A randomized clinical trial in psoriasis: synchronous balneophototherapy with bathing in Dead Sea salt solution plus narrowband UVB vs. narrowband UVB alone (TOMESA-study group).

BACKGROUND: Synchronous balneophototherapy (sBPT) simulates treatment conditions at the Dead Sea for outpatient use. In the past, sBPT proved to be an effective treatment for psoriasis. However, there is a lack of sufficiently large randomized controlled clinical trials evaluating the additional benefit of sBPT compared with ultraviolet B (UVB) monotherapy. OBJECTIVES: The purpose of this study was to compare the effectiveness and safety of sBPT with UVB phototherapy (PT) alone in a randomized controlled effectiveness study. METHODS: In this phase III, multicentre effectiveness study, 367 patients with moderate to severe psoriasis were randomly allocated in a 1 : 1 ratio to receive either sBPT consisting of narrowband UVB PT with 311 nm and synchronous bathing in 10% Dead Sea salt solution or PT with 311 nm alone. Primary endpoint, analysed on an intention-to-treat basis (n = 356), was the relative improvement of the Psoriasis Area and Severity Index (PASI) from baseline to end of treatment (35 sessions or clearance). Sample size calculation aimed at the detection of superiority of at least 10%. RESULTS: Median PASI values were comparable at baseline (sBPT: 15.1, interquartile range: 10.9-24.3; PT: 15.3, interquartile range: 10.0-23.7). A clinically relevant and statistically significant difference of 49.5% between sBPT and PT could be proven at the end of the therapy phase (P < 0.001; Wilcoxon-Mann-Whitney test). Exploratory testing showed a statistically significant superiority of sBPT after 6 months. CONCLUSIONS: In routine clinical practice, sBPT is superior to PT alone after 35 treatment sessions and a follow-up of 6 months. Both treatments demonstrated to be safe.

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.

Willingness to pay and time trade-off: sensitive to changes of quality of life in psoriasis patients?

BACKGROUND: Willingness to pay (WTP) and time trade-off (TTO) have been used successfully as quality of life (QOL) measurements in dermatology. However, until now there have been no studies available individually comparing these measures pre- and post-treatment. OBJECTIVES: To check sensitivity to changes for WTP and TTO (i). pre- to post-treatment, and (ii). to a 6-month follow-up period. METHODS: We performed a prospective multicentre study in outpatients with psoriasis vulgaris treated with synchronous balneo-phototherapy (simultaneous application of narrowband ultraviolet B and bathing in 10% Dead Sea salt solution). Besides WTP and TTO, the Psoriasis Disability Index (PDI) and the Psoriasis Area and Severity Index (PASI) were monitored. RESULTS: One hundred and ninety-four patients participated in the pretreatment survey, of whom 138 (71%; 84 men, 54 women; mean age 43.9 years) also returned the post-treatment questionnaire. WTP (percentage of monthly income) was shown to be independent of patients' income. During treatment, mean +/- SD WTP fell from 13.8 +/- 19.2% to 11.5 +/- 15.9% (relative improvement 16.7%; P < 0.05), TTO (h per day) from 2.7 +/- 3.8 to 2.3 +/- 3.6 (relative improvement 15%; P < 0.001), PDI improved from 29.8 +/- 18.6 to 23.5 +/- 18.9 (relative improvement 21.1%; P < 0.001) and PASI (available for 113 patients) from 14.9 +/- 7.7 to 5.6 +/- 5.0 (relative improvement 62.4%; P < 0.001). Changes in WTP, PDI and PASI were statistically significantly correlated. Ninety-one of 138 patients (66%) also completed a third survey after a follow-up period: no further changes in PDI, WTP and TTO were found, indicating a stable QOL post-treatment. CONCLUSIONS: Correlation analysis indicated that WTP, assessed as percentage of monthly income, seems to be an appropriate way to measure QOL, unbiased by income of patients. WTP, TTO and PDI were correlated and were sensitive to changes during treatment. WTP and TTO therefore also seem to be appropriate tools for assessment of QOL in interventional studies, especially for pharmacoeconomic analyses.

[How large is the loss of effectiveness of a treatment procedure between "theory" and "practice"? Evaluating health economics basic data within the scope of a trial model of ambulatory synchronous balenophototherapy of atopic eczema]. / Wie gross ist der Effektivitätsverlust eines Behandlungsverfahrens zwischen "Theorie" und "Praxis"? Evaluierung gesundheitsökonomischer Basisdaten im Rahmen des Erprobungsmodells ambulante synchrone Balneophototherapie bei atopischem Ekzem.

