Local Application Site Reactions Research Articles

Consistent efficacy and safety of sublingual immunotherapy tablets across allergens and geographic regions.

The clinical development program of the SQ grass, ragweed, tree, and house dust mite (HDM) sublingual immunotherapy (SLIT)-tablets for allergicrhinitis/conjunctivitis (AR/C) included clinical trials conducted in North America,Europe, and Japan. Data from these trials were analyzed to assess efficacy, immunologic mechanisms, and safety outcomes acrossallergens and geographic regions. Thirteen phase III, double-blind, placebo controlled trials in the subjects with AR/C were conducted in NorthAmerica, Europe (including Russia), and Japan (N = 7763 analyzed). Trials were generally similar with respect to medicalpractice, target population, eligibility criteria, and efficacy and safety monitoring. Data were analyzed for the approved dosesin North America and Europe. Four statistical models were used to enhance comparison of the efficacy end points among the trials. The SLIT-tablets demonstrated consistent efficacy across allergens and regions, regardless of the statistical analysis used. Relative improvement in the primary efficacy end point compared with placebo by using the predefined protocol analysis ranged from 17.9% to 32.8%, 17.5% to 19.3%, 20.6% to 38.3%, and 39.6% with the grass, HDM, ragweed, and tree SLIT-tablets, respectively. The kinetics of specific immunoglobulin E (IgE) and IgG4 responses were similar among the allergensand regions. Local application-site reactions were the most common adverse events for all allergens and in all regions. Mosttreatment-related adverse events for all allergens and in all regions were mild in severity. The rate of systemic allergic reactions was similar across regions (0%-0.54%). Confirmatory phase III trials for SLIT-tablets in the treatment of AR/C showed consistent efficacy, immunologic,and safety outcomes across allergens and geographic regions.

Guidelines for pharmacotherapy in Alzheimer's disease - A primer on FDA-approved drugs.

The growing prevalence of dementia makes it important for us to better understand its pathophysiology and treatment modalities, to improve the quality of life of patients and caregivers. Alzheimer's disease (AD), a neurodegenerative disease, is the most common form of amnestic dementia in the geriatric population. Pathophysiology of AD is widely attributed to aggregation of amyloid-beta (Aβ) plaques and hyperphosphorylation of tau proteins. Initial treatment modalities aimed to increase brain perfusion in a non-specific manner. Subsequent therapy focused on rectifying neurotransmitter imbalance in the brain. Newer drugs modify the progression of the disease by acting against aggregated Aβ plaques. However, not all drugs used in therapy of AD have been granted approval by the United States Food and Drug Administration (FDA). This review categorizes and summarizes the FDA-approved drugs in the treatment of AD in a manner that would make it a convenient reference for researchers and practicing physicians alike. Drugs that mitigate symptoms of dementia may be categorized into mitigators of Behavioral and Psychological Symptoms of Dementia (BPSD), and mitigators of cognitive decline. BPSD mitigators include brexpiprazole, an atypical antipsychotic with a once-daily dosage suited to treat agitation in dementia patients, and suvorexant, an orexin receptor antagonist used to treat sleep disturbances. Cognitive decline mitigators include cholinesterase inhibitors such as donepezil, rivastigmine, and galantamine and glutamate inhibitors such as memantine. Donepezil is the most commonly prescribed drug. It is cheap, well-tolerated, and may be prescribed orally once daily, or as a transdermal patch once weekly. It increases ACh levels, enhances oligodendrocyte differentiation and also protects against Aβ toxicity. However, regular cardiac monitoring is required due to reports of cardiac conduction side effects. Rivastigmine requires a twice-daily oral dosage or once-daily replacement of transdermal patch. It has fewer cardiac side effects than donepezil, but local application-site reactions have been noted. Galantamine, in addition to improving cognitive symptoms in a short span of time, also delays the development of BPSDs and has minimal drug-drug interactions by virtue of having multiple metabolic pathways. However, cardiac conduction disturbances must be closely monitored for. Memantine, a glutamate regulator, acts as an anti-Parkinsonian agent and an antidepressant, in addition to improving cognition and neuroprotection, and requires a once-daily dosage in the form of immediate-release or sustained-release oral tablets. Disease-modifying drugs such as aducanumab and lecanemab reduce the Aβ burden. Both act by binding with fibrillary conformations of Aβ plaques in the brain. These drugs have a risk of causing amyloid-related imaging abnormalities, especially in persons with ApoE4 gene. Aducanumab is administered once every 4 weeks and lecanemab once every 2 weeks. The decision on the choice of the drug must be made after considering the availability of drug, compliance of patient (once-daily vs. multiple doses daily), cost, specific comorbidities, and the risk-benefit ratio for the particular patient. Other non-pharmacological treatment modalities must also be adopted to have a holistic approach toward the treatment of AD.

