Etanercept plus narrowband ultraviolet B phototherapy of psoriasis is more effective than etanercept monotherapy at 6 weeks

Background A substantial portion of patients with psoriasis does not achieve a satisfactory response under antitumour necrosis factor (TNF)‐α biological therapies. Objectives We aimed to evaluate whether etanercept plus narrowband ultraviolet B (NB‐UVB) phototherapy is superior to etanercept monotherapy in the management of psoriasis. Methods In this prospective study, patients with psoriasis were treated with etanercept 25 mg twice weekly. Two marker lesions were selected for determination of the modified Psoriasis Area and Severity Index (M‐PASI). NB‐UVB was administered thrice weekly whereby one marker lesion was covered as nonirradiated control. Skin biopsies for histology and immunohistochemistry were performed in both marker lesions after a 6‐week treatment course. Results After 6 weeks of therapy, the relative M‐PASI reduction (mean ± SD) in etanercept‐treated sites (53·7 ± 36·9%) was significantly lower than the reduction in etanercept plus NB‐UVB‐treated lesions (64 ± 27·8%; P = 0·011). At the end of treatment, histology scores of etanercept‐treated psoriatic plaques were significantly higher than scores of etanercept plus NB‐UVB‐treated sites (4·6 ± 2·7 vs. 3·7 ± 2·4; P = 0·045). Epidermal immunoreactivity for CD1a, CD4 and CD8 was significantly lower in etanercept plus NB‐UVB‐treated lesions when compared with etanercept monotherapy. Conclusions Etanercept combined with NB‐UVB is more effective than etanercept monotherapy at 6 weeks as demonstrated at a clinical, histological and immunohistological level. However, as there is an increased risk for malignancy by treatment with TNF‐α blockers alone or in combination with phototherapy, we recommend to restrict this highly effective combination to short periods of time, for instance to obtain a quicker response, and to avoid long‐term treatment.     

Efficacy and safety of systemic methotrexate vs. acitretin in psoriasis patients with significant palmoplantar involvement: a prospective,randomized study

Background Palmoplantar psoriasis (PP) is a chronic, inflammatory and proliferative dermatosis of the palms and/or soles with significant morbidity. It is notoriously difficult to treat and unresponsive to traditional topical agents. Material and methods This was a prospective, randomized study involving 111 patients of psoriasis with significant palmoplantar disease. Patients meeting the eligibility criteria were randomly assigned to one of the two treatment groups. Patients in Group I received methotrexate in doses of 0.4 mg/kg weekly, and patients in Group II received acitretin in doses of 0.5 mg/kg daily. Patients were evaluated by modified PPPASI (m‐PPPASI) score for palm and sole involvement at baseline, at two weekly intervals for the first 4 weeks and then four weekly for next 8 weeks. Treatment protocol was continued for a period till patient achieved 75% reduction in m‐PPPASI from baseline or 12 weeks whichever was earlier. Results There was a statistically significant difference in reduction of m‐PPPASI of patients on methotrexate at weeks 8 and 12. The mean m‐PPPASI at week 8 was 15.38 ± 6.08 in methotrexate group and 17.23 ± 5.25 in acitretin group (P = 0.04). The mean m‐PPPASI at week 12 was 10.30 ± 5.97 in methotrexate group and 12.40 ± 5.31 in acitretin group (P = 0.03). Marked improvement (m‐PPPASI 75) was achieved in 12 (24%) patients in methotrexate group compared with 4 (8%) in acitretin group which was statistically significant (P = 0.029). Adverse events were generally mild and were seen in 14 patients in methotrexate group and 15 patients in acitretin group (P = 0.080). Conclusion Methotrexate is relatively inexpensive, safe and efficacious drug for the treatment of psoriasis patients with significant palmoplantar involvement. Acitretin can be used as an alternative therapy and with a good safety profile.     

