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Correct and incorrect dosing of proton pump inhibitors and its impact on GERD symptoms
S1592
correct dosing should result in better control of GERD symptoms, this hypothesis has not been evaluated in a large population, Aims: To assess the effect of PPI dosing on GERD symptoms. Methods: 638 patients from a local HMO newly prescribed a PP[ for GERD were identified using pharmacy claims data. Utilizing focused study questions as well as the validated Quality of Life in Reflux Associated Disease questionnaire (QOLRAD), participants were surveyed on their dosing habits and GERD symptoms. Participants were considered optimal dosers if they took their PPI within 15-60 minutes of the first meal of the day, correct closers took their PPIs with meals to up to 60 minutes before any meal. Incorrect dosers took their PPls greater than 60 minutes before meals, after meals, as needed, or at bedtime. The QOLRAD was scored from 1-7 and symptom severity were defined as severe (<5) and moderate to no symptoms (>5). Results: 625 subjects were contacted and 173 subjects participated in the study. No differences were identified between participants and nonparticipants based on age, gender, or formulation of PPI prescribed. At baseline 27.1% of participants dosed their PPl correctly and only 9.7% dosed their PPI optimally. Mean scores for correct and incorrect dosers were 5.51 and 5.82 respectively (p = 0.18). Symptom scores based on emotional distress, sleep disturbance, problems associated with food/drink, daily function and vitality were hkewise examined. Patients with severe GERD were more likely to be incorrect dosers, however, these results were not statistically significant. Conclusion: Only 27% of newly prescribed a PP1 for GERD dosed correctly and 9.7% dosed optimally. GERD symptoms were not affected by PPI dosing behavior This phenomenon may reflect either a lack of true GERD symptoms in this population or demonstrate that correct dosing of a PP1 is not important to achieve a clinical benefit. Patients reporting severe symptoms, however, were more likely to report incorrect dosing suggesting that in this subset of patients, uncontrolled GERD may be attributable to dosing habits. Studies assessing the clinical impact of PP[ dosing on a population with severe GERD are underway.
Two Weeks of Rabeprazole (RAB) Treatment Is as Effective as 4 Weeks for Relieving Symptoms of Gastroesophageal Reflux Disease (GERD) Arsene Papazian, Stanisfas Bruley Des Varannes, Jacques Corallo, Philippe Houcke, JeanPaul Jacques, Patrick Levy',Jean-Francois Rey, Fernand Vicari, Elizabeth Tocque, Sylvie 8onnot-Marlier Aim: To compare the efficacy of 2 weeks versus 4 weeks of RAB treatment for the relief of GERD in patients with mild-to-moderate esophagitis. Methods: Patients aged 18 years and older with GERD symptoms and mild-to-moderate esophagitis who had received -<1 antisecretory or prokinetic treatment course during the past 6 months were randomized to 2 groups: group 1 received RAB 20 mg qd for 14 days, followed by placebo qd for 14 days; group 2 received RAB 20 qd for 28 days. Symptoms were rated on the DeMeester and Johnson scale (0 to 10), evaluating the intensity, frequency, occurrence, and duration of symptoms. Enrolled patients had a score :>6 for their predominant symptom. Therapeutic success was defined as a score -<4. Heartburn and acid regurgitation were evaluated on days 0, 7, 14, and 28. The primary endpoint was the change in symptom score between day 0 and the last visit on treatment (day 14, group l ; day 28, group 2). Statistical equivalence was defined as the upper bound of the 95% confidence interval (CI) for the difference between the 2 groups < 1. Results: Of the intern-to-treat population (N = 260; 55% men; mean age, 48 yr), 73% were diagnosed with grade I esophagins (Savary-Moniner) and 27% with grade 2. No significant difference in change of symptom score was seen between groups 1 and 2 at treatment endpoint (6.93 vs 6.49, respectively; upper bound of CI=0.063) (table). Furthermore, there was no difference between the 2 groups in therapeutic success: 91.2% at day 14 (group 1) and 89.3% at day 28 (group 2) (p = 0.62). Only 9 patients discontinued the study due to adverse events (5, group 1; 4, group 2) Conclusions: Two weeks of RAB 20-rag treatment is as effective as 4 weeks' RAB 20-rag treatment for GERD symptom relief in patients with mild-to-moderate esophagitis, thereby demonstrating a significantly faster onset of symptom resolution compared with the standard treatment length. Research supported
S1595 The Use of Sertraline for the Treatment of Gastroesophageal Reflux Disease and Resistant Dyspepsia Greg L Clary, John B. O'Connor, Marilyn Schanche, K. Ranga Rama Krishnan
by janssen-Cilag, Issv-Les-Moufineaux, F~ance Mean Symptom Score (_+StandardDeviation) Group 1, Day 14 Baseline Score 8.07 (0.94) Endpoint Score* 1.14 (2.26) Variation (Ba,,eline-Endpoint) 6.93 (2.35) *Last visiton activetreatmentday 14 for group1; day 28 for group2.