House dust mite sublingual immunotherapy tablet safety in adolescents with allergic rhinoconjunctivitis: Worldwide clinical trial results

BackgroundThe house dust mite (HDM) sublingual immunotherapy (SLIT)-tablet is a treatment option for allergic rhinitis with/without conjunctivitis (AR/C) approved in adults worldwide and in adolescents in some countries. ObjectiveTo supplement existing adolescent HDM SLIT-tablet safety data by conducting the MT-18 trial in adolescents. MethodsMT-18 (EudraCT:2020-000446-34) was a phase 3, open-label, single-arm, 28-day safety trial of daily HDM SLIT-tablet (12 SQ-HDM dose) in European adolescents (12-17 years) with HDM AR/C, with or without asthma. The primary end point was at least 1 treatment-emergent adverse event (TEAE). MT-18 results were compared with 12 SQ-HDM adolescent subpopulation data from previously described 1-year phase 3 trials conducted in North America (P001; clinicaltrials.gov:NCT01700192) or Japan (TO-203-3-2; JapicCTI:121848). ResultsNo treatment-related anaphylaxis, epinephrine administrations, severe local swellings, severe mouth or throat edema, or eosinophilic esophagitis occurred in the trials. For MT-18 (N = 253), P001 (N adolescents = 189), and TO-203-3-2 (N adolescents = 206), the percentage of adolescents treated with 12 SQ-HDM reporting any TEAE was 88%, 95%, and 93%, respectively, and the percentage reporting any treatment-related AE (TRAE) was 86%, 93%, and 66%, respectively. The most common TRAEs were local application site reactions. Most TRAEs were mild in intensity and were typically experienced the first 1 to 2 days of treatment. There were no asthma-related TEAEs with the HDM SLIT-tablet. The safety profile appears similar between adolescents with or without asthma at baseline. ConclusionThe HDM SLIT-tablet was well tolerated in European, North American, and Japanese adolescents with HDM AR/C, indicating safety of the HDM SLIT-tablet is insensitive to age or geographic region. Trial registrationClinicalTrials.gov Identifier: (P001: NCT01700192); EudraCT: (MT-18; 2020-000446-34); JapicCTI: (TO-203-3-2; 121848)

OPEN-LABEL SAFETY TRIAL OF HOUSE DUST MITE SUBLINGUAL IMMUNOTHERAPY TABLET IN ADOLESCENTS WITH ALLERGIC RHINITIS/RHINOCONJUNCTIVITIS

<h3>Introduction</h3> The HDM sublingual immunotherapy (SLIT) tablet is a treatment option for allergic rhinitis with/without conjunctivitis (AR/C) approved in adults worldwide and in adolescents in some countries. The MT-18 trial was conducted specifically in adolescents per FDA request to supplement existing adolescent safety data of the HDM SLIT tablet. <h3>Methods</h3> MT-18 (EudraCT:2020-000446-34) was a phase 3, open-label, single-arm, multi-center, 28-day safety trial of daily HDM SLIT tablet (12 SQ-HDM dose) conducted in European adolescents (12-17 y; N=253) with HDM-associated AR/C, with or without asthma. The primary endpoint was at least 1 treatment-emergent adverse event (TEAE). Secondary endpoints were at least 1 solicited TEAE, at least 1 treatment-related adverse event (TRAE), and at least 1 serious TEAE. <h3>Results</h3> The percentage of adolescents reporting any TEAE was 88%, the percentage reporting any TRAE was 86%, and there were no serious TEAEs. Two subjects (1%) discontinued due to AEs. The most common TRAEs were local application site reactions. Most TRAEs were mild in severity and were typically experienced during the first 1-2 days of treatment. The most common TRAEs recurred for <10 days in MT-18. No treatment-related anaphylaxis, epinephrine administrations, severe local swellings, severe mouth or throat edema, or eosinophilic esophagitis occurred in the trial. <h3>Conclusions</h3> There were no new or unexpected safety findings in MT-18 compared with previous safety data. The HDM SLIT tablet was well tolerated in European adolescents with HDM AR/C, similar to previous data in North American adolescents.

