Comparative study on the efficacy and safety of bepotastine besilate versus levocetirizine in chronic spontaneous urticaria: A randomised, open-label, parallel study.

Background Urticaria is a common skin disease which often causes impairment in the quality of life. The ideal drug for chronic urticaria would have antihistaminic and anti-inflammatory actions. Bepotastine besilate is a recently approved novel anti-allergic agent with multiple mechanisms of action; levocetirizine is a potent and selective second-generation H1 receptor antagonist used in the treatment of urticaria. Aim To compare the efficacy and safety of bepotastine besilate versus levocetirizine in patients with chronic spontaneous urticaria. Methods The study design is a randomised, open-label, parallel-group, prospective interventional study. The study subjects were randomly assigned to either of the two groups a and b, each group had 50 patients with chronic urticaria. Statistical analyses were performed using (SPSS, version 18) for all the variables. Chi-square test was used for comparison between categorical variables. An unpaired student's t-test was done for quantitative variables. Results There was a significant decrease in mean urticaria activity score (P < 0.001), chronic urticaria quality of life (P < 0.001) and clinical global improvement (P < 0.001) in both the treatment groups but this improvement was higher in the bepotastine than in the levocetirizine group. There was no significant difference in the mean of absolute eosinophil count, C-reactive protein, aspartate transaminase, alanine transaminase from baseline to 4th week between the two study groups. Visual analogue scale showed statistically significant improvement from baseline to 4th week (P < 0.001) of follow-up but this increase was higher in levocetirizine group (0.64-4.24) than in bepotastine group (0.56-2.56) Limitations Blinding was not done. To assess the efficacy and safety of bepotastine, a larger study can be planned. Conclusion This study found that bepotastine is superior to levocetirizine and showed a statistically significant reduction in mean urticaria activity score 7, improved quality of life and clinical global improvement in patients with urticaria.

The therapeutic role of methotrexate in chronic urticaria: A systematic review.

BACKGROUND: Chronic urticaria, in many cases, has an unsatisfactory response to antihistamines. The current recommendations in urticaria do not mention the dose and duration for methotrexate. AIMS: This study aims to systematically review the use/efficacy of methotrexate in chronic urticaria. METHODS: A systematic search in four databases, that is, PubMed/Medline, Cochrane central, Google Scholar and Clinicaltrials.gov was done to identify studies on the use of methotrexate in chronic urticaria using key words "methotrexate [MeSH terms]" and "urticaria" or "urticaria, chronic" or "urticaria, chronic spontaneous." RESULTS: Nine articles (study participants 127), including three randomized control trials, one prospective interventional trial without control, three retrospective reviews and two case reports, were identified and finally included in the systematic review. There was a paucity of literature and the three randomized control trials did not show any benefit of methotrexate over antihistamines alone. However, in studies where steroid-dependent cases were given methotrexate, marked benefit was reported with steroid-sparing effect, particularly on methotrexate dose escalation. LIMITATIONS: Due to a paucity of published literature on methotrexate in urticaria, a meta-analysis could not be done. CONCLUSION: In chronic recalcitrant or steroid-dependent cases, methotrexate may be a therapeutic agent of interest; however, current evidence does not point to any added advantage in efficacy over antihistamines. More evidence based on larger, well-executed randomized control trials is needed in the future to get more definitive answers.

Effectiveness and safety of levocetirizine 10 mg versus a combination of levocetirizine 5 mg and montelukast 10 mg in chronic urticaria resistant to levocetirizine 5 mg: A double-blind, randomized, controlled trial.

BACKGROUND: Chronic urticaria is a vexing problem for patients and treating physicians alike. The EAACI/GA[2]LEN/EDF/WAO guidelines advocate an increased antihistamine dosage up to four times the standard, before adding leukotriene receptor antagonists. Patients are frequently intolerant of these higher dosages. We conducted this study to determine whether the addition of leukotriene receptor antagonists to the standard antihistamine dose was comparable to higher dosages of antihistamines alone, in terms of efficacy, safety and quality of life changes. We compared levocetirizine 10 mg (double dose of standard) versus a combination of levocetirizine 5 mg and montelukast 10 mg in cases of chronic urticaria not responding to single daily dose of 5 mg levocetirizine. METHODS: A single-center, double-blind, randomized, active-controlled, parallel group phase IV trial (CTRI/2014/12/005261) was conducted on 120 patients of chronic urticaria of either sex not responding to 5 mg levocetirizine. Patients were randomized into receiving either levocetirizine 10 mg or levocetirizine 5 mg + montelukast 10 mg for 4 weeks. Primary outcome measures were Urticaria Activity Score (UAS) and Urticaria Total Severity Score (TSS). Routine hematological and biochemical tests and treatment-emergent adverse events were monitored for safety. RESULTS: Fifty-two patients on levocetirizine 10 mg group and 51 patients on levocetirizine 5 mg + montelukast 10 mg group were analyzed. UAS and TSS reduced significantly in both treatment groups and reduction of score were comparable in between the groups (P = 0.628, P = 0.824, respectively). Among adverse effects, sedation was noted significantly more (P = 0.013) in levocetirizine 10 mg group. Quality of life was significantly improved in levocetirizine 5 mg + montelukast 10 mg group (P = 0.031). LIMITATIONS: The limitation of the study was that the follow-up period was 4 weeks. CONCLUSION: EAACI/GA[2]LEN/EDF/WAO guidelines need to be more flexible in allowing usage of montelukast before escalation of anti-histamine dosage.