Comparison of narrowband ultraviolet B exposure and oral vitamin D substitution on serum 25-hydroxyvitamin D concentration

Summary Background A short course of narrowband ultraviolet B (NB‐UVB) exposures increases the serum 25‐hydroxyvitamin D [25(OH)D] concentration in patients with psoriasis and healthy subjects. Objectives To compare the effects of NB‐UVB and oral vitamin D substitution in healthy subjects in winter. Methods Healthy adult hospital employees and medical students were screened for serum 25(OH)D concentration. Those with 25(OH)D below 75 nmol L^?1 were randomly given either 12 NB‐UVB exposures or 20 μg of oral cholecalciferol daily for 4 weeks. The NB‐UVB exposures were given with a Waldmann UV 7001 cabin and the mean cumulative dose was 48·4 standard erythema doses. Serum 25(OH)D was measured before and after the treatments by radioimmunoassay. Results The baseline serum 25(OH)D concentrations were 52·9 ± 10·4 (mean ± SD) in the 33 NB‐UVB‐treated and 53·5 ± 12·7 nmol L^?1 in the 30 oral cholecalciferol‐treated subjects. The mean increase in serum 25(OH)D was 41·0 nmol L^?1 [95% confidence interval (CI) 34·8–47·2; P < 0·001] in the NB‐UVB group and 20·2 nmol L^?1 (95% CI 14·6–26·0; P < 0·001) in the cholecalciferol group. The difference between the two treatments was significant at 2 weeks (P = 0·033) and at 4 weeks (P < 0·001). One month after the treatments the 25(OH)D concentrations had increased further. Conclusions The present study shows that 12 NB‐UVB exposures given during 4 weeks increase serum 25(OH)D concentration significantly more than 20 μg of oral cholecalciferol daily. A short NB‐UVB course is an effective way to improve vitamin D balance in winter and the response is still evident 2 months after the course.     

Narrowband ultraviolet B phototherapy for patients with refractory uraemic pruritus: a randomized controlled trial

Background Pruritus is very common in uraemic patients, but the treatment remains challenging. Studies regarding narrowband ultraviolet B (NB‐UVB) phototherapy for uraemic pruritus are rare. Objectives To investigate whether or not NB‐UVB phototherapy is an effective treatment for uraemic pruritus. Methods We conducted a single‐blind, randomized, controlled trial for patients with refractory uraemic pruritus. The treatment group received NB‐UVB phototherapy three times per week for 6 weeks. The dose of NB‐UVB started from 210 mJ cm^?2 and was increased by 10% each time. The control group received time‐matched exposures to long‐wave UVA radiation. A visual analogue scale (VAS) score was evaluated weekly for pruritus intensity for 12 weeks. The characteristics of pruritus were also assessed by a questionnaire at baseline and after 6 weeks of phototherapy. Results Both the NB‐UVB and control groups had significant and comparable improvement in the pruritus intensity VAS scores during the period of phototherapy and follow‐up. Compared with the control group, the NB‐UVB group showed a significant improvement in the involved body surface area affected by pruritus (P = 0·006), but not in sleep quality. More detailed regression and estimating analysis revealed that the patients in the NB‐UVB group had lower pruritus intensity scores at week 6, week 10 and week 12. This may indicate a beneficial difference at certain time points, but the effect seems marginal. Conclusions NB‐UVB phototherapy does not show a significant effect in reducing pruritus intensity compared with a control group for refractory uraemic pruritus. Further studies are warranted.     

A randomized, ‘head‐to‐head’ pilot study comparing the effects of etanercept monotherapy vs. etanercept and narrowband ultraviolet B (NB‐UVB) phototherapy in obese psoriasis patients

