Post-marketing Observational Study Research Articles

Safety and Efficacy of Almagate and Simethicone Combination in Symptomatic Management of GERD: Post-marketing Observational TRIALMA Study

Safety and Efficacy of Almagate and Simethicone Combination in Symptomatic Management of GERD: Post-marketing Observational TRIALMA Study

The implementation of rifapentine and isoniazid (3HP) in two remote Arctic communities with a predominantly Inuit population, the Taima TB 3HP study

ABSTRACT Background: The incidence of TB among Inuit is the highest in Canada. A significantly shorter latent TB infection (LTBI) treatment with rifapentine and isoniazid once weekly for 12 weeks (3HP) is now available in limited settings in Canada. Methods: A prospective open-label 2-year observational postmarketing study was conducted introducing 3HP for the first time in Canada in Iqaluit followed by a program rollout in Qikiqtarjuaq, Nunavut. Results: A total of 247 people were offered 3HP, 102 in the Iqaluit postmarketing study and 145 in the Qikiqtarjuaq program roll out. Although statistical significance was not reached, more people who started treatment completed treatment in the 3HP group (Iqaluit, 60/73 (82.2%) and Qikiqtarjuaq, 89/115 (77.4%)) than in the historical control 9INHgroup (306/420 = 72.9%) (p = 0.2). Most of the adverse events in 3HP treated patients were associated with mild discomfort but no disruption of normal daily activity. Not drinking alcohol was associated with increased 3HP completion (OR 13.33, 95% CI, 2.27–78.20) as was not taking concomitant medications (OR 7.19, 95% CI, 1.47–35.30). Conclusions: The present study supports the feasibility and safety profile of 3HP for the treatment of LTBI in Nunavut.

Abatacept in rheumatoid arthritis and the risk of cancer: a world observational post-marketing study.

We aimed to investigate whether abatacept used in patients for RA was associated with an increased risk of reporting overall cancer and specific cancers, including breast, lung, lymphoma, melanoma and non-melanoma skin cancer when compared with other biologic DMARDs (bDMARDs). We performed an observational study within VigiBase, the World Health Organization's global database of individual case safety reports, from 2007 to 2017 to compare the cases of cancer reported in RA patients exposed to abatacept with those reported in RA patients exposed to other bDMARDs. We conducted disproportionality analyses allowing the estimation of reporting odds ratios (RORs) with 95% CIs of the exposure odds among spontaneous reporting of cancers to the exposure odds among other reported adverse effects. We identified 15846 adverse effects reported in RA patients who received abatacept and 290568 adverse effects reported in RA patients treated with other bDMARDs. Compared with other bDMARDs, the use of abatacept was not associated with an increased risk of reporting cancer overall [ROR 0.98 (95% CI 0.91, 1.05)]. Analyses by specific cancer sites showed a significantly increased ROR for melanoma [1.58 (95% CI 1.17, 2.08)], but not for other specific cancer sites. Compared with other bDMARDs, exposure to abatacept in RA patients was only significantly associated with an increased risk of reporting melanoma. This increased risk is consistent with the properties of abatacept (CTLA-4 agonist) since it has an opposite action than ipilimumab, an antibody that blocks CTLA-4 and is approved for the treatment of malignant melanoma. ClinicalTrials.gov (http://clinicaltrials.gov), NCT03980639.

Prasugrel for Japanese Patients With Ischemic Heart Disease in Long-Term Clinical Practice (PRASFIT-Practice II) - 1-Year Follow-up Results of a Postmarketing Observational Study.

Although the effectiveness and safety of prasugrel for the prevention of cardiovascular events in patients with ischemic heart disease (IHD) undergoing percutaneous coronary intervention (PCI) have been demonstrated, long-term real-world data of Japanese unique doses are insufficient. Therefore, we report the results of an analysis of 1-year follow-up data from a postmarketing observational study (PRASFIT-Practice II).Methods and Results:The safety and effectiveness analysis sets included 4,155 IHD patients receiving prasugrel (loading dose/maintenance dose, 20/3.75 mg) as dual antiplatelet therapy (DAPT) with aspirin. At 360 days (after treatment start), 62.2% continued DAPT. Cumulative incidences of major adverse cardiovascular events and stent thrombosis were 1.6% and 0.2%, respectively. Cumulative incidences of Thrombolysis In Myocardial Infarction (TIMI) major bleeding and TIMI major or minor bleeding were 1.0% and 2.0%, respectively. Risk factors for TIMI major or minor bleeding in the first 30 days of treatment were age ≥80 years, anemia, female sex, and liver disease, and from day 31 to the end of month 12, hypertension and peptic ulcer. The 1-year follow-up results showed long-term effectiveness and safety of prasugrel at dosages approved in Japan for the treatment of IHD patients undergoing PCI.