While proton pump inhibitors (PPI) and H2 blockers remain the mainstay of treatment for gastroesophegeal reflux disease (GERD) often more than 50% of patients with typical GERD symptoms have no esophageal erosions at endoscopy (EGD) and their symptoms may remain refractory to pharmacologic intervention. Previously it has been reported that the seromonin selective reuptake inhibitor (SSRI) sertraline was effective in the treatment of non-cardiac chest pain, which lead us to query its use in GERD. Our study was a 12-week double-bhnd randomized clinical trial of sertraline versus placebo in GERD. Inclusion criteria required the presence of chronic heartburn + A regurgitation and negative EGD, and exclusion criteria included the absence of depressive illness as demonstarted by the Hamilton Depression Scale. Our study also included a 2-week washout period for all PPI's and H2 blockers prior to initiation of treatment. Our results demonstrated improvements of Severity of Symptoms (1.91 vs 2.18, p=0.0712) and Global Improvement (3.27 vs 3.91, p= 0.064) in the 22 patients examined to date. Recruitment in our study continues, but this preliminary data suggests that the SSRI's may offer a true treatment effect for the symptoms of non-erosive GERD and dyspepsia without concurrent use of either PPI's or H2 blockers
Group 2, Day 28 8.03 (*0.92) 1.54 (~2.51) 6.49 (2.59)
S1593
Comparative Effects of an Omeprazole Antacid Complex-Immediate Release (OAC-IR) and Omeprazole-Delayed Release (OME-DR) on Omeprazole Pharmacokinetics (PK) and Gastric pH in Healthy Subjects Bonnie Hepburn, Barry Goldhist Introduction. ()ME is currently administered in enteric-coated (DR) granules to prevent degradation of OME by gasmc acid. It inhibits gastric acid secretion for 24 hours, but cannot prowde immediate rdief of existing heartburn. OAC-IR, however, might be effective treatment for existing and recurrent heartburn. The antacid could produce immediate relief of symptoms and also protect OME from degradation by gastric acid Aim. To compare OAC-IR and OME-DR with regard to PK and gastric pH Methods. In a crossover trial, l0 fasting subjects received a singlq 40rag OME-DR capsule and 7 received 40mg OME powder plus a chewable tablet composed of 1260rag NaHCO~ and 750rag CaCO~. Plasma OME was measured over a 6-hour postdose period. Gastnc pH was measured for 1 hour before and 6 hours after dosing. Resuhs. OME absorption from OAC-IR was more rapid (Tmax 25 rain; Cmax 1019ng/ mL) than from the OME-DR fornmlation (Tmax 127 min; Cmax 544ng/mL). Bioavailability of OAC-IR (AUC~,,,~ 1120nghr/mL) and OME-DR (AUCo,,,~ ll70ng.hr/mL) were similar ( P - 0 9 6 ) . Integrated gastric acidity over the 6-hour postdose period was 43% less with OAC-IR than with OM E-DR (P .526; median for all subjects). Conclusions. When compared to a marketed DR formulation, OAC-IR has more rapid absorption, with similar bioavailability and pharmacodynamic eftect OAC-IR should be particularly effective in relieving heartburn, with the antacid producing immediate relief and OME preventing recurrence of subsequent episodes. P~Nc.mc~kir~4tco of ~
$1596 Fast and Complete Control of Heartburn in On-Demand Rabeprazole (RAB) Maintenance Therapy in Patients with Nonerosive Reflux Disease (NERD) Peter Bytzer, Andre L Bhim, Dirk De Herdt Background: In previous placebo (PBO)-controlled studies of daily therapy in NERD patients, RAB resulted in a significantly faster time to first heartburn-free interval. Aim: To deterrmne the time to achieve heartburn control with RAB taken on demand in a long-term maintenance trial in NERD patients. Methods: 535 patients with endoscopy-confirmed NERD with moderate to very severe heartburn were enrolled in a 