Most clinical trials investigating preventive and disease-modifying effects of SCIT were performed in children for only a few allergen products. In this study we observed adult patients 3 years after ...the completion of treatment with a high-dose hypoallergenic 6-grass pollen preparation.
A double-blind, placebo-controlled (DBPC) trial had proven efficacy and safety of a high-dose hypoallergenic 6-grass pollen preparation in adults. 3 years after termination of a 3-years' pre-seasonal SCIT symptom and medication scores, quality of life, and the development of new sensitizations were investigated Patients who fulfilled the same inclusion and exclusion criteria at start of the DBPC study and who had not received SCIT in the meantime served as a control group.
Symptom-medication score and symptom score were significantly reduced in the Ex-SCIT group in comparison to the control group (p = 0.000). Quality of life (RQLQ) was significantly better in the Ex-SCIT group (p = 0.000). 20 (77%) subjects of the Ex-SCIT group did not show any new sensitizations against a defined allergen panel in comparison to 3 (23%) patients of the control group.
This 3-years' controlled follow-up study in adults demonstrates long-term improvements in symptom-medication score and quality of life and reduced onset of new sensitizations after completion of SCIT.
Background
The most effective treatment modality for actinic keratosis (AK) is photodynamic therapy (PDT). Major obstacles of PDT are the need of a special illumination device and pain accompanying ...the illumination. These issues may be overcome by replacing an artificial high‐power light source with natural daylight for more extended illumination at lower light doses.
Objective
To determine whether BF‐200 ALA (a nanoemulsion gel containing 7.8% 5‐aminolaevulinic acid) is non‐inferior to MAL (a cream containing 16% methyl‐aminolaevulinate) in the treatment of mild‐to‐moderate AK with daylight PDT (dPDT). Non‐inferiority of the primary efficacy variable (total lesion clearance rate per patient's side 12 weeks after PDT) is established if the mean response for BF‐200 ALA is no worse than for MAL, within a statistical margin of Δ = −12.5%.
Methods
The study was performed as an intraindividual comparison with 52 patients in seven centres in Germany and Spain. Each patient received one dPDT. Results include clinical endpoints as well as 1‐year follow‐up results.
Results
Twelve weeks after a single dPDT, 79.8% of the AK lesions treated with BF‐200 ALA gel and 76.5% of the lesions treated with MAL cream were completely cleared. The median of differences was 0.0 with a one‐sided 97.5% CI of 0.0, establishing non‐inferiority (P < 0.0001). Results for secondary efficacy parameters were in line with the primary outcome. Recurrence rates 1 year after the treatment were 19.9% for lesions treated with BF‐200 ALA and 31.6% for lesions treated with MAL. Adverse reactions including pain were mostly mild and transient and identical to those previously described for dPDT.
Conclusion
Daylight PDT of AK with BF‐200 ALA is well‐tolerated and non‐inferior to MAL/dPDT. The study demonstrates a trend towards higher efficacies after 3 months and significantly lower recurrence rates after 1 year follow‐up.
Summary
Background
Basal cell carcinoma (BCC) represents the most common nonmelanoma skin cancer worldwide, affecting mainly adult, fair‐skinned individuals. The World Health Organization ...distinguishes aggressive and nonaggressive forms, of which prototypical variants of the latter are primary nodular and superficial BCC.
Objectives
To demonstrate noninferiority of BF‐200 ALA (a nanoemulsion gel containing 5‐aminolaevulinic acid) compared with MAL (a cream containing methyl aminolaevulinate) in the treatment of nonaggressive BCC with photodynamic therapy (PDT). Noninferiority of the primary efficacy variable (overall patient complete response 12 weeks after last PDT) would be declared if the mean response for BF‐200 ALA was no worse than that for MAL, within a statistical margin of Δ = −15%.
Methods
The study was a randomized, phase III trial performed in Germany and the U.K. with ongoing 5‐year follow‐up. Of 281 randomized patients, 138 were treated with BF‐200 ALA and 143 with MAL. Patients received two PDT sessions 1 week apart. Remaining lesions 12 weeks after the second PDT were retreated. Illumination was performed with a red light source (635 nm, 37 J cm−2). The results shown include clinical end points and patients’ reassessment 12 months after the last PDT. The study was registered with EudraCT (number 2013‐003241‐42).