Background Etanercept is a tumour necrosis factor‐alpha antagonist used for the treatment of moderate‐to‐severe psoriasis. Current opinion suggests that etanercept may have reduced efficacy in obese patients. Narrowband ultraviolet B (NB‐UVB) phototherapy is unaffected by body weight and the addition of NB‐UVB to etanercept therapy may supplement the efficacy of etanercept in these patients. Objective To evaluate the efficacy and safety of NB‐UVB phototherapy when administered in conjunction with 50 mg of etanercept once weekly in the treatment of obese patients with moderate‐to‐severe plaque psoriasis. Methods Thirty psoriasis patients with a body mass index (BMI) greater than 30 were enrolled into this randomized, ‘head‐to‐head’ comparison study. All subjects received 50 mg of etanercept twice weekly for 12 weeks and then randomized to receive either etanercept monotherapy or combination etanercept and NB‐UVB three times weekly for an additional 12 weeks. Treatment response was evaluated using Psoriasis Area and Severity Index (PASI), body surface area (BSA) and Physician’s Global Assessment (PGA) scores. Results Twenty‐five subjects completed the study. At 12 weeks, 48% of all patients achieved PASI 75. By Week 24, 62.5% of all patients achieved PASI 75. Patients in the etanercept monotherapy and combination etanercept and NB‐UVB phototherapy arms had similar rates of achieving PASI 75 (46.7% vs. 53.3% of each group, respectively). Conclusion Combination etanercept and NB‐UVB has similar efficacy to etanercept monotherapy in obese patients. This result indicates that even in the setting of obesity, the majority of patients respond well to etanercept, with or without NB‐UVB.     

Efficacy and safety of systemic methotrexate in two fixed doses of 10 mg or 25 mg orally once weekly in adult patients with severe plaque-type psoriasis: a prospective, randomized, double-blind, dose-ranging study

Background. Methotrexate (MTX) is the ‘gold‐standard’ drug for the treatment of severe psoriasis. In the absence of any consensus on an optimum dose of MTX for psoriasis, there is wide variation in prescribing patterns between dermatologists, resulting in variable or delayed therapeutic effects. Aim. To identify the most effective fixed single weekly dose of oral MTX with acceptable side‐effects in the treatment of severe plaque‐type psoriasis. Methods. This was a prospective, randomized, double‐blind, parallel‐group, dose‐ranging study, which enrolled 60 patients of both genders (aged 18–62 years) with severe chronic plaque‐type psoriasis. Patients were randomly assigned to one of two groups: group A was treated with MTX 10 mg once weekly, and group B was treated with 25 mg MTX once weekly. The main outcome measure was change in Psoriasis Area and Severity Index (PASI) between the two groups from baseline to 12 weeks. Results. Of the 60 patients, 51 (85%) completed the 12‐week study. At the end of the study, 24 patients (92.3%) in the MTX 25 mg group had achieved a 75% reduction in PASI (PASI 75) from baseline, compared with 18 patients (72%) in the MTX 10 mg group (P > 0.05). Mean time in weeks to achieve PASI 75 was significantly shorter in the MTX 25 mg group (7.92 ± 1.91) than in the MTX 10 mg group (9.47 ± 2.29) (P < 0.05). In addition, 20 patients (69%) in the MTX 25 mg group achieved 100% reduction in PASI compared with 9 patients (30%) in the MTX 10 mg group within 12 weeks of the study period (P < 0.01). Adverse effects were generally mild, and were noted in 43.1% of the 51 patients who completed the study, with no significant difference in frequency between the two groups, although they were less severe in the 10 mg group. Conclusions. MTX 25 mg is an effective dose as monotherapy for the treatment of severe psoriasis, whereas the 10 mg dose is slow to act and less effective, but has a less severe side‐effect profile.     

Subcutaneous methotrexate versus oral form for the treatment and prophylaxis of chronic plaque psoriasis

Psoriasis is a common inflammatory skin disorder with complex pathomechanisms. Methotrexate (MTX) is an antiproliferative and immunomodulating agent that control psoriasis. The aim of this study is to compare the efficacy of MTX and tolerability to MTX by oral route versus subcutaneous (SC) route. Twenty‐eight cases were divided into two equal groups: Group I received a weekly dose of oral MTX and Group II received a weekly dose of SC MTX for 12 weeks. The starting dose was 7.5–10 mg and increased gradually by 2.5 mg every month till reaching 12.5–15 mg/week. Patients' clinical responses were evaluated according to Psoriasis Area and Severity Index (PASI) score. Results suggest that Group I patients showed reduction in PASI score of mean ± SD from 19 ± 7.4 before treatment to 11.2 ± 6.29 after treatment while Group II patients showed reduction from 23.4 ± 14.7 before treatment to 2.55 ± 2.6 after treatment with highly statistically significant difference between both groups. Clinical improvement was complete in 7.1% of Group I versus 57.1% of Group II. In conclusion, SC MTX has higher efficacy with lesser adverse effects and lower relapse rate when compared to oral form given by the same dose during the same duration.     