4-week, open-label, acute-phase trial of RAB 10 rag/day. Patients scored heartburn severity at baseline and week 4 for the preceding 7 days on a 5-point Likert scale (0=no problem; 4=very severe problem), and heartburn frequency for the same time periods (0=no heartburn; 1 = 1-2 days/wk; 2=2-4 days/wk; 3 = 5-6 days/wk; 4 = 7 days/wk). Patients free of heartburn were randomized to doubleblind treatment with RAB 10 rag/day or PBO on-demand for 6 months. Subjects took 1 tablet/day when they experienced heartburn and stopped taking the medication only after experiencing symptom relief for a full 24-h period. Results: 450 patients (84%) taking RAB in the acute phase reported complete heartburn relief after 4 weeks; 418 were randomized in the on-demand, maintenance phase. During acute treatment with RAB, mean heartburn severity score decreased from 2.4 ( -+0.02) to 0.3 ( -+0.03) (p<0.0001), and mean heartburn frequency score decreased from 2.9 (_+0.04) to 0.4 (_+0.04) (p<0.0001). During the ondemand treatment phase, average RAB use was 1 tablet every 4 days. The percentage of patients taking study medication for only 1-2 consecutive days during any relapse period was 27% for RAB versus 16% for PBO. In addition, 56% of patients in the RAB group took the study drug for at most 4 consecutive days at any time versus 42% for PBO. Furthermore, antacid use was 2-fold higher in the PBO group (p = 0.0009). Conclusion: This study demonstrated that fast and complete heartburn relief, accompanied by reduced antacid use, is achieved with brief periods of on-demand rabeprazole 10-mg maintenance therapy in NERD patients. Research supported by Janssen-Cilag, a division of Janssen Pharmaceutica N.V.,
G~e~l~e4e F~ll~4qJ~4
Beerse, Bel~um. S1594
S1597
Correct and Incorrect Dosing of Proton Pump Inhibitors and Its Impact on GERD Symptoms Jonathan P Pezanoski, Naresh T Gunaramam, Mark Cowen
"Omeprazole-Gastrin Test" - - a Reliable Predictor for CYP-2CI9 Phenotype Etsuo Hoshino, Makoto Tatewaki, Hideto Motegi, Takahara Ohbayashi, Tohrn Ohse
Background: Proton pump inhibitors (PPIs) are most effective in inhibiting acid secretion when dosed up to an hour before a meal. We have previously observed that PPIs are incorrectly dosed in over 50% of patients(Gastroemerology 2001:120: A2205). Although
BACKGROUND/AlMS: Clinical effect of omeprazole (OPZ) is not constant due to genetic polymorphism of cytochrome P450 (CYP)-2C19, because the greater part of OPZ has been reported to be metabolized by CYP-2C19. Thus, OPZ is more effective for poor metabolizers
AGA Abstracts
A-228
correct dosing should result in better control of GERD symptoms, this hypothesis has not been evaluated in a large population, Aims: To assess the effect of PPI dosing on GERD symptoms. Methods: 638 patients from a local HMO newly prescribed a PP[ for GERD were identified using pharmacy claims data. Utilizing focused study questions as well as the validated Quality of Life in Reflux Associated Disease questionnaire (QOLRAD), participants were surveyed on their dosing habits and GERD symptoms. Participants were considered optimal dosers if they took their PPI within 15-60 minutes of the first meal of the day, correct closers took their PPIs with meals to up to 60 minutes before any meal. Incorrect dosers took their PPls greater than 60 minutes before meals, after meals, as needed, or at bedtime. The QOLRAD was scored from 1-7 and symptom severity were defined as severe (<5) and moderate to no symptoms (>5). Results: 625 subjects were contacted and 173 subjects participated in the study. No differences were identified between participants and nonparticipants based on age, gender, or formulation of PPI prescribed. At baseline 27.1% of participants dosed their PPl