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PRIVATE PRACTICE EXPERIENCE WITH MEPOLIZUMAB THERAPY
Abstracts: Poster Sessions / Ann Allergy Asthma Immunol 121 (2018) S22−S62
S38
T cell-derived bronchoconstrictor might be a target for treatmentresistant asthma.
P171 LANADELUMAB EFFICACY AFTER SWITCHING FROM PLACEBO: RESULTS FROM THE HELP AND HELP OPEN-LABEL EXTENSION STUDIES R. Tachdjian*,1, J. Anderson2, P. Busse3, D. Johnston4, S. Kiani5, C. Nurse6, K. Paes6, 1. Santa Monica, CA; 2. Birmingham, AL; 3. New York, NY; 4. Charlotte, NC; 5. London, United Kingdom; 6. Lexington, MA Introduction: Lanadelumab significantly reduced hereditary angioedema (HAE) attack rates versus placebo over 26 weeks in the phase 3 double-blind (DB) HELP Study (NCT02586805). Patients who completed the DB continued into the ongoing open-label extension study (OLE; NCT02741596). This interim analysis of data from 26May201601Sept2017 evaluated lanadelumab efficacy in the OLE among patients who received placebo in the DB. Methods: Patients from the DB placebo group received a single 300 mg lanadelumab dose on Day 1 of the OLE. Following their first attack, they received lanadelumab 300 mg every 2 weeks. Results: 33 patients from the DB placebo group entered the OLE. Their median time on study in the OLE was 8.6 months (range 6.6-12.6 months); all patients completed ≥ 6 months’ time on study, and 14 (42.4%) patients completed ≥ 9 months. During the DB run-in and treatment periods, patients had a median attack rate of 2.90 and 1.82 attacks/month, respectively (Figure). During the OLE, the median attack rate was 0.10 attacks/month. The median change in attack rate between the DB and OLE treatment periods was ¡1.38 attacks/month (¡98.5%). Conclusions: Consistent with the DB results, there was a significant reduction in attack rate with lanadelumab treatment among patients who previously received placebo. Attack rates in the DB and OLE studies
P201 PRIVATE PRACTICE EXPERIENCE WITH MEPOLIZUMAB THERAPY C. Randolph*, SOUTHBURY, CT Introduction: Mepolizumab or anti-IL-5 is a therapeutic agent recently approved for intractable moderate to severe asthma despite optimal oral and inhaled therapy. It has been demonstrated to diminish asthma exacerbations. It is administered monthly 100mg subcutaneously as a single dose. We review our experience with 16 patients with moderate to severe asthma over a 1-2 year period. Methods: Patients with moderate to severe asthma in a currently two provider allergy /immunology private practice initiated on mepolizumab over a 1-2 year period were followed for their clinical control and exacerbation rate in the year prior to and time on mepolizumab. No human investigation required IRB approval Results: There were 16 patients, 6 male,10 female,10 Caucasian and 6 non-Caucasian, age range 29-73 years, mean 58 years, median 52 years with moderate to severe asthma (range FEVI 21%->100% mean65%/median 66%) years of asthma 3year-50years mean 30year, median 30 years, eosinophils/mm#3 range 154-573 median 240/ mm#3 mean 266/mm#3 on mepolizumab for a mean16.5 /median 17.5 range 1months to 27 months .There was a range 0-12, median 6, mean 5.6 of exacerbations in the year prior and year on mepolizumab range 0-6,mean 1.5 median 0. With decline or reduction in exacerbations by 73% from 90 to 24 over 1 year or from 5.6/person to 1.5 per person with<0.1 p>0.05 not significant. Conclusions: The results or outcomes suggest that mepolizumab is an effective therapy for asthma in moderate to severe asthma added to optimal inhaled and oral therapy reducing exacerbations and providing better asthma control though the reduction rate was 73% not meeting significance though the rate in the literature is 80% reduction with p value<0.05.
P202 Asthma, Other Lower Airway Disorders
P200 T CELL-INDUCED BRONCHOCONSTRICTION IN MICE A. MORI*, Sagamihara, Kanagawa, Japan Introduction: To investigate a role of helper T (Th) cells in asthma, T cell-transfer model was analyzed for late phase asthmatic responses. Methods: Ovalbumin (OVA) specific Th clones were derived from splenocytes of DO11.10 transgenic mice expressing T cell receptor specific for OVA/H-2d. Th clones were adoptively transferred into unprimed mice. After intranasal or inhalation challenge with OVA, airway resistance was continuously monitored by either unrestrained whole body plethysmography (BUXCO) or resistance/compliance analyzer under anesthetized condition. Supernatants of stimulated Th clones were analyzed for contractile activity using collagen gels embedded with murine primary bronchial smooth muscle cells. Effects of H1R and LTR1 antagonist were analyzed both in vitro and in vivo. Results: When unprimed mice were transferred with Th clones, T5-1, T6-2, T6-4, and T6-7, Penh values were significantly increased 6 hr after OVA challenge. In contrast, mice transferred with other Th clones, BF7, T6-1, or T6-10 did not show any change. Airflow limitation was confirmed by a direct measurement of airway resistance under anesthetized, restrained, and intubated conditions. The airflow limitation was also efficiently induced by the challenge with T cell epitope peptide, OVA323-339. Contractile activity was detected in the supernatants of T6-2 stimulated with immobilized anti-CD3. T cell-induced contraction was not affected by H1R or LTR1 antagonist. Conclusions: Activation of Th cells resulted in an airflow limitation besides eosinophilic inflammation, AHR, and mucous hyperplasia.