A randomized, controlled, feasibility study of RD-X19 in subjects with mild-to-moderate COVID-19 in the outpatient setting.

The RD‐X19 is an investigational, handheld medical device precisely engineered to emit blue light through the oral cavity to target the oropharynx and surrounding tissues. At doses shown to be noncytotoxic in an in vitro three‐dimensional human epithelial tissue model, the monochromatic visible light delivered by RD‐X19 results in light‐initiated expression of immune stimulating cytokines IL‐1α and IL‐1β, with corresponding inhibition of severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) replication. A single exposure of 425 nm blue light at 60 J/cm2 led to greater than 99% reductions against all SARS‐CoV‐2 strains tested in vitro, including the more transmissible (Alpha) and immune evasive (Beta) variants. These preclinical findings along with other studies led to a randomized, double‐blind, sham‐controlled early feasibility study using the investigational device as a treatment for outpatients with mild to moderate coronavirus disease 2019 (COVID‐19). The study enrolled 31 subjects with a positive SARS‐CoV‐2 antigen test and at least two moderate COVID‐19 signs and symptoms at baseline. Subjects were randomized 2:1 (RD‐X19: sham) and treated twice daily for 4 days. Efficacy outcome measures included assessments of SARS‐CoV‐2 saliva viral load and clinical assessments of COVID‐19. There were no local application site reactions and no device‐related adverse events. At the end of the study (day 8), the mean change in log10 viral load was −3.29 for RD‐X19 and −1.81 for sham, demonstrating a treatment benefit of −1.48 logs (95% confidence internal, −2.88 to −0.071, nominal p = 0.040). Among the clinical outcome measures, differences between RD‐X19 and sham were also observed, with a 57‐h reduction of median time to sustained resolution of COVID‐19 signs and symptoms (log rank test, nominal p = 0.044).

Food allergy: Epicutaneous immunotherapy.

The goal of allergen-specific immunotherapy for treatment of immunoglobulin E (IgE) mediated food allergy is to safely and effectively modify the allergic response, providing protection against anaphylaxis via ongoing exposure to the triggering allergen. Targeted allergen exposure via application of allergen to the epidermis has emerged as a potentially promising approach to desensitization. Epicutaneous immunotherapy (EPIT) uses allergen embedded on an adhesive patch secured to the skin. This allows for long-lasting allergen exposure, with subsequent antigen uptake and trafficking by skin antigen-presenting cells to regional lymph nodes, which produce immunomodulatory effects in a manner that is noninvasive and limits exposure of allergen to the systemic circulation when applied to intact skin. As such, EPIT is overall well tolerated; local application site reactions are common, but systemic adverse effects are infrequent compared with other forms of immunotherapy. For peanut allergy, EPIT may increase the dose-triggering threshold in some individuals with peanut-allergy, especially younger children, but induction of remission has not been closely studied, and reliable predictors of clinical response are lacking. With U.S. Food and Drug Administration approved treatment for peanut allergy now available, the precepts of shared decision-making will be crucial in discussions with patients and their families with regard to treatment options.

Ragweed allergy immunotherapy tablet MK-3641 (Ragwitek®) for the treatment of allergic rhinitis

ABSTRACTIntroduction: Allergic rhinitis (AR) is among the most common chronic conditions affecting both children and adults. It is the cause of significant morbidity from the symptoms and interference with sleep. It results in major impairment of performance both at school and at work. In the U.S. and certain parts of Europe, ragweed pollen is a major cause of seasonal AR. In 2014, the U.S. Food and Drug Administration (FDA) approved a sublingual ragweed tablet (MK-3641) for use in adults with ragweed-induced AR.Areas covered: This paper will review the impact of ragweed-induced AR and available treatments including subcutaneous immunotherapy and studies with MK-3641. The principal search method was PubMed.Expert commentary: One dosing finding, two 28-day safety and two 52-week safety and efficacy studies have been conducted with MK-3641. The 12-U (12μg Amb a 1) tablet was the most effective. Local application site reactions were common but usually not serious. Only one, non-serious systemic reaction was reported in four safety studies. MK-3641 is a safe and effective treatment for ragweed-pollen-induced AR when treatment is initiated ≥ 12 weeks prior to the onset of the ragweed pollen season.