correctly and only 9.7% dosed their PPI optimally. Mean scores for correct and incorrect dosers were 5.51 and 5.82 respectively (p = 0.18). Symptom scores based on emotional distress, sleep disturbance, problems associated with food/drink, daily function and vitality were hkewise examined. Patients with severe GERD were more likely to be incorrect dosers, however, these results were not statistically significant. Conclusion: Only 27% of newly prescribed a PP1 for GERD dosed correctly and 9.7% dosed optimally. GERD symptoms were not affected by PPI dosing behavior This phenomenon may reflect either a lack of true GERD symptoms in this population or demonstrate that correct dosing of a PP1 is not important to achieve a clinical benefit. Patients reporting severe symptoms, however, were more likely to report incorrect dosing suggesting that in this subset of patients, uncontrolled GERD may be attributable to dosing habits. Studies assessing the clinical impact of PP[ dosing on a population with severe GERD are underway.
Two Weeks of Rabeprazole (RAB) Treatment Is as Effective as 4 Weeks for Relieving Symptoms of Gastroesophageal Reflux Disease (GERD) Arsene Papazian, Stanisfas Bruley Des Varannes, Jacques Corallo, Philippe Houcke, JeanPaul Jacques, Patrick Levy',Jean-Francois Rey, Fernand Vicari, Elizabeth Tocque, Sylvie 8onnot-Marlier Aim: To compare the efficacy of 2 weeks versus 4 weeks of RAB treatment for the relief of GERD in patients with mild-to-moderate esophagitis. Methods: Patients aged 18 years and older with GERD symptoms and mild-to-moderate esophagitis who had received -<1 antisecretory or prokinetic treatment course during the past 6 months were randomized to 2 groups: group 1 received RAB 20 mg qd for 14 days, followed by placebo qd for 14 days; group 2 received RAB 20 qd for 28 days. Symptoms were rated on the DeMeester and Johnson scale (0 to 10), evaluating the intensity, frequency, occurrence, and duration of symptoms. Enrolled patients had a score :>6 for their predominant symptom. Therapeutic success was defined as a score -<4. Heartburn and acid regurgitation were evaluated on days 0, 7, 14, and 28. The primary endpoint was the change in symptom score between day 0 and the last visit on treatment (day 14, group l ; day 28, group 2). Statistical equivalence was defined as the upper bound of the 95% confidence interval (CI) for the difference between the 2 groups < 1. Results: Of the intern-to-treat population (N = 260; 55% men; mean age, 48 yr), 73% were diagnosed with grade I esophagins (Savary-Moniner) and 27% with grade 2. No significant difference in change of symptom score was seen between groups 1 and 2 at treatment endpoint (6.93 vs 6.49, respectively; upper bound of CI=0.063) (table). Furthermore, there was no difference between the 2 groups in therapeutic success: 91.2% at day 14 (group 1) and 89.3% at day 28 (group 2) (p = 0.62). Only 9 patients discontinued the study due to adverse events (5, group 1; 4, group 2) Conclusions: Two weeks of RAB 20-rag treatment is as effective as 4 weeks' RAB 20-rag treatment for GERD symptom relief in patients with mild-to-moderate esophagitis, thereby demonstrating a significantly faster onset of symptom resolution compared with the standard treatment length. Research supported
S1595 The Use of Sertraline for the Treatment of Gastroesophageal Reflux Disease and Resistant Dyspepsia Greg L Clary, John B. O'Connor, Marilyn Schanche, K. Ranga Rama Krishnan
by janssen-Cilag, Issv-Les-Moufineaux, F~ance Mean Symptom Score (_+StandardDeviation) Group 1, Day 14 Baseline Score 8.07 (0.94) Endpoint Score* 1.14 (2.26) Variation (Ba,,eline-Endpoint) 6.93 (2.35) *Last visiton activetreatmentday 14 for group1; day 28 for group2.