EVALUATION OF THE ASSOCIATION BETWEEN ASTHMA CONTROL AND TREATMENT STEP IN A REAL-WORLD ANALYSIS A. Fuhlbrigge*,1, V. Ghushchyan2, J. Marvel3, Y. Barrett3, P. Sullivan2, 1. Aurora, CO; 2. Denver, CO; 3. East Hanover, NJ Introduction: The Expert Panel Report-3 (EPR-3) guideline recommends a stepwise approach to attain asthma control. We examined the association between asthma control and EPR-3 step in a managed-care population with asthma. Methods: Retrospective analysis of patient survey responses from the Observational Study of Asthma Control and Outcomes. Eligible patients with persistent asthma aged ≥ 12 years received 4 identical surveys (Waves [W]1−4), which included the 5-item Asthma Control Questionnaire (ACQ-5), over 15 months. Unadjusted mean ACQ-5 scores were compared across EPR-3 steps (S)2−6 (S1 results excluded due to group heterogeneity). Adjusted regression analyses (§ baseline-controlled [W1 ACQ-5 score]) were conducted for W2 only (reference category: S2). Results: Mean (SD) ACQ-5 scores were higher/worse for patients in higher EPR-3 steps: S2(n=994), 0.84(0.79); S3(n=1314), 0.87(0.77); S4 (n=1138), 1.03(0.90); S5(n=937), 1.11(0.91); S6(n=79), 1.50(1.21). Similarly, in regression analyses uncontrolled for baseline, ACQ-5 scores were statistically significantly worse in higher EPR-3 steps (S4−S6) vs S2 (Table) (R2=0.13). Statistical significance did not persist in baselinecontrolled analyses, and for each one-point increase in baseline ACQ-5 score, W2 score was 0.61 points higher (Table). This result, in addition to significantly higher R2 (R2=0.45), suggests that baseline ACQ-5 score is more predictive of future scores than EPR-3 step categorization. Conclusions: A statistically significant relationship was observed between ACQ-5 score and EPR-3 S4−6. However, baseline ACQ-5
S38
T cell-derived bronchoconstrictor might be a target for treatmentresistant asthma.
P171 LANADELUMAB EFFICACY AFTER SWITCHING FROM PLACEBO: RESULTS FROM THE HELP AND HELP OPEN-LABEL EXTENSION STUDIES R. Tachdjian*,1, J. Anderson2, P. Busse3, D. Johnston4, S. Kiani5, C. Nurse6, K. Paes6, 1. Santa Monica, CA; 2. Birmingham, AL; 3. New York, NY; 4. Charlotte, NC; 5. London, United Kingdom; 6. Lexington, MA Introduction: Lanadelumab significantly reduced hereditary angioedema (HAE) attack rates versus placebo over 26 weeks in the phase 3 double-blind (DB) HELP Study (NCT02586805). Patients who completed the DB continued into the ongoing open-label extension study (OLE; NCT02741596). This interim analysis of data from 26May201601Sept2017 evaluated lanadelumab efficacy in the OLE among patients who received placebo in the DB. Methods: Patients from the DB placebo group received a single 300 mg lanadelumab dose on Day 1 of the OLE. Following their first attack, they received lanadelumab 300 mg every 2 weeks. Results: 33 patients from the DB placebo group entered the OLE. Their median time on study in the OLE was 8.6 months (range 6.6-12.6 months); all patients completed ≥ 6 months’ time on study, and 14 (42.4%) patients completed ≥ 9 months. During the DB run-in and treatment periods, patients had a median attack rate of 2.90 and 1.82 attacks/month, respectively (Figure). During the OLE, the median attack rate was 0.10 attacks/month. The median change in attack rate between the DB and OLE treatment periods was ¡1.38 attacks/month (¡98.5%). Conclusions: Consistent with the DB results, there was a significant reduction in attack rate with lanadelumab treatment among patients who previously received placebo. Attack rates in the DB and OLE studies
P201 PRIVATE PRACTICE EXPERIENCE WITH MEPOLIZUMAB THERAPY C. Randolph*, SOUTHBURY, CT Introduction: Mepolizumab or anti-IL-5 is a therapeutic agent recently approved for intractable moderate to severe asthma despite optimal oral and inhaled therapy. It has been demonstrated to diminish asthma exacerbations. It is administered monthly 100mg subcutaneously as a single dose. We review our experience with 16 patients with moderate to severe asthma over a 1-2 year period. Methods: Patients with moderate to severe asthma in a currently two provider allergy /immunology private practice initiated on mepolizumab over a 1-2 year period were followed for their clinical control and exacerbation rate in the year prior to and time on mepolizumab. No human investigation required IRB approval Results: There were 16 patients, 6 male,10 female,10 Caucasian and 6 non-Caucasian, age range 29-73 years, mean 58 years, median 52 years with moderate to severe asthma (range FEVI 21%->100% mean65%/median 66%) years of asthma 3year-50years mean 30year, median 30 years, eosinophils/mm#3 range 154-573 median 240/ mm#3 mean 266/mm#3 on mepolizumab for a mean16.5 /median 17.5 range 1months to 27 months .There was a range 0-12, median 6, mean 5.6 of exacerbations in the year prior and year on mepolizumab range 0-6,mean 1.5 median 0. With decline or reduction in exacerbations by 73% from 90 to 24 over 1 year or from 5.6/person to 1.5 per person with<0.1 p>0.05 not significant. Conclusions: The results or outcomes suggest that mepolizumab is an effective therapy for asthma in moderate to severe asthma added to optimal inhaled and oral therapy reducing exacerbations and providing better asthma control though the reduction rate was 73% not meeting significance though the rate in the literature is 80% reduction with p value<0.05.