Safety and efficacy profile of oral cyclosporine vs oral methotrexate vs oral acitretin in palmoplantar psoriasis: A hospital based prospective investigator blind randomized controlled comparative study

Palmoplantar psoriasis (PPP) is a variant of psoriasis which affects only 5% body surface area, but has a devastating impact on affected individual's quality of life. There are few studies assessing efficacy of individual drugs, and few comparative studies of efficacy of two drugs in the literature, however randomized control trial comparing all three drugs against each other has not been done. A total of 75 patients of PPP were enrolled for study and randomly divided into three groups A, B, C of 25 each and assigned for treatment with cyclosporine (CSA) (2.5‐5 mg/kg/d), methotrexate (MTX)(7.5‐15 mg/week), and acitretin (ACT) (25‐50 mg/d), respectively. Modified psoriasis area and severity index (PASI), psoriasis severity scale, visual analogue scale, physician global assessment, and PPQOL were used for monitoring response to therapy and improvement in quality of life up to end of study, and thereafter monthly follow‐up was done to find duration of remission for next 90 days. Side effects if any were recorded. There was a statistically significant difference in modified PASI for CSA, MTX, and ACT. The mean modified PASI at baseline was 12.8 ± 4.8 for CSA, 12.57 ± 3.8 for MTX, and 11.92 ± 3.28 for ACT (P = .75). Mean modified PASI reduced to 2.91 ± 1.8 for CSA, 6.57 ± 2.2 for MTX, and 4.7 ± 2.2 for ACT at week 5 (P = <.01). Mean modified PASI further reduced to 0.095 ± 0.35 for CSA, 2.12 ± 1.4 for MTX, and 0.78 ± 0.97 for ACT at end of study (P = <.01). However, average duration of remission was 9 weeks for ACT group, followed by 6.47 and 3 weeks for CSA and MTX group, respectively. Adverse events were comparatively more in ACT group as compared to MTX and CSA groups. PPP affects quality of life tremendously and warrants systemic treatment for the same. CSA provides fastest resolution of lesions and have highest efficacy. MTX and ACT have similar efficacy, but ACT provides longer duration of remission.     

Evaluation of the effect of narrow band‐ultraviolet B on the expression of tyrosinase,TYRP‐1, and TYRP‐2 mRNA in vitiligo skin and their correlations with clinical improvement: A retrospective study

Narrowband‐ultraviolet B (NB‐UVB) is considered one of the main therapeutic tools in vitiligo, which is able to induce repigmentation and halt depigmentation. However, little remains known about the effect of NB‐UVB on TYR gene family, the main pigmentary genes, in vitiligo patients. To assess the effect of NB‐UVB on expression of some genes related to the pigmentary problem of vitiligo; tyrosinase (TYR), tyrosinase related protein 1 (TYRP1) and tyrosinase related protein 2 (TYRP2), mRNA levels of those genes were quantitatively evaluated by Real‐Time quantitative Polymerase Chain Reaction (RT‐qPCR) in skin biopsies obtained from 30 patients with nonsegmental vitiligo and five healthy controls. Vitiligo patients were classified into two groups; group 1, involving 12 untreated vitiligo patients and group 2, including 18 vitiligo patients treated by NB‐UVB. The levels of TYR, TYRP‐1, and TYRP‐2 mRNAs in untreated group were significantly lower than in control subjects (P < .001). In NB‐UVB treated group, the three genes were significantly higher than in group 1 (P < .001), however, they were still significantly lower than in the control subjects (P < .001). A significant positive correlation was detected between TYR and TYRP‐2 genes in group 2 (P = .03). This study demonstrated that mRNA level of TYR, TYRP‐1, and TYRP‐2, which decreased in vitiligo, was significantly increased upon treatment with NB‐UVB. Accordingly, the mechanism of depigmentation in vitiligo disease and repigmentation by NB‐UVB treatment may be related to the changes in the expression of these genes.     

