Spectrum of Seasonal Allergic Rhinitis Symptom Relief with Topical Corticoid and Oral Antihistamine Given Singly or in Combination

Sixty ragweed-sensitive volunteers participated in a 2-week study that compared symptom profiles during treatment with antihistamine (loratadine, LOR) alone, topical corticoid (beclomethasone, BEC) alone, or the two drugs combined. For 5 days commencing shortly after the beginning of the ragweed bloom, patients took no treatment while we collected baseline data. They were then randomized to one of the three treatments, receiving that treatment for the balance of the 2-week study term. Twice each day they recorded the severity of congestion, eye symptoms, running and blowing, itching, and sneezing. At the end of the study they provided an estimate of overall symptom relief, which favored combined treatment (vs LOR P = 0.001, vs BEC P = 0.042). To gain an estimate of disease severity and treatment effectiveness over time, and to smooth out day-to-day variation, we divided symptom diary reports into three segments (days 2-4, 5-7, and 8-10) for From The Upjohn Research Clinics and Michigan State University College of Human Medicine, Department of Pediatrics and Human Development This study was conducted in a clinic wholly supported by The Upjohn Company Address correspondence and reprint requests to Dr. Carter D. Brooks, Clinical Research Director, 7000 Portage Road, Kalamazoo, M149001-0199 American Journal of Rhinology analysis. Combined treatment controlled symptoms better than antihistamine alone in nearly all study segments. Corticoid alone or combined with antihistamine provided similar control of congestion, running and blowing, and eye complaints. Combination therapy controlled itching and sneezing better, especially through the study segments 1 and 2. Patient preference for combined treatment seems to relate to control of itching and sneezing and rapid onset of effect. (American Journal of Rhinology 10, 193-199, 1996) Inseveral previous studies we have examined profiles of individual symptoms in allergic rhinitis and the selective effects of various treatments on these profiles. We showed that, compared to placebo, terfenadine suppressed sneeze, itch, and eye symptoms, benefitted congestion marginally, and failed to improve running and blowing. Of these, only control of sneezing 'appeared quickly after introduction of the drug in midseason.! Another study intended to establish minimal effective doses of oral methylprednisolone found, at 6 mg per day, significant suppression of congestion, postnasal drainage, and eye symptoms, but not itching, sneezing, and running? These fmdings could be a clinical expression of the reported inability of systemic corticoid to prevent release of mediators from human mast cells? It appeared that the symptoms most responsive to antihistamine treatment responded least well to low dose corticoid and vice versa, providing a rational basis for combination of the two drug types for seasonal allergic rhinitis 193 000001 Exhibit 1038 IPR2017-00807 ARGENTUM Delivered by Ingenta to: Tyler Liu IP: 73.172.218.95 On: Sun, 15 Jan 2017 00:35:07 Copyright (c) Oceanside Publications, Inc. All rights reserved. For permission to copy go to https://www.oceansidepubl.com/permission.htm treatment. We have carried out preliminary studies documenting additive protection with combined antihistamine/ corticoid treatment, and the equivalence of oral and topical corticoid when given as part of the combination. Others have studied symptom control with combined antihistamine/topical corticoid treatment and have reported variable findings.4-7 Most reported a more modest increment of patient-perceived benefit with combined treatment than our preliminary studies led us to expect. The goal of the study reported here was to compare profile and severity of individual symptoms, and overall patient perception of benefit during seasonal allergic rhinitis treatment with antihistamine (loratadine, Claritin, Schering-Plough, LOR) alone, topical nasal corticoid (bedomethasone, Vancenase AQ, Schering-Plough, BEC) alone, and the two drugs in combination. The study did not contain a concurrent placebo control group, but all study participants entered the treatment comparison from an untreated baseline observation period. STUDY DESIGN AND EXECUTION Subject Selection S subjects enrolled in and completed the study. Each treatment group contained 20 people; sex distribution in the LOR group was IOM/IOF, whereas the BEC and the LORIBEC groups both had 7M/13F. The three treatment groups were roughly comparable in age, height, and weight. All had reliable histories of seasonal rhinitis compatible with ragweed seasonal allergic rhinitis and strongly positive ragweed skin (prick) tests. Many had participated in previous studies and had provided records of the severity of their seasonal symptoms. None had evidence of significant complicating disease on history, physical examination, or screening laboratory testing; women had negative pregnancy tests on entry and again in mid-study. All alleged that they understood the design, demands, and risks of the study and signed their consent to participate. The Bronson Hospital Human Use Committee reviewed and approved the study design and documents.