Safety and Efficacy of Fibrinogen Concentrate in Congenital Fibrinogen Deficiency: A Post-Marketing Observational Study

Background: Congenital fibrinogen deficiencies (CFD), including afibrinogenemia and hypofibrinogenemia, are associated with severe and/or frequent bleeding episodes (BEs) that can occur spontaneously or following trauma. Human fibrinogen concentrate (HFC) has been shown to rapidly restore hemostasis in the event of such bleeding. The safety and efficacy of a new highly purified HFC have been demonstrated in interventional clinical studies; however, real-world evidence collected from routine clinical practice is needed to corroborate these data. Aims: The FORMA-07 study will collect real-world evidence from clinical practice concerning the safety and efficacy of a new HFC in the treatment of CFD. This highly purified, plasma-derived, lyophilized HFC undergoes two dedicated virus inactivation/removal steps during production. Methods: The FORMA-07 study is a post-marketing, multicenter observational study in adults and adolescents (≥12 years) with congenital afibrinogenemia or hypofibrinogenemia who are expected to require on-demand treatment with HFC for BEs. The study will examine treatment with a highly purified, plasma-derived, double virus inactivated/eliminated, lyophilized HFC (Octapharma). This Octapharma-sponsored study will seek approval from independent ethics committees prior to study start. Informed consent will be obtained from all subjects. Exclusion criteria include: other bleeding disorders, including acquired fibrinogen deficiency and dysfibrinogenemia; anti-fibrinogen inhibitors; participation in concurrent clinical studies. The study outline is shown in Figure 1. The primary endpoint is the incidence of thromboembolic adverse drug reactions (ADRs) in patients receiving HFC for on-demand treatment of BEs. Secondary endpoints include the hemostatic efficacy of HFC for treatment of all BEs recorded in the study (with focus on major BEs), assessed by the investigator using a 4-point objective scale within 2-24 hours following treatment. Safety endpoints include ADRs, serious ADRs, and ADRs of special interest (i.e., thromboembolic events and allergic reactions, including anaphylaxis). The planned study duration is up to 6 years and the study aims to enroll a minimum of 25 patients treated with HFC, to describe 105 BEs, including a minimum of 10 major BEs in 10 patients. During the observation period, enrolled patients may be treated for any BEs. Results: Results will be monitored on an ongoing basis and the study is expected to end Q2 2025. Conclusions: This study will collect real-world evidence for the safety and efficacy of HFC during routine clinical use in the treatment of bleeding in patients with congenital fibrinogen deficiency. Figure 1 Disclosures Schwartz: Octapharma: Employment. Peyvandi:Alnylam: Honoraria; Bioverativ: Membership on an entity's Board of Directors or advisory committees; Grifols: Honoraria; Kedrion: Honoraria; Octapharma: Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees. Solomon:Octapharma: Employment. Knaub:Octapharma: Employment. Toth:Octapharma: Employment.

Breast cancer and spironolactone: an observational postmarketing study.

Recent studies have discussed the risk of breast cancer with antihypertensive drugs. For spironolactone, data are conflicting. The present paper investigates this potential signal in VigiBase®, the World Health Organization Global Individual Case Safety Report (ICSR) database. In VigiBase®, we performed a case/non-case study using data registered from 1981 (spironolactone's marketing authorization) to December 31, 2017. Among women ≥ 50years, we measured the risk of reporting "Breast malignant tumors" compared with all other adverse drug reactions (as a crude and adjusted (a) reporting odds ratio (ROR 95% CI)) for spironolactone compared with first, all other drugs and second, pseudo aldosterone antagonists (amiloride, triamterene). ROR were adjusted for age, year of report, continent of report, number of drug prescribed, and completeness score. Sensitivity analyses were performed after exclusion of drug competitors (i.e., drugs like estroprogestative therapy and progestogens that could mask a putative signal) and reports from health professionals. During the study period, 125 ICSRs reported spironolactone exposure and breast malignant cancer in women ≥ 50years. We failed to find a positive association between spironolactone exposure and breast cancer in comparison with exposure to other drugs (aROR = 0.63 95% CI [0.52-0.75]) or pseudo aldosterone antagonists (amiloride, triamterene) (0.56 [0.44-0.72]). Similar trends were found after exclusion of drug competitors and/or reports from health professionals. This study did not find evidence for breast cancer associated with spironolactone.

Real-World Effectiveness and Safety of Fingolimod in Patients With Relapsing Remitting Multiple Sclerosis: A Prospective Analysis in Buenos Aires, Argentina.