Randomized clinical trial of combined therapy with oral α‐lipoic acid and NB‐UVB for nonsegmental stable vitiligo

Vitiligo is associated with oxidant stress and α‐lipoic acid (ALA) is an antioxidative agent. To evaluate the efficacy and safety of oral ALA in combination with NB‐UVB phototherapy on nonsegmental stable vitiligo. The prospective, multi‐center, parallel controlled, double‐blind randomized clinical trial was conducted from 2012 to 2014, in seven comprehensive tertiary hospitals in China. The patients were randomized into oral ALA group or placebo group at a dose of 300 mg daily for 6 months. All of them received NB‐UVB phototherapy three times weekly. The repigmentation rate was evaluated by 4‐point grading scale of improvement: >98%, 50‐98%, 10‐49%, <10%. A total of 133 patients were enrolled in the study, including 72 cases in treatment group and 61 cases in control group. In treatment group, 2.04% (1/49) patients achieved ≥50% improvement at 1‐month after enrollment (M1), and the percentage of patients increased to 8.51% (4/47), 14.0% (6/43), and 37.8% (14/37) at M2, M3, and M6, respectively. In control group, the percentages were similar at all timepoints. No significant difference was seen between the two groups (P > .05). For elder patients, younger patients, male or female, no significant differences were found between treatment group and control group at all timepoints. ALA did not show additional benefit to NB‐UVB therapy in the treatment of nonsegmental stable vitiligo. More studies should be done to identify other protocols of ALA or other types of antioxidants for stable vitiligo.     

Medium-dose ultraviolet (UV) A1 vs. narrowband UVB phototherapy in atopic eczema: a randomized crossover study

Background Ultraviolet (UV) A1 and narrowband (NB)‐UVB have been reported to be effective treatments for atopic eczema (AE). Objectives We aimed to compare the efficacy of medium‐dose UVA1 and NB‐UVB mono‐phototherapy in patients with AE. Methods A randomized double‐blind controlled crossover trial (ClinicalTrials.gov Identifier: NCT00419406) was conducted in which patients with AE received a 6‐week course of both medium‐dose UVA1 and NB‐UVB. Clinical efficacy was assessed using the Six Area, Six Sign, Atopic Dermatitis (SASSAD) score and a visual analogue scale for pruritus. Assessment of health‐related quality of life was performed using the Skindex‐29. Total immunoglobulin E (IgE) and eosinophilic cationic protein (ECP) were evaluated at baseline and after each phototherapy course. Results Twenty‐eight patients who completed both UVA1 and NB‐UVB phototherapy courses on an intention‐to‐treat basis were analysed according to the crossover design. Both interventions were associated with significant clinical improvement but there was no significant difference between treatments with respect to the mean ± SD relative reduction (RR) of the clinical scores (SASSAD, 43·7 ± 31·4% vs. 39·4 ± 24·1%, P = 0·5; pruritus score, 16 ± 61·8% vs. 25·2 ± 30·5%, P = 0·5, respectively). There was no significant difference in the mean ± SD RR of the Skindex‐29 after UVA1 and NB‐UVB phototherapy (12·7 ± 18·8% vs. 16·5 ± 17·6%, P = 0·1). Changes in the total IgE and ECP levels following UVA1 and NB‐UVB did not differ significantly (P = 0·3 and P = 0·9, respectively). Conclusions A 6‐week course of NB‐UVB and UVA1 phototherapy of AE resulted in significant clinical improvement. With regard to efficacy and tolerability, both phototherapeutic modalities may be considered comparably good.     