ADVERSE EVENT PROFILE OF SQ HOUSE DUST MITE SUBLINGUAL IMMUNOTHERAPY TABLET AFTER TREATMENT INTERRUPTION

Introduction The SQ house dust mite (HDM) sublingual immunotherapy (SLIT)-tablet is approved for daily administration for the treatment of HDM-induced allergic rhinitis. The adverse event (AE) profile following treatment interruption was evaluated. Methods Safety data from 2 DBPC trials were pooled and analyzed for AEs reported at any point after a treatment interruption of ≥ 2 consecutive days for any reason. Data for the Europe/US approved dose 12 SQ-HDM (n=783) and placebo (n=782) are presented. IRB approval was obtained. Results In all, 977/1565 subjects (62%; 476/783, 12 SQ-HDM; 501/782, placebo) reported a treatment interruption for any reason. Median interruption duration was 7 days for 12 SQ-HDM and 8 days for placebo. The proportion of subjects who experienced AEs at any point after treatment re-initiation was similar between 12 SQ-HDM (226/783 [29%]) and placebo (203/782 [26%]). Most AEs after treatment re-initiation were assessed by the investigator as mild or moderate in severity. No systemic allergic reactions, epinephrine administrations, or severe local swellings were reported after treatment re-initiation. In the 12 SQ-HDM group, the most frequently reported AEs after re-initiation were oral pruritus (8%), throat irritation (8%), and ear pruritus (7%); the frequencies of these AEs with placebo were 1%, 2%, and 1%, respectively. This AE profile characterized by local application site reactions is consistent with the known safety profile of the SQ HDM SLIT-tablet. Conclusions Safety data after short-term interruption of SQ HDM SLIT-tablet treatment do not indicate a safety signal after tablet re-initiation. The safety profile after long-term treatment interruption was not determined.

SQ house dust mite sublingual immunotherapy tablet subgroup efficacy and local application site reaction duration

BackgroundAllergic rhinitis with or without conjunctivitis (AR/C) is common, necessitating evaluation of SQ house dust mite (HDM) sublingual immunotherapy (SLIT)-tablet efficacy in various subgroups. ObjectiveTo evaluate 12 SQ-HDM efficacy and safety across subgroups, and the onset, duration, and recurrence of local application site reactions. MethodsSubgroup (age, sex, race, asthma status, and allergen sensitization) efficacy was assessed using pooled data from 2 previously described trials of daily 12 SQ-HDM vs placebo for AR/C (n = 2,138). Efficacy was measured by average total combined rhinitis score (TCRS; rhinitis daily symptom plus medication score) during the last 8 weeks of treatment. Safety in subgroups and local application site reaction onset, duration, and recurrence were evaluated using pooled data from 5 previously described trials of SQ HDM SLIT-tablet (n = 2,923). ResultsSignificant (based on 95% confidence intervals [CIs]) reduction in TCRS was seen with 12 SQ-HDM relative to placebo across all subgroups, with TCRS improvements ranging from 15% to 25%. The AE profile was generally similar within subgroups. Approximately 95% of local application site reactions were mild to moderate in severity. Median duration on day 1 of treatment for the most common local application site reactions (throat irritation, oral pruritus, ear pruritus, and lip swelling) ranged from 30 to 60 minutes; median first day of onset ranged from days 1 to 4 of treatment; median days that reactions recurred ranged from 3 to 12 days. ConclusionTreatment with 12 SQ-HDM consistently improved symptoms and was well tolerated in relevant subgroups of subjects with HDM AR/C. Local application site reactions to 12 SQ-HDM were typically mild to moderate and transient.

Impact of Adverse Event Solicitation on the Safety Profile of SQ House Dust Mite Sublingual Immunotherapy Tablet

