized controlled trials and 29 of 110 patient series were included. One hundred seventeen studies on therapies for generalized vitiligo were found. Of these, 10 of 22 randomized controlled trials and 46 of 231 patient series were included. Among randomized controlled trials on localized vitiligo, the pooled odds ratio vs placebo was significant for topical class 3 corticosteroids (14.32; 95% confidence interval [CI], 2.45-83.72). In the patient series, topical class 3 and class 4 corticosteroids carried the highest mean success rates (56% [95% CI, 50%-62%] and 55% [95% CI, 49%-61%], respectively). Side effects were reported mostly with topical psoralen and intralesional and class 4 corticosteroids. In the randomized controlled trials on generalized vitiligo, the odds ratio vs placebo was significant for oral methoxsalen plus sunlight (23.37; 95% CI, 1.33-409.93), oral psoralen plus sunlight (19.87; 95% CI, 2.37-166.32), and oral trioxsalen plus sunlight (3.75; 95% CI, 1.24-11.29). In the series, the highest mean success rates were achieved with narrowband UV-B (63%; 95% CI, 50%-76%), broadband UV-B (57%; 95% CI, 29%-82%), and oral methoxsalen plus UV-A therapy (51%; 95% CI, 46%-56%). Oral methoxsalen plus UV-A was associated with the highest rates of side effects. No side effects were reported with UV-B therapy. CONCLUSIONS: Class 3 corticosteroids and UV-B therapy are the most effective and safest therapies for localized and for generalized vitiligo, respectively.

A systematic review of autologous transplantation methods in vitiligo.

OBJECTIVE: A systematic review of the effectiveness, safety, and applicability of autologous transplantation methods in vitiligo. DATA SOURCES: Computerized searches of bibliographical databases, a complementary manual literature search, and contacts with researchers and pharmaceutical firms. STUDY SELECTION: Predefined selection criteria were applied to all studies found. DATA EXTRACTION: Two investigators independently assessed the articles for inclusion. When there was a disagreement, a third investigator was consulted. DATA SYNTHESIS: Sixty-three studies were found, of which 16 reported on minigrafting, 13 on split-thickness grafting, 15 on grafting of epidermal blisters, 17 on grafting of cultured melanocytes, and 2 on grafting of noncultured epidermal suspension. Of these, 39 patient series were included. The highest mean success rates (87%) were achieved with split-skin grafting (95% confidence interval, 82%-91%), and epidermal blister grafting (87%) (95% confidence interval, 83%-90%). The mean success rate of 5 culturing techniques varied from 13% to 53%. However, in 4 of the 5 culturing methods, fewer than 20 patients were studied. Minigrafting had the highest rates of adverse effects but was the easiest, fastest, and least expensive method. CONCLUSIONS: Because no controlled trials were included, treatment recommendations should be formulated with caution. Split-thickness and epidermal blister grafting can be recommended as the most effective and safest techniques. No definite conclusions can be drawn about the effectiveness of culturing techniques because only a small number of patients have been studied. The choice of method also depends on certain disease characteristics and the availability of specialized personnel and equipment.