Weekly vs. daily administration of oral methotrexate (MTX) for generalized plaque psoriasis: a randomized controlled clinical trial

Methotrexate (MTX) treatment for psoriasis is most often administered weekly, because the drug has been considered more hepatotoxic when taken daily. However, some patients may tolerate smaller, more frequent doses better. Objective  To study the efficacy and toxicity of daily vs. weekly MTX. Patients and methods  In a randomized controlled trial, 101 patients with generalized plaque psoriasis received oral MTX 2.5 mg daily for 6 days (Group 1), and another 101 patients received oral MTX 15 mg weekly (Group 2) in three divided doses (every 8 hours during a 24‐hour period). Patients were followed monthly for 4 months as research participants, then for 1 year as part of their routine care. Complete blood counts, liver function tests, blood urea nitrogen, serum creatinine, urinalysis, and psoriasis area and severity index (PASI) scores were determined pre‐treatment and at the following intervals after starting treatment: 2 weeks, 4 weeks and monthly for a total of 4 months. Changes in PASI scores were classified into three categories: >75% improvement was considered significant; 25–75% moderate; and <25% poor. Results  Sixty Group 1 patients and 81 Group 2 patients showed a significant response (P‐value 0.001); 19 patients in Group 1 and 14 in Group 2 responded moderately; 22 patients in Group 1 and six patients from Group 2 responded poorly. Forty‐five patients in Group 1 and 33 in Group 2 developed transient increases in liver enzymes (P‐value 0.11). Nausea, headache, fatigue, and gastrointestinal upset were noted in four Group 1 patients and 30 Group 2 patients (P‐value 0.0001). Conclusion  Nausea, vomiting, headache, and fatigue were significantly less common side effects in our patients who received MTX daily, but liver enzyme abnormalities were less common, and clinical efficacy was greater in the patients who received MTX weekly.     

Comparison of clinical effects of psoriasis treatment regimens among calcipotriol alone,narrowband ultraviolet B phototherapy alone,combination of calcipotriol and narrowband ultraviolet B phototherapy once a week,and combination of calcipotriol and narrowband ultraviolet B phototherapy more than twice a week

We compared the clinical efficacy of various psoriasis treatments among: (i) topical application of calcipotriol ointment twice daily (group I); (ii) topical application of calcipotriol ointment twice daily and narrowband ultraviolet B NB‐UVB phototherapy once a week (group II); (iii) topical application of heparinoid ointment twice daily and NB‐UVB phototherapy more than twice a week (group III); and (iv) topical application of calcipotriol ointment twice daily and NB‐UVB phototherapy more than twice a week (group IV). Ten patients were randomly selected for each group and treated by the indicated regimens for 12 weeks. All treatments were effective and significantly improved Psoriasis Area and Severity Index (PASI) scores, self‐administered PASI scores and visual analog scale scores of pruritus. Group IV showed most marked and rapid reduction in PASI and self‐PASI scores among the four regimens. Although the serum levels of interleukin (IL)‐17, IL‐20 and IL‐22 and psoriasis disability index were significantly decreased after the treatments, no significant difference was detected among the four groups. Our study indicates that combination of calcipotriol ointment plus NB‐UVB more than twice a week is superior to other treatment regimens, rapidly improving psoriasis lesions.     

Treatment of palmoplantar psoriasis with infliximab: a randomized,double‐blind placebo‐controlled study

Background Palmoplantar psoriasis is a difficult to treat variant of plaque psoriasis. Objective To study the safety and efficacy of infliximab in non‐pustular palmoplantar psoriasis. Methods Patients with non‐pustular palmoplantar psoriasis affecting at least 10% of their palms and soles and with a modified palmoplantar psoriasis area and severity index (m‐PPPASI) of at least eight were recruited. Patients were randomized (1:1) to receive infliximab 5 mg/kg or placebo at weeks 0, 2 and 6. Patients initially randomized to placebo received infliximab at weeks 14, 16 and 20 whereas patients randomized to infliximab received additional infliximab infusions every 8 weeks until week 22. Results Twenty four (24) patients were randomized in this study. At week 14, 33.3% and 66.7% of patients treated with infliximab achieved m‐PPPASI 75 and m‐PPPASI 50 respectively compared to 8.3% for both m‐PPPASI 75 (P = 0.317) and m‐PPPASI 50 (P = 0.009) for patients randomized to placebo. A reduction of 50.3% in the mean surface area of palms and soles affected with psoriasis was seen at week 14 in patients randomized to infliximab as compared to an increase of 14.9% in patients randomized to placebo (P = 0.009). Conclusions This pilot study did not reach its primary endpoint of m‐PPPASI 75 at week 14. However, infliximab was observed to be more efficacious than placebo in improving PPSA and with respect to the percentage of patients reaching m‐PPPASI 50 at week 14. Larger and longer term studies are needed for severe patients to better assess the efficacy of infliximab in palmoplantar psoriasis.     