Results
Of the BF‐200 ALA‐treated patients, 93·4% were complete responders compared with 91·8% in the MAL group. The difference of means was 1·6, with a one‐sided 97·5% confidence interval of −6·5, establishing noninferiority (P < 0·0001). The results for secondary efficacy parameters were in line with the primary outcome. Recurrence rates 12 months after the last treatment were ≤ 10%.
Conclusions
Treatment of nonaggressive BCC with BF‐200 ALA‐PDT is highly effective and well tolerated with proven noninferiority to MAL‐PDT. It demonstrates low recurrence rates after 1 year of follow‐up.
What's already known about this topic?
Photodynamic therapy (PDT) using BF‐200 aminolaevulinic acid (ALA) gel is registered and highly effective in the treatment of mild‐to‐moderate actinic keratosis and field cancerization.
BF‐200 ALA gel was recently approved for the treatment of superficial and/or nodular basal cell carcinoma (BCC) unsuitable for surgical treatment.
PDT using methyl aminolaevulinate (MAL) cream is approved for the treatment of thin or nonhyperkeratotic and nonpigmented actinic keratoses, Bowen disease, and superficial and nodular BCCs when other therapies are considered less appropriate.
What does this study add?
BF‐200 ALA‐PDT is confirmed to be significantly noninferior to MAL‐PDT for the treatment of nonaggressive BCC.
Treatment‐emergent adverse events were comparable between the two patient groups, with similar or slightly lower recurrence rates for BF‐200 ALA gel compared with MAL cream after 12 months.
Plain language summary available online
Respond to this article
Summary
Background Photodynamic therapy (PDT) with 5‐aminolaevulinic acid (ALA) or its methylester methyl‐5‐aminolaevulinate (MAL) or 5‐amino‐4‐oxopentanoate was recently ranked as first‐line ...therapy for the treatment of actinic keratosis (AK) and is an accepted therapeutic option for the treatment of neoplastic skin diseases. BF‐200 ALA (Biofrontera Bioscience GmbH, Leverkusen, Germany) is a gel formulation of ALA with nanoemulsion for the treatment of AK which overcomes previous problems of ALA instability and improves skin penetration.
Objectives To evaluate the efficacy and safety of PDT of AKs with BF‐200 ALA in comparison with a registered MAL cream and with placebo.
Methods The study was performed as a randomized, multicentre, observer‐blind, placebo‐controlled, interindividual trial with BF‐200 ALA, a registered MAL cream and placebo in a ratio of 3 : 3 : 1. Six hundred patients, each with four to eight mild to moderate AK lesions on the face and/or the bald scalp, were enrolled in 26 study centres in Germany, Austria and Switzerland. Patients received one PDT. If residual lesions remained at 3 months after treatment, PDT was repeated.
Results PDT with BF‐200 ALA was superior to placebo PDT with respect to patient complete clearance rate (78·2% vs. 17·1%; P < 0·0001) and lesion complete clearance rate (90·4% vs. 37·1%) at 3 months after the last PDT. Moreover, superiority was demonstrated over the MAL cream regarding the primary endpoint patient complete clearance (78·2% vs. 64·2%; P < 0·05). Significant differences in the patient and lesion complete clearance rates and severity of treatment‐related adverse events were observed for the narrow‐ and broad‐spectrum light sources.
Conclusions BF‐200 ALA is a very effective, well‐tolerated new formulation for AK treatment with PDT and is superior to a registered MAL medication. Efficacies and adverse events vary greatly with the different light sources used.
See also the Commentary by Hauschild
Background
Actinic keratoses (AKs) are clinically significant and require therapy. Efficacy of low‐dose (0.5%) 5‐fluorouracil with 10% salicylic acid (5‐FU/SA) has been shown in randomized ...comparative trials of hyperkeratotic lesions of various grades.
Objectives
To evaluate the efficacy, tolerability and safety of low‐dose 5‐FU/SA topical solution vs. cryosurgery in patients with moderate/severe (grade II/III) hyperkeratotic AKs (NCT01358851).