The aim of this prospective observational postmarketing study was to evaluate fingolimod effectiveness in a real-world setting in Buenos Aires, Argentina. Relapsing remitting multiple sclerosis patients who had been prescribed fingolimod owing to treatment failure and had at least greater than or equal to 24 months of follow-up were included during August 2013 and June 2018. Three-monthly clinical evaluations and 12-monthly magnetic resonance were performed. Demographic and clinical variables were described as well as the safety and the effectiveness outcomes that included the proportion of patients free from clinical relapses, from disability progression, from new or enlarging T2 or T1 gadolinium-enhancing lesions on annual magnetic resonance imaging, and from any disease activity during the follow-up. A total of 97 patients were included (68% female [n = 66]; mean ± SD age, 30 ± 10.5 years; mean ± SD disease duration, 6.5 ± 3.1 years; mean ± SD Expanded Disability Status Scale, 3.5 ± 1; mean ± SD fingolimod use, 30 ± 13 months [range, 18-56 months]). One hundred percent (97) used previous disease-modifying therapy, mainly interferons (87%; n = 84). Fourteen patients (14.4%) discontinued/withdrew fingolimod (10 owing to disease activity and 4 owing to tolerance and personal decisions). Eighty-two percent were free from clinical relapses, and 85% were free from disability progression; 75% of patients remained free from new or newly enlarging T2 lesions, and 78% of patients were free from gadolinium enhancing lesions. The proportion of patients free from any disease activity was 54%. The effectiveness of fingolimod in a newly real-world setting was consistent with information provided from phase III clinical trials.

Post-marketing observational study of everolimus in patients with unresectable or metastatic renal cell carcinoma in Japan.

To confirm the safety and efficacy of everolimus in patients with unresectable or metastatic RCC. Patients with unresectable or metastatic RCC were included and were followed for up to 1 year from the start of everolimus. The study was conducted at 618 investigational sites in Japan from March 2010 through January 2018. Safety endpoints include adverse events (AEs), and efficacy endpoints were presence/absence of tumor response, progression-free survival (PFS), and overall survival (OS) rate. Of 1694 patients, majority were male (76.33%). Overall, 97.64% of patients experienced AEs and 49% reported serious AEs. The most common serious AEs (incidence of ≥ 5%) include malignant neoplasm progression (21.13%) and interstitial lung disease (10.86%). The incidences of adverse reactions of priority investigation items are as follows: interstitial lung disease (27.74%), infections (11.57%), stomatitis (45.45%), increased in serum creatinine (5.61%), hyperglycemia (14.23%), exacerbation of renal impairment (26.14%), and exacerbation of hepatic impairment (1.15%). The overall tumor response rate was 6.81% with 0.08% CR, and 6.73% PR. The SD was reported in 68.74% of patients. The median PFS was 196 days (95% CI: 181-216 days). The 365-day cumulative OS rate was 82.42%. The acceptable safety and efficacy findings in patients with unresectable or metastatic RCC were confirmed in this study, and are similar to those of pivotal study, which led to the approval, and no new issues were detected. There were no safety or efficacy issues in special populations including elderly and patients with renal/hepatic impairment.

A Post-Marketing Observational Study to Evaluate the Safety and Tolerability of Perampanel as Add-On Therapy in Patients with Epilepsy Aged ≥12 Years (P1.5-024)

A Post-Marketing Observational Study to Evaluate the Safety and Tolerability of Perampanel as Add-On Therapy in Patients with Epilepsy Aged ≥12 Years (P1.5-024)

Real-world treatment of over 1600 Japanese patients with EGFR mutation-positive non-small cell lung cancer with daily afatinib

BackgroundThis prospective, post-marketing observational study in Japanese patients aimed to evaluate the safety and effectiveness of daily afatinib use in general practice.MethodsThis non-interventional study (NCT02131259) enrolled treatment-naïve and pre-treated patients with inoperable/recurrent EGFR mutation-positive NSCLC, eligible for afatinib treatment as per the afatinib label in Japan. Patients received afatinib at the approved dose (20, 30, 40, or 50 mg/day; physician decision), and were observed following treatment initiation for 52 weeks or until premature discontinuation. Primary endpoint was the incidence of adverse drug reactions (ADRs). Secondary endpoints included ADRs of special interest, and objective response rate (ORR). Post hoc Cox multivariate analyses were used to assess prognostic factors associated with the incidence of ADRs.Results1602 patients, at 374 sites (April 2014–March 2015), were included in the analysis; 307 (19%) were aged ≥ 75 years. The most frequently reported ADRs (all/grade 3–4) were diarrhea (78%/15%), rash/acne (59%/6%), stomatitis (31%/4%), and nail effects (38%/4%). Serious ADRs resulting in death occurred in 18 patients (1%). 762 patients (48%) had ≥ 1 afatinib dose reduction and 366 (23%) discontinued due to ADRs; the most common reason for both was diarrhea (8.2% and 6.7%, respectively). ORR was 40.1%.ConclusionsReal-world treatment of 1602 Japanese patients with afatinib was associated with a predictable ADR profile. Afatinib showed effectiveness in inoperable/recurrent EGFR mutation-positive NSCLC, especially as first-line treatment. As with other EGFR TKIs, prompt management of adverse events is needed in the Japanese population, to reduce serious events and outcomes, including interstitial lung disease.