Evaluation of narrow band ultraviolet B phototherapy in the treatment of chronic actinic dermatitis in Chinese patients

Few studies have been conducted in chronic actinic dermatitis (CAD) treated with narrowband ultraviolet B (NB UVB) phototherapy, especially in Asian patients. We aim to evaluate the efficacy and safety of NB UVB phototherapy in Chinese patients with CAD. 19 CAD patients of Fitzpatrick skin phototype IV received NB UVB phototherapy in spring and treatments were given 3 times weekly with incremental dose and maintenance therapy was given twice weekly for 3–4 weeks. The mean initial, endpoint, and cumulative dose of NB UVB was 0.08, 0.33, and 6.0 J/cm², respectively. Patients totally received 27 times of treatments in average. 87.5% of previously ultraviolet B（UVB） sensitive patients and 75% of previously ultraviolet A（UVA） sensitive patients had normal or improved MED after phototherapy. The percentage of patients returned to normal UVB phototesting was higher than that of patients returned to normal UVA phototesting (68.8% vs. 37.5%). The mean 1‐week DLQI and the need for using immunosuppressive agents and antihistamines were significantly reduced after treatment (p < .01 or p < .05). In conclusion, prophylactic NB UVB phototherapy is effective and safe in treatment of CAD in Chinese patients with Fitzpatrick skin phototype IV.     

Simultaneous improvement and worsening of vitiligo lesions during the course of NB‐UVB phototherapy; vitiligo may not act as one unit

Re‐pigmentation and stabilization are the two ultimate goals of any re‐pigmenting plan designed for vitiligo management. Furthermore, whether the improvement of some vitiligo lesions could be considered a guarantee for a similar response and/or stabilization of the rest of the lesions or not, remains to be clarified. To evaluate the behavior of non‐segmental vitiligo (NSV), while on narrow band‐ultraviolet B (NB‐UVB) phototherapy. 25 patients with stable generalized NSV were included and received NB‐UVB twice weekly. For the sake of ensuring accuracy of follow up, up to four lesions were randomly chosen in each patient and regularly measured using the point counting technique. The over‐all point counting technique of all included patients showed a significant reduction (18.5 ± 8.4 cm² to 8.2± 3.1 cm²) after 6 months of therapy (p < .001). Nine patients (36%), showed mixed response in the different lesions. Improvement was documented in some lesions, while other lesions showed no response or even worsening. No significant correlations were detected between the behavior of vitiligo during NB‐UVB and any of the demographic or clinical data of the patients. NB‐UVB is a pillar in the management of vitiligo, however close follow‐up of the patient as a whole and his lesions, by both subjective and objective measures are mandatory to detect activity as early as possible, as vitiligo at many times may not act as one unit. This early detection of activity and the subsequent change in the treatment policy may ultimately change the final outcome of treatment.     

A pilot study of pharmacokinetically guided dosing of oral methotrexate in the initial phase of psoriasis treatment