Methods
In an exploratory, open, randomized study, patients with histologically confirmed moderate/severe hyperkeratotic AKs on the face/forehead or bald scalp received 6 weeks of once‐daily topical 0.5% 5‐FU/SA, or up to two cryosurgery treatments (3 weeks apart). Histological outcomes were determined from punch biopsies. Clinical, cosmetic and tolerability outcomes were also assessed.
Results
Sixty‐six patients received treatment (33 per arm). The baseline total number of lesions was 266 (8.1/patient) in the 0.5% 5‐FU/SA and 263 (8.0/patient) in the cryosurgery group. Most (74.5%) lesions were grade II (grade III, 25.5%). Mean change in lesion count from baseline to Day 98 was −5.2 and −5.7 lesions per patient for 0.5% 5‐FU/SA and cryotherapy groups respectively. Histological AK clearance rates on Day 98 were 62.1% and 41.9% respectively. At 6‐month posttreatment follow‐up, recurrence of cleared lesions (no clinically visible lesions in treatment area) occurred in 39.4% of 0.5% 5‐FU/SA and 84.8% of cryosurgery patients. Drug‐related adverse events (AEs), including local skin reactions considered ‘severe’ by the investigator, were reported in 24.2% of 0.5% 5‐FU/SA and 6.1% of cryosurgery patients. All drug‐related AEs were skin reactions.
Conclusions
Although the study was not powered to explore statistical differences in clinical efficacy between treatments, a short (6‐week) schedule of topical treatment with 0.5% 5‐FU/SA achieved greater histological clearance and lower recurrence of grade II/III hyperkeratotic AKs than cryosurgery. AE incidence across both treatment groups was relatively low and AEs were generally mild or moderate. Clinical trials.gov identifier: NCT01358851.
Summary Background Two phase III trials of photodynamic therapy (PDT) with BF‐200 ALA, a recently approved nanoemulsion formulation of 5‐aminolaevulinic acid (ALA) demonstrated high clearance rates ...in mild‐to‐moderate actinic keratosis (AK). The comparison to a registered methyl aminolaevulinate (MAL) cream demonstrated significantly superior total patient clearance rates.
Objectives To evaluate long‐term efficacy and safety of PDT for AK 6 and 12 months after the last PDT with BF‐200 ALA, MAL or placebo.
Methods The follow‐up phase (FUP) was performed with patients of two phase III studies. Both studies compared BF‐200 ALA with placebo, one of the studies additionally with MAL. Overall recurrence rates and various subgroups (light source, lesion severity, lesion location, complete responders after first PDT) were assessed 6 and 12 months after the last PDT.
Results Recurrence rates were similar for BF‐200 ALA and MAL, with a tendency to lower recurrence rates for BF‐200 ALA. The proportion of patients who were fully cleared during PDT and remained completely clear for at least 12 months after PDT were 47% for BF‐200 ALA (both studies) and 36% for MAL treatment. The subgroup that was illuminated with narrow wavelength LED lamps reached 69% and 53% for BF‐200 ALA (both studies, respectively) and 41% for MAL. No safety concerns were reported.
Conclusions The FUP data confirmed the high efficacy and safety of PDT with BF‐200 ALA. The slightly lower recurrence rates after BF‐200 ALA treatment compared with MAL treatment enhanced the better treatment outcome due to the significantly superior efficacy.
What’s already known about this topic?
•
BF‐200 ALA is a stable nanoemulsion‐based gel formulation of 5‐aminolaevulinic acid (ALA) for photodynamic therapy (PDT) of actinic keratosis (AK), which demonstrated significantly higher efficacy compared with a registered methyl aminolaevulinate (MAL) cream.
What does this study add?
•
This study gives 6‐ and 12‐month follow‐up results of two pivotal phase III studies with BF‐200 ALA for PDT of AK in comparison to placebo and a registered MAL cream.
•
It provides a comparison of recurrence rates after use of different light sources for PDT of AK.