P202 Asthma, Other Lower Airway Disorders
P200 T CELL-INDUCED BRONCHOCONSTRICTION IN MICE A. MORI*, Sagamihara, Kanagawa, Japan Introduction: To investigate a role of helper T (Th) cells in asthma, T cell-transfer model was analyzed for late phase asthmatic responses. Methods: Ovalbumin (OVA) specific Th clones were derived from splenocytes of DO11.10 transgenic mice expressing T cell receptor specific for OVA/H-2d. Th clones were adoptively transferred into unprimed mice. After intranasal or inhalation challenge with OVA, airway resistance was continuously monitored by either unrestrained whole body plethysmography (BUXCO) or resistance/compliance analyzer under anesthetized condition. Supernatants of stimulated Th clones were analyzed for contractile activity using collagen gels embedded with murine primary bronchial smooth muscle cells. Effects of H1R and LTR1 antagonist were analyzed both in vitro and in vivo. Results: When unprimed mice were transferred with Th clones, T5-1, T6-2, T6-4, and T6-7, Penh values were significantly increased 6 hr after OVA challenge. In contrast, mice transferred with other Th clones, BF7, T6-1, or T6-10 did not show any change. Airflow limitation was confirmed by a direct measurement of airway resistance under anesthetized, restrained, and intubated conditions. The airflow limitation was also efficiently induced by the challenge with T cell epitope peptide, OVA323-339. Contractile activity was detected in the supernatants of T6-2 stimulated with immobilized anti-CD3. T cell-induced contraction was not affected by H1R or LTR1 antagonist. Conclusions: Activation of Th cells resulted in an airflow limitation besides eosinophilic inflammation, AHR, and mucous hyperplasia.
EVALUATION OF THE ASSOCIATION BETWEEN ASTHMA CONTROL AND TREATMENT STEP IN A REAL-WORLD ANALYSIS A. Fuhlbrigge*,1, V. Ghushchyan2, J. Marvel3, Y. Barrett3, P. Sullivan2, 1. Aurora, CO; 2. Denver, CO; 3. East Hanover, NJ Introduction: The Expert Panel Report-3 (EPR-3) guideline recommends a stepwise approach to attain asthma control. We examined the association between asthma control and EPR-3 step in a managed-care population with asthma. Methods: Retrospective analysis of patient survey responses from the Observational Study of Asthma Control and Outcomes. Eligible patients with persistent asthma aged ≥ 12 years received 4 identical surveys (Waves [W]1−4), which included the 5-item Asthma Control Questionnaire (ACQ-5), over 15 months. Unadjusted mean ACQ-5 scores were compared across EPR-3 steps (S)2−6 (S1 results excluded due to group heterogeneity). Adjusted regression analyses (§ baseline-controlled [W1 ACQ-5 score]) were conducted for W2 only (reference category: S2). Results: Mean (SD) ACQ-5 scores were higher/worse for patients in higher EPR-3 steps: S2(n=994), 0.84(0.79); S3(n=1314), 0.87(0.77); S4 (n=1138), 1.03(0.90); S5(n=937), 1.11(0.91); S6(n=79), 1.50(1.21). Similarly, in regression analyses uncontrolled for baseline, ACQ-5 scores were statistically significantly worse in higher EPR-3 steps (S4−S6) vs S2 (Table) (R2=0.13). Statistical significance did not persist in baselinecontrolled analyses, and for each one-point increase in baseline ACQ-5 score, W2 score was 0.61 points higher (Table). This result, in addition to significantly higher R2 (R2=0.45), suggests that baseline ACQ-5 score is more predictive of future scores than EPR-3 step categorization. Conclusions: A statistically significant relationship was observed between ACQ-5 score and EPR-3 S4−6. However, baseline ACQ-5