Background Clinical studies of low‐dose oral methotrexate (MTX) in the treatment of psoriasis and rheumatoid arthritis document a large interpatient variability in the pharmacokinetics of MTX, including its polyglutamates (MTXPGs) in erythrocytes (RBC). This can be a factor contributing to the variability of therapeutic and toxic effects. Aim This pilot trial aimed to investigate the MTXPG concentrations in RBC as well as their relation to therapeutic and adverse effects during the initial 4 months of pharmacokinetically guided therapy with a divided‐dose schedule (three doses of MTX separated by 12‐h intervals once a week). Subjects and methods Sixteen psoriatic patients (4 men and 12 women; mean age, 53 years; range, 28–69 years) with moderate‐to‐severe chronic plaque psoriasis [mean Psoriasis Area and Severity Index (PASI) = 24; range, 9–42] were enrolled in the study. Concentrations of plasma MTX and that of MTXPGs in RBC were assayed using liquid chromatography methods. The area under the concentration–time curve of plasma MTX in the interval 0–8 h post‐dose (AUC_0–8 h) was measured after a test bolus dose of 10 mg, and the starting weekly dose was individualized in order to achieve the target AUC_0–8 h of 1800 nmol·h/L. The PASI, biochemistry, and haematology tests and MTXPGs levels in RBC were evaluated at baseline and at 4‐week intervals. Results The AUC_0–8 h achieved 1360 ± 425 nmol·h/L (mean ± SD: range, 778–2400 nmol·h/L). The mean (range) of individualized doses was 14.5 mg/week (7.5–22.5 mg). The mean (SD) steady‐state concentration of total MTXPGs observed between days 85 to 110 reached 113 (34.6) nmol/L (range, 66.1–174 nmol/L). The PASI decreased from 24·0 ± 8.0 (mean ± SD) at baseline to 8.0 ± 6.1 at day 110 (P < 0.001). Thirteen patients (87%) achieved a greater than 50% improvement in baseline PASI, and seven (47%) experienced a greater than 75% improvement. There was no relationship between the percent improvement from baseline PASI and the steady‐state concentration of MTXPGs in RBC. All patients tolerated MTX well. Throughout the study period, there was a continuous increasing trend in the geometric mean values of the mean corpuscular volume from 92.6 to 96.4 fL (P < 0.001) and of plasma homocysteine from 9.5 to 12.3 µmol/L (P < 0.005). The geometric mean serum alanine aminotransferase (ALT) activity slightly increased from 0.49 to 0.80 µkat/L (P < 0.05). However, only two patients had the ALT activity transiently elevated above twice the upper limit of normal. Conclusion Results of this pilot trial show that the steady‐state levels of MTXPGs in RBC vary less than threefold between patients and did not correlate with the change in PASI observed after 4 months of therapy with an individualised weekly dose of MTX. Whether pharmacokinetically guided dosing can improve the results of psoriasis therapy with MTX should be prospectively tested in large controlled studies.     

A first prospective randomized controlled trial on the efficacy and safety of synchronous balneophototherapy vs. narrow‐band UVB monotherapy for atopic dermatitis

Background Data from an uncontrolled trial suggest synchronous balneophototherapy (sBPT), which simulates treatment conditions at the Dead Sea, to be effective in the management of atopic dermatitis (AD). Objectives The purpose of this prospective randomized controlled study was to compare the efficacy and safety of sBPT with narrow‐band (NB) UVB monotherapy (PT) for AD. Methods In this phase III multicentre trial, 180 patients with moderate‐to‐severe AD were allocated to two groups in a 1 : 1 ratio; group 1 received sBPT consisting of NB UVB treatment and synchronous bathing in 10% Dead Sea salt solution, group 2 monotherapy with UVB 311 nm. The confirmatory study design consisted of up to 35 treatment sessions. Primary endpoint, analysed on an intention‐to‐treat‐basis (n = 169), was the relative improvement of the severity SCORing of the Atopic Dermatitis Index (SCORAD) from baseline to the end of treatment (35 sessions or early cure). Sample‐size calculation aimed at establishing at least 15% superiority. Results SCORing of the Atopic Dermatitis Index at baseline was comparable between sBPT (61.8 ± 14.1) and PT (61.5 ± 12.4) group. At the end of therapy, a clinically relevant and statistically significant difference of 26.2% could be shown (P < 0.001). Exploratory testing showed statistically significant superiority of sBPT after 6 months. Mild adverse events more frequently occurred in the sBPT group (n = 46, PT: n = 31), whereas more patients withdrew early because of adverse events in the PT group (n = 6, sBPT: n = 2). Conclusions A clear advantage of sBPT in comparison to PT was proven. Tolerability was comparable; both treatments showed to be safe.