A randomized placebo-controlled double-blind pilot study of methotrexate in the treatment of H1 antihistamine-resistant chronic spontaneous urticaria.

BACKGROUND: Chronic urticaria not responsive to antihistamines is a difficult disease to manage. Methotrexate has been used in difficult chronic urticarias with some benefit. OBJECTIVE: To evaluate the efficacy of methotrexate in the treatment of chronic spontaneous urticaria poorly responsive to H1 antihistaminics. METHODS: In a randomized double-blind trial at the Department of Dermatology and Venereology of a tertiary care centre, 29 patients with chronic spontaneous urticaria not responding well to H1 antihistaminics were recruited. Patients were randomly allocated to receive either a weekly dose of oral methotrexate 15 mg or placebo (calcium carbonate) for a total duration of 12 weeks, after which treatment was stopped and patients were followed up for relapse of urticaria. Each group also received levocetrizine 5 mg once daily for symptom control. Primary outcome measured was a reduction by >2/3 rd of baseline urticaria scores after 12 week therapy. Secondary outcome was a reduction in antihistamine requirement after stopping therapy. RESULTS: Fourteen patients were randomized to the methotrexate group and fifteen patients to the placebo group. Out of 17 patients who completed therapy, the primary outcome was achieved by 3.5 ± 1.9 (out of 10) patients in the methotrexate group and by 3.67 ± 1.03 (out of 7) patients in the placebo group (P > 0.05). Ten patients followed up, after stopping therapy, for a mean period of 3.5 ± 2.4 months; 3 remained in remission and 7 had relapsed. One patient had uncontrollable nausea and vomiting after taking methotrexate and was withdrawn from the study. The placebo group did not experience any side effects. CONCLUSIONS: Methotrexate 15 mg weekly for 3 months did not provide any additional benefit over H1 antihistamines in this study but an adequately powered study with longer follow up is required to assess its utility.

Chronic urticaria in patients with autoimmune thyroiditis: significance of severity of thyroid gland inflammation.

BACKGROUND: There is a clear association between autoimmune thyroiditis (AT) and chronic urticaria/angioedema (CUA). However, not all patients with AT demonstrate urticaria. AIMS: The aim of the study was to investigate in which patients with AT did CUA become a problem. A sensitive inflammation marker, neopterine (NP) was used to confirm whether the severity of inflammation in the thyroid gland was responsible for urticaria or not. METHODS: Neopterine levels were assessed in patients with AT with urticaria and without urticaria. Furthermore, levels were compared in relation to pre and post levothyroxine treatment. Twenty-seven patients with urticaria (Group 1) and 28 patients without urticaria (Group 2) were enrolled in the study. A course of levothyroxine treatment was given to all patients, and urine neopterine levels before and after the trial were obtained. RESULTS: All patients completed the trial. Mean age in Group 1 and Group 2 was similar (35.70 ± 10.86 years and 38.36 ± 10.38 years, respectively) (P=0.358). Pre-treatment urine neopterine levels were significantly higher in Group 1 (P=0.012). Post-treatment levels decreased in each group, as expected. However, the decrease in the neopterine level was insignificant in the patients of Group 2 (P=0.282). In Group 1, a significant decrease in post-treatment neopterine levels (P=0.015) was associated with the remission of urticaria. CONCLUSION: In patients with CUA and AT, pre-treatment elevated levels of NP, and its decrease with levothyroxine treatment along with symptomatic relief in urticaria, may be evidence of the relationship between the degree of inflammation in thyroid and presence of urticaria.

Histamine 2 blocker potentiates the effects of histamine 1 blocker in suppressing histamine-induced wheal.

BACKGROUND: Histamine is responsible for the wheal and flare reaction in various allergic conditions. Classical antihistamines are the drugs which block the H 1 receptors and are widely used in various allergic conditions, whereas H 2 blockers are mainly used for acid peptic disease. Although H 1 receptor-mediated actions of histamine are primarily responsible for vasodilatation, vasopermeability, and itching, it has been observed that combined blocking of both H1 and H2 receptors may provide better relief. AIM: To compare the efficacy of levocetirizine (H1 blocker) versus levocetirizine and ranitidine (H2 blocker) in suppressing histamine-induced wheal. METHODS: Fifteen volunteers were given a single dose of levocetirizine 5 mg on day 1 and a single dose of levocetirizine 5 mg with ranitidine 150 mg twice a day on day 7. A pretest was performed by intradermal histamine prick test. After administration of the drugs, the prick test was repeated at 1 hour, 2, 3, 6, and 24 hours, and the size of the wheal measured and statistically analyzed. RESULTS: At 1 hour, there was no statistically significant difference in the wheal size between levocetirizine alone and the combination of levocetirizine and ranitidine. Levocetirizine with ranitidine resulted in statistically significant reduction of wheal size at 2, 3, 6, and 24 hours when compared with levocetirizine alone. CONCLUSION: H2 blocker potentiates the effects of an H1 blocker in suppressing histamine-induced wheal.