It has been recommended that sublingual immunotherapy (SLIT) safety be assessed using solicited adverse event (AE) collection methods. The objectives of this study were to describe the impact on the safety profile of SQ house dust mite (HDM) SLIT-tablet (12 SQ-HDM dose) when prespecified local application site reactions were solicited versus unsolicited, and discuss ramifications of AE solicitation. Subjects were randomized to daily 12 SQ-HDM or placebo for up to 52 weeks in 4 double-blinded, multicenter trials. In one trial (NCT01700192; N= 1272), subjects documented daily the presence or absence of 15 World Allergy Organization-defined local application site reactions using a structured questionnaire of closed-ended questions (solicited AEs). Subjects in the other trials were not asked about specific AEs (unsolicited AEs), and AE data were pooled (N= 1287). Analysis was limited to adults aged 18 to 65 years. Whether AEs were solicited or unsolicited, the most common AEs leading to study discontinuation with 12 SQ-HDM were throat irritation and oral pruritus. Approximately 95% of treatment-related AEs were mild to moderate. Placebo-subtracted frequencies of local application site reactions associated with 12 SQ-HDM were higher when solicited versus unsolicited (ie, throat irritation, 46% vs 13%, respectively; oral pruritus, 47% vs 17%; ear pruritus, 40% vs 4%; mouth swelling, 8% vs 2%; tongue ulceration, 10% vs 0%; mouth ulceration, 7% vs <1%). Qualitatively, the safety profile of 12 SQ-HDM was similar when AEs were solicited versus unsolicited; hence, solicitation did not alter the safety profile. Higher observed frequencies of local application site reactions with AE solicitation may be partly due to suggestive reporting bias, as observed in placebo-treated subjects.

NGX-4010, a Capsaicin 8% Dermal Patch, for the Treatment of Painful HIV-associated Distal Sensory Polyneuropathy

To evaluate the efficacy, safety, and tolerability of repeated NGX-4010 treatments in the open-label extension phase of a 52-week study in patients with neuropathic pain due to HIV-associated distal sensory polyneuropathy (HIV-DSP). Patients completing the 12-week, randomized, double-blind phase of the study could enter a 40-week, open-label phase, and receive up to 3, 60-minute NGX-4010 treatments. Patients recorded their "average pain for the past 24 hours" daily using the Numeric Pain Rating Scale (NPRS). Efficacy assessment included the percentage NPRS score reduction from baseline to weeks 2 to 12 after the final treatment, and Patient Global Impression of Change (PGIC) and Clinician Global Impression of Change (CGIC) questionnaires at study termination. Of 307 patients randomized, 272 entered the open-label phase; 81, 90, 55, and 46 received 0, 1, 2, and 3 retreatments, respectively. The mean percentage decrease in NPRS score from baseline to weeks 2 to 12 after the final treatment was similar in patients receiving single or multiple NGX-4010 treatments (-25.8%, -27.1%, -24.6%, and -22.7% for 1, 2, 3, and 4 NGX-4010 treatments, respectively). PGIC and CGIC results demonstrated a benefit of NGX-4010 treatment through to the end of the study regardless of the number of treatments received. Transient local application site reactions were the most frequently reported adverse events, and were mainly mild to moderate, nonserious, and did not increase with repeated treatment. Repeated NGX-4010 treatments were generally well tolerated and resulted in consistent reductions in HIV-DSP-associated pain and improvement in patient-reported outcomes.

Randomized, double-blind, placebo-controlled trial of standardized ragweed sublingual-liquid immunotherapy for allergic rhinoconjunctivitis

Sublingual immunotherapy with liquid extracts provides an appealing alternative to subcutaneous immunotherapy for the treatment of allergic rhinoconjunctivitis (ARC), but a lack of robust evidence has deterred its use in North America. To determine the efficacy and tolerability of standardized glycerinated short ragweed sublingual allergen immunotherapy liquid (RW-SAIL) extract in subjects with ragweed-related ARC. This phase 3, randomized, placebo-controlled trial was conducted in North America. Subjects (age range, 18-55 years) with or without asthma were selected based on ARC symptom severity and erythema skin prick reaction to short ragweed. Subjects self-administered the maximum tolerated dose of RW-SAIL (n = 218) or placebo (n = 211) daily beginning approximately 8 to 16 weeks before and through the end of the ragweed pollen season. The primary end point was subject-assessed total combined daily rhinoconjunctivitis symptom and medication scores (TCS). During the entire season, there was a 43% decrease in TCS in subjects treated with RW-SAIL compared with placebo. Similar decreases were observed in TCS between the 2 groups during peak season (42%) and in daily symptom scores during the entire (42%) and peak (41%) seasons. The occurrence of adverse events was similar between the treatment groups; most were mild in severity. Treatment-related oromucosal local application site reactions occurred early and were transient and self-limited. No anaphylaxis occurred. This is the first successful North American confirmatory phase 3 clinical trial to demonstrate the safety and efficacy of a sublingual standardized ragweed allergen immunotherapy liquid extract for the treatment of ARC.