See also the Commentary by Babilas
Summary
Background Photodynamic therapy (PDT) is increasingly used for treatment of actinic keratoses (AKs) but is a cumbersome procedure. A thin self‐adhesive patch (PD P 506 A) containing ...5‐aminolaevulinic acid (5‐ALA) was developed to facilitate PDT.
Objectives To investigate efficacy and safety of the patch in comparison with placebo–PDT (superiority design, observer‐blinded; study AK 03) and standard therapy, cryosurgery (noninferiority design, open; study AK 04).
Methods Two separate confirmatory randomized parallel‐group phase III studies were set up. In total, 449 patients with up to eight mild to moderate AK study lesions located on the head were treated in 29 German study centres (study AK 03: 103 patients; study AK 04: 346 patients).
Results Twelve weeks after treatment, 5‐ALA patch–PDT proved to be superior to placebo–PDT (P < 0·001) and cryosurgery (P = 0·007). Efficacy rates on a lesion basis were 82% (AK 03) and 89% (AK 04) for PDT, 77% for cryosurgery and 19% (AK 03) and 29% (AK 04) for placebo–PDT. Local reactions at the treatment site occurred in almost all patients treated with 5‐ALA patch–PDT or cryosurgery. Headache was the only side‐effect not related to the treatment site which occurred in more than one patient.
Conclusions PD P 506 A is an innovative, easy‐to‐handle 5‐ALA patch for PDT of mild to moderate AK lesions. Compared with current PDT procedures, pretreatment (e.g. curettage) is not needed and handling is considerably facilitated. A single PDT treatment results in efficacy rates being statistically significantly superior to placebo and cryosurgery.
BF‐200 ALA gel vs. MAL cream for BCC Morton, C.A.; Dominicus, R.; Radny, P. ...
British journal of dermatology (1951),
August 2018, 20180801, Letnik:
179, Številka:
2
Journal Article
Recenzirano
Summary
Basal cell carcinoma (BCC), also known as rodent ulcer, is the most common type of non‐melanoma skin cancer worldwide. It affects about 3–10% of people. This study from the U.K. and Germany ...aimed to find out if BF‐200 ALA gel would work as well as (is non‐inferior to) the already authorised MAL cream in the treatment of non‐aggressive BCC lesions. Both medications are applied topically (on the skin) to the tumour, which is then illuminated with a certified lamp. The illumination causes a chemical reaction that affects the cancer cells so that they eventually die. This kind of procedure is called photodynamic therapy (PDT). Patients in the study were put into the two groups by chance (randomized): 138 in the BF‐200 ALA group and 143 in the MAL group. The treatment scheme for both drugs was the same. Initially, patients had two PDTs one week apart. Four and 12 weeks after the second PDT, patients visited the doctor again, who assessed the treated lesions and patient's health. If all lesions were gone by week 12, the patient entered the 5‐year follow‐up study. In case of remaining lesions, patients received two more PDTs before entering the follow‐up. During the follow‐up, doctors monitor the health of the patients and assess if any of the treated lesions come back. The study found that there was no difference between the two groups, which means that BF‐200 ALA gel worked as well as the already approved MAL cream. In 113 of 121 patients (93.4%) treated with BF‐200 ALA and 101 of 110 patients (91.8%) treated with MAL, lesions disappeared completely. 87% of the BF‐200 ALA‐treated patients rated their satisfaction with the PDT as “very good or good”; 86% of the MAL‐treated patients said the same. Almost all patients experienced mild to moderate local side effects related to the study medications. Common side effects at the application site, which affected more than 1 of 10 patients, were pain, skin reddening (erythema), itching (pruritus), and tissue swelling (oedema). Side effects were similar for both medications. At 12‐month follow‐up, lesions reappeared in 8.4% of the BF‐200 ALA‐treated patients and in 8.5% of the MAL‐treated patients. The follow‐up is still ongoing; further results will be reported after the end of the study. This study showed that BF‐200 ALA gel is as effective and well‐tolerated as MAL cream in the treatment of non‐aggressive BCC. Based on these findings, the European Medicine Agency (EMA) granted approval for BF‐200 ALA for the treatment of non‐aggressive BCC.
Linked Article: Morton et al. Br J Dermatol 2018; 179:309–319
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