<p>Adherence, satisfaction, and experience with metformin 500 mg prolonged release formulation in Indian patients with type 2 diabetes mellitus: a postmarketing observational study</p>

PurposeThe aim of this study was to understand patient adherence, satisfaction, and experience with the smaller sized metformin 500 mg prolonged release (PR) tablet that has been manufactured with the help of technological advancement (Gluformin I 500 mg), in comparison with metformin 500 mg extended-release (ER) tablet, in patients with type 2 diabetes mellitus (T2DM).Patients and methodsIn this postmarketing observational study, T2DM patients who were on a stable dose of metformin 500 mg PR tablet for at least 1 month and had previously received metformin 500 mg ER tablet were recruited from 50 sites in India. The medication adherence and patients’ experience, satisfaction, and perception with metformin 500 mg PR tablets were compared with metformin 500 mg ER tablets. The patients’ experience was determined based on the external appearance of tablet, ease of swallowing, the presence of gastrointestinal discomfort, and ghost pill effect.ResultsA total of 1,000 patients were enrolled. The majority had medium adherence to metformin 500 mg PR tablet (54%) and did not report swallowing difficulties (66.2%) due to its small size (64.4%) and oval shape (64.3%). The PR formulation of metformin was more acceptable than ER formulation due to no aftertaste (63%). The ghost pill effect was reported in 0.7% of patients with metformin 500 mg PR tablet against 8.5% with ER tablet. More than 60% of patients were “comfortable” (67.9%), had “much effect on their well-being” (61.8%), and were “satisfied” (69%) with metformin 500 mg PR tablet compared with ER tablet. Patient’s dissatisfaction (42.7%) and taste (24.9%) were the common reasons cited by physicians and patients, respectively, for changing the treatment from metformin 500 mg ER to metformin 500 mg PR formulation. A total of 10 adverse events (nonserious) were reported, and all of them were resolved.ConclusionThe technologically advanced formulation of metformin 500 mg PR tablets is more effective than that of metformin 500 mg ER tablets in improving adherence, compliance, satisfaction, and perception to medication in Indian patients with T2DM.

Effectiveness of monthly intravenous ibandronate injections in a real-world setting: Subgroup analysis of a postmarketing observational study

ObjectivesThe favorable safety and consistent effectiveness of monthly intravenous (IV) ibandronate injections was demonstrated in a prospective, postmarketing, observational study in Japanese patients with osteoporosis. Here, we present subgroup analyses from the study. MethodsLumbar spine (L2–4) bone mineral density (BMD) gains were assessed in the following subgroups: aged <75 or ≥75 years, absence or presence of vertebral fractures, previous bisphosphonate (BP) treatment, and concomitant versus naïve osteoporosis drug treatment. The cumulative incidence of fractures and relative change in bone turnover markers were also examined. ResultsOf 1062 enrolled patients, 1025 received monthly IV ibandronate 1 mg and were assessed for 12 months. BMD gains with ibandronate were comparable, irrespective of older age or prevalent fractures. Overall, 515 patients (50.2%) had previously received osteoporosis treatment; of these, 166 (16.1%) received other BPs. Mean BMD changes were 3.69% (95% confidence interval [CI], 0.89%–6.50%) in patients previously treated with other BPs, and 4.26% (95% CI, 2.88%–5.64%) in patients who had not received prior osteoporosis treatment. Among the 510 patients (49.7%) concomitantly prescribed active vitamin D drugs, mean BMD changes were 5.74% (95% CI, 2.53%–8.95%) with eldecalcitol versus 3.54% (95% CI, 1.98%–5.10%) with ibandronate alone. The lowest fracture incidence was observed with the combination of ibandronate and eldecalcitol, but differences between the subgroups were not statistically significant. ConclusionsMonthly IV ibandronate demonstrated comparable BMD gains in the patient subgroups analyzed. Concomitant use of ibandronate with eldecalcitol showed a trend of higher BMD gains and lower fracture incidence than ibandronate alone.

Safety Of 300IR 5