While proton pump inhibitors (PPI) and H2 blockers remain the mainstay of treatment for gastroesophegeal reflux disease (GERD) often more than 50% of patients with typical GERD symptoms have no esophageal erosions at endoscopy (EGD) and their symptoms may remain refractory to pharmacologic intervention. Previously it has been reported that the seromonin selective reuptake inhibitor (SSRI) sertraline was effective in the treatment of non-cardiac chest pain, which lead us to query its use in GERD. Our study was a 12-week double-bhnd randomized clinical trial of sertraline versus placebo in GERD. Inclusion criteria required the presence of chronic heartburn + A regurgitation and negative EGD, and exclusion criteria included the absence of depressive illness as demonstarted by the Hamilton Depression Scale. Our study also included a 2-week washout period for all PPI's and H2 blockers prior to initiation of treatment. Our results demonstrated improvements of Severity of Symptoms (1.91 vs 2.18, p=0.0712) and Global Improvement (3.27 vs 3.91, p= 0.064) in the 22 patients examined to date. Recruitment in our study continues, but this preliminary data suggests that the SSRI's may offer a true treatment effect for the symptoms of non-erosive GERD and dyspepsia without concurrent use of either PPI's or H2 blockers
Group 2, Day 28 8.03 (*0.92) 1.54 (~2.51) 6.49 (2.59)
S1593
Comparative Effects of an Omeprazole Antacid Complex-Immediate Release (OAC-IR) and Omeprazole-Delayed Release (OME-DR) on Omeprazole Pharmacokinetics (PK) and Gastric pH in Healthy Subjects Bonnie Hepburn, Barry Goldhist Introduction. ()ME is currently administered in enteric-coated (DR) granules to prevent degradation of OME by gasmc acid. It inhibits gastric acid secretion for 24 hours, but cannot prowde immediate rdief of existing heartburn. OAC-IR, however, might be effective treatment for existing and recurrent heartburn. The antacid could produce immediate relief of symptoms and also protect OME from degradation by gastric acid Aim. To compare OAC-IR and OME-DR with regard to PK and gastric pH Methods. In a crossover trial, l0 fasting subjects received a singlq 40rag OME-DR capsule and 7 received 40mg OME powder plus a chewable tablet composed of 1260rag NaHCO~ and 750rag CaCO~. Plasma OME was measured over a 6-hour postdose period. Gastnc pH was measured for 1 hour before and 6 hours after dosing. Resuhs. OME absorption from OAC-IR was more rapid (Tmax 25 rain; Cmax 1019ng/ mL) than from the OME-DR fornmlation (Tmax 127 min; Cmax 544ng/mL). Bioavailability of OAC-IR (AUC~,,,~ 1120nghr/mL) and OME-DR (AUCo,,,~ ll70ng.hr/mL) were similar ( P - 0 9 6 ) . Integrated gastric acidity over the 6-hour postdose period was 43% less with OAC-IR than with OM E-DR (P .526; median for all subjects). Conclusions. When compared to a marketed DR formulation, OAC-IR has more rapid absorption, with similar bioavailability and pharmacodynamic eftect OAC-IR should be particularly effective in relieving heartburn, with the antacid producing immediate relief and OME preventing recurrence of subsequent episodes. P~Nc.mc~kir~4tco of ~