Randomized controlled trial of ragweed allergy immunotherapy tablet efficacy and safety in North American adults

BackgroundRagweed is an important cause of allergic rhinitis with or without conjunctivitis (AR/C) in North America and elsewhere. Allergen immunotherapy enabling safe patient self-administration is considered an unmet clinical need. Allergy immunotherapy tablet (AIT) treatment has shown promising efficacy and safety for grass allergy but has not been assessed for ragweed allergy. ObjectiveTo evaluate efficacy and safety of 2 short ragweed AIT doses in patients with AR/C. MethodsAdults with ragweed pollen–induced AR/C were randomized 1:1:1 to daily ragweed AIT (6 or 12 Amb a 1 units) or placebo before, throughout, and after ragweed season (approximately 52 weeks). Patients could use predefined allergy rescue medications in season. Efficacy end points included peak and entire season total combined score (TCS) and its components daily symptom score (DSS), and daily medication score (DMS). Safety assessments included adverse events. ResultsA total of 565 patients were randomized. During peak season, the 6– and 12–Amb a 1 unit ragweed AIT doses showed 21% (−1.76 score) and 27% (−2.24 score) improvement in TCS vs placebo (P < .05). The 6– and 12–Amb a 1 unit AIT doses significantly improved DSS and DMS vs placebo (P < .05). Peak and entire season efficacy were comparable. The 12–Amb a 1 unit AIT dose reduced peak-season TCS vs placebo by 21% and 25% in subgroups with and without local application-site reactions, respectively. Most treatment-related adverse events were mild, oral reactions; no systemic allergic reactions were reported. One patient in the 6–Amb a 1 unit group received epinephrine at an emergency facility for sensation of localized pharyngeal edema. ConclusionIn this trial, ragweed AIT was effective and well tolerated in ragweed-allergic North American adults. Trial Registrationclinicaltrials.gov Identifier: NCT00783198.

Effect of Allergy Immunotherapy Tablet in Patients with or without Local Application-Site Reactions

T U E S D A Y 809 Ragweed Allergy Immunotherapy Tablet Reduces Use of Ocular Antihistamines in Patients with Ragweed Pollen– Induced Allergic Rhinoconjunctivitis David I. Bernstein, MD, FAAAAI, Hendrik Nolte, MD, PhD, Peter Creticos, MD, FAAAAI, Amarjot Kaur, PhD, Nancy Liu, PhD, Gary D. Berman, MD, FAAAAI, Jacques Hebert, MD, Jennifer Maloney, MD; University of Cincinnati, Cincinnati, OH, Bernstein Clinical Research Center, LLC, Cincinnati, OH, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc, Whitehouse Station, NJ, Johns Hopkins University School of Medicine, Baltimore, MD, Merck, Whitehouse Station, NJ, Allergy and Asthma Specialists, Minneapolis, MN, Centre de Recherche Applique en Allergie de Quebec, Quebec City, QC, Canada. RATIONALE: Ocular allergic rhinoconjunctivitis (ARC) symptoms are bothersome, often requiring multiple daily applications of topical medications. Allergy immunotherapy is potentially an effective treatment of ocular ARC symptoms. In post-hoc analysis of data from 2 trials conducted to evaluate the effect of ragweed allergy immunotherapy tablet (AIT) treatment on ARC symptoms and rescue medication use, we characterized the effect of ragweed AIT on ocular rescue medication use. METHODS: Datawere pooled from 2 double-blind trials that randomized subjects with ragweed pollen–induced ARC with/without asthma to oncedaily ragweed AIT doses including 6 or 12 Amb a 1-U or placebo before, during, and after ragweed pollen season (RS; total treatment,z52 weeks). All subjects could use stepwise predefined allergy rescue medications, including olopatadine eye drops, during RS if prespecified symptom thresholds were met. This pooled exploratory analysis assessed effects of ragweed AIT on ARC ocular rescue medication use. RESULTS: During peak RS (15 consecutive days with highest moving average pollen count), 82/333 subjects receiving placebo used ocular olopatadine versus 55/317 and 43/311 subjects receiving ragweed AIT 6 and 12 Amb a 1-U, respectively, for reductions of 29.3% and 43.9% relative to placebo. During entire RS, 100/340 subjects receiving placebo used ocular olopatadine versus 71/324 and 61/318 subjects receiving ragweed AIT 6 and 12 Amb a 1-U, respectively, for reductions of 25.5% and 34.7% relative to placebo. CONCLUSIONS: Ragweed AIT reduced the need for ocular rescue medication throughout RS with notable reductions demonstrated during peak RS, when symptom burden can be expected to be at its worst.