BACKGROUND AND OBJECTIVE: Before introducing new treatment modalities, efficacy has to be proven in clinical trials. Furthermore, it is of special interest to what extent results of clinical trials can be transferred to daily routine. PATIENTS/METHODS: In the framework of a trial on out-patient synchronous balneophototherapy, a possible loss in treatment efficacy from "clinical trial" to "daily routine" was examined. Therefore all patients without protocol deviations (representing treatment success available in a "clinical trial") and all patients with at least one treatment session regardless of protocol deviations (model for "daily routine") were analyzed. RESULTS: 257 "daily routine" and 1281 "clinical trial" patients with atopic dermatitis were analyzed. Relative SCORAD-improvements provided a clear loss in treatment efficacy in the "daily routine" group of 14.2%: 55% of patients received less than the planned 3 treatments per week and 48% left the study early because of noncompliance, good improvement, lack of time or lack of efficacy. CONCLUSIONS: For the first time a loss of efficacy of a treatment modality between "theory" and "practice" can be demonstrated in a representative number of patients suffering from atopic dermatitis. For the optimal use of rare financial resources, the comparison of different treatment modalities under "daily routine" conditions is also necessary in future.

Differences in efficacy between intention-to-treat and per-protocol analyses for patients with psoriasis vulgaris and atopic dermatitis: clinical and pharmacoeconomic implications.

BACKGROUND: Pharmacoeconomic outcome research is based on three criteria: (i) evaluation of objective therapeutic effects; (ii) quality of life; and (iii) treatment costs. Evaluation of therapeutic effect is mainly based on the results of clinical trials using objective clinical measures, e.g: Psoriasis Area and Severity Index (PASI) (score for psoriasis vulgaris) and the Severity Scoring of Atopic Dermatitis (SCORAD) (score for atopic dermatitis). In most studies, only results for a treatment-optimized subpopulation (patients treated according to the protocol) are presented in publications. The relevance of such data for daily routine therapy is doubtful. OBJECTIVES: Our purpose was to investigate the expected loss of effectiveness of switching from a clinical trial to daily routine therapy for the synchronous application of narrow-band ultraviolet (UV) B phototherapy (311 nm) and bathing in 10% Dead Sea salt solution (synchronous balneophototherapy) for patients with psoriasis vulgaris and atopic dermatitis. METHODS: We conducted a multicentre, uncontrolled observational study of outpatients. To achieve data for 'clinical trial' and 'daily routine' situations, two populations were compared: (i) all patients strictly treated according to the protocol (ATP) with no protocol deviations (data published in clinical trials), and (ii) all patients participating in the study who received active treatment at least once, despite treatment irregularities, non-compliance, early withdrawal or other protocol violations [intention-to-treat-population (ITT), model for 'daily routine']. RESULTS: A total of 2526 patients were included in the ITT analysis for psoriasis vulgaris (n = 487 for atopic dermatitis), of which 818 patients could be analysed according to protocol (n = 104 for atopic dermatitis). Striking differences in the therapeutic effect between both groups (ITT and ATP) were found using relative PASI and SCORAD score improvement: 11% (57% 'daily routine' vs. 68% in 'clinical trial') for psoriasis vulgaris and 16% (39% 'daily routine' vs. 55% 'clinical trial') for atopic dermatitis. The main reasons for excluding patients from the 'clinical trial' group were early study withdrawal in 29% (atopic dermatitis, 47%) of patients and fewer treatments per week than planned in the protocol in 24% (atopic dermatitis, 52%). CONCLUSIONS: Our data clearly indicate that for the prediction of the therapeutic effect for daily routine therapy the ITT data appear to be more relevant than the ATP results (i.e. those presented in clinical trials). Although these data are only a first step for evaluating the 'real' therapeutic effect of a treatment modality in daily routine, they seem to support the requirements for ITT analyses in efficacy studies and demonstrate the necessity of ITT data for pharmacoeconomic evaluation.

Evaluation of a multicentre study of synchronous application of narrowband ultraviolet B phototherapy (TL-01) and bathing in Dead Sea salt solution for psoriasis vulgaris.

The synchronous application of narrowband UVB phototherapy with 311 nm lamps (Philips TL-01) and bathing in Dead Sea salt solution was evaluated in a multicentre trial (n = 60) in outpatients suffering from psoriasis vulgaris. The study design consisted of an initial therapy phase of up to 35 treatments (three to five times a week) followed by maintenance therapy with up to 35 further applications (once or twice a week). Evaluation was performed separately for patients in according-to-protocol (ATP) (n = 280) and intention-to-treat (ITT) (n = 692) groups. An overall significant improvement of the Psoriasis Area and Severity Index (PASI) score (P < 0.05) could be shown for both groups during initial therapy with 71.4% improvement for ATP and 61% for ITT patients. The mean PASI for ATP (values for ITT in parentheses) was 17.7 (18.6) at baseline, 9.5 (10.7) after 20 applications and 5.2 (7.4) at the end of initial therapy. On average, ATP patients received 3.9 (3.5) applications per week with a cumulative irradiation dose of 19.5 J cm-2 (16.2 J cm-2). The most frequent side-effect was erythema, observed in 8.7% of the patients. Subjective evaluation of the therapy by the patients (n = 168) was excellent. Seventy-nine per cent of patients preferred the new treatment strategy in comparison with other previous therapies and 88% regarded this therapy as pleasant and comfortable. In conclusion, we could demonstrate a significant effect of therapy in both the ATP and the ITT groups for this new treatment system which imitates, as far as possible, the Dead Sea climatic conditions, with no severe side-effects and a high acceptance by the patients.