$1596 Fast and Complete Control of Heartburn in On-Demand Rabeprazole (RAB) Maintenance Therapy in Patients with Nonerosive Reflux Disease (NERD) Peter Bytzer, Andre L Bhim, Dirk De Herdt Background: In previous placebo (PBO)-controlled studies of daily therapy in NERD patients, RAB resulted in a significantly faster time to first heartburn-free interval. Aim: To deterrmne the time to achieve heartburn control with RAB taken on demand in a long-term maintenance trial in NERD patients. Methods: 535 patients with endoscopy-confirmed NERD with moderate to very severe heartburn were enrolled in a 4-week, open-label, acute-phase trial of RAB 10 rag/day. Patients scored heartburn severity at baseline and week 4 for the preceding 7 days on a 5-point Likert scale (0=no problem; 4=very severe problem), and heartburn frequency for the same time periods (0=no heartburn; 1 = 1-2 days/wk; 2=2-4 days/wk; 3 = 5-6 days/wk; 4 = 7 days/wk). Patients free of heartburn were randomized to doubleblind treatment with RAB 10 rag/day or PBO on-demand for 6 months. Subjects took 1 tablet/day when they experienced heartburn and stopped taking the medication only after experiencing symptom relief for a full 24-h period. Results: 450 patients (84%) taking RAB in the acute phase reported complete heartburn relief after 4 weeks; 418 were randomized in the on-demand, maintenance phase. During acute treatment with RAB, mean heartburn severity score decreased from 2.4 ( -+0.02) to 0.3 ( -+0.03) (p<0.0001), and mean heartburn frequency score decreased from 2.9 (_+0.04) to 0.4 (_+0.04) (p<0.0001). During the ondemand treatment phase, average RAB use was 1 tablet every 4 days. The percentage of patients taking study medication for only 1-2 consecutive days during any relapse period was 27% for RAB versus 16% for PBO. In addition, 56% of patients in the RAB group took the study drug for at most 4 consecutive days at any time versus 42% for PBO. Furthermore, antacid use was 2-fold higher in the PBO group (p = 0.0009). Conclusion: This study demonstrated that fast and complete heartburn relief, accompanied by reduced antacid use, is achieved with brief periods of on-demand rabeprazole 10-mg maintenance therapy in NERD patients. Research supported by Janssen-Cilag, a division of Janssen Pharmaceutica N.V.,
G~e~l~e4e F~ll~4qJ~4
Beerse, Bel~um. S1594
S1597
Correct and Incorrect Dosing of Proton Pump Inhibitors and Its Impact on GERD Symptoms Jonathan P Pezanoski, Naresh T Gunaramam, Mark Cowen
"Omeprazole-Gastrin Test" - - a Reliable Predictor for CYP-2CI9 Phenotype Etsuo Hoshino, Makoto Tatewaki, Hideto Motegi, Takahara Ohbayashi, Tohrn Ohse
Background: Proton pump inhibitors (PPIs) are most effective in inhibiting acid secretion when dosed up to an hour before a meal. We have previously observed that PPIs are incorrectly dosed in over 50% of patients(Gastroemerology 2001:120: A2205). Although
BACKGROUND/AlMS: Clinical effect of omeprazole (OPZ) is not constant due to genetic polymorphism of cytochrome P450 (CYP)-2C19, because the greater part of OPZ has been reported to be metabolized by CYP-2C19. Thus, OPZ is more effective for poor metabolizers
AGA Abstracts
A-228