Topical Polyphenon®E in the treatment of external genital and perianal warts: a randomized controlled trial

Benign external genital and perianal warts (condylomata acuminata) are disfiguring, displeasing skin tumours caused by human papillomavirus that may vitally burden affected patients and their partners. Current treatment options are still unsatisfactory due to low efficacy, high recurrence rates or an unfavourable side-effect profile. Although most recently prophylactic vaccines have been recommended for adolescent women, appropriate treatment modalities for anogenital warts are still needed. Green tea catechins exert antiviral, antioxidative, antiproliferative and immunostimulatory activity. Polyphenon E (MediGene AG, Munich, Germany), a proprietary extract of green tea leaves, was therefore investigated for the topical treatment of this frequent viral disease. To investigate Polyphenon E 15% and 10% ointment for efficacy and safety in the treatment of anogenital warts in immunocompetent men and women. Five hundred and three patients were randomized to receive either Polyphenon E 15% or 10% ointment or matching vehicle. The topical treatment was self-applied by the patients three times daily to all warts. Assessment of response and of adverse events was performed biweekly until complete clearance of all (baseline and new) anogenital warts or for up to 16 weeks. Recurrence was evaluated during a 12-week treatment-free follow-up period for patients with complete clearance. About 53% of patients treated with Polyphenon E 15% ointment showed complete clearance of all baseline and new anogenital warts, 51% for Polyphenon E 10% ointment, and 37% for vehicle (P = 0.01 and P = 0.03, respectively; two-sided Fisher's exact test; intent-to-treat population, last observation carried forward analysis). Women responded better than men, with about 60% of women and 45% of men in both active groups achieving complete clearance of all warts. Time to complete clearance was comparable for both strengths of Polyphenon E ointment. About 78% of all patients treated with either Polyphenon E 15% or 10% ointment showed wart clearance rates of 50% or better. Less than 6% and 4% of patients in the Polyphenon E 15% and 10% ointment groups experienced wart recurrence during follow-up. Polyphenon E ointments demonstrated a good safety profile with the majority of all adverse events being local application site reactions assessed as mild or moderate. Local reactions declined during continued treatment. The results indicate that Polyphenon E ointment is an efficacious and safe patient-applied topical treatment for external genital and perianal warts. Its use in intra-anal, intravaginal and cervical condylomas and other intraepithelial lesions warrants further clinical investigation.

Tacrolimus ointment is more effective than pimecrolimus cream with a similar safety profile in the treatment of atopic dermatitis: Results from 3 randomized, comparative studies

To compare the efficacy and safety of tacrolimus ointment and pimecrolimus cream in adult and pediatric patients with mild to very severe atopic dermatitis (AD). One thousand and sixty-five patients were randomized to treatment in 3 multicenter, randomized, investigator-blinded, 6-week studies. Based on the Eczema Area Severity Index (EASI), tacrolimus ointment was more effective than pimecrolimus cream at the end of the study in adults (54.1% vs. 34.9%, respectively; P < .0001), in children with moderate/severe disease (67.2% vs. 56.4%, respectively; P = .04), in the combined analysis (52.8% vs. 39.1%, respectively; P < .0001), and at week 1 in children with mild disease (39.2% vs. 31.2%, respectively; P = .04). Tacrolimus was also more effective than pimecrolimus based on the Investigator Global AD Assessment (IGADA), improvement in percentage of total body surface area affected, and improvement in itch scores (P < or = .05), with a faster onset of action. There was no significant difference in the incidence of adverse events (AEs), including application site reactions in the 2 studies involving 650 children. Adults treated with tacrolimus experienced a greater number of local application site reactions on day 1; both groups reported a similar incidence of application site reactions thereafter. More pimecrolimus-treated patients than tacrolimus-treated patients withdrew from the studies because of a lack of efficacy (P < or = .03) or adverse events (P = .002; pediatric mild). Tacrolimus ointment is more effective and has a faster onset of action than pimecrolimus cream in adults and children with AD; their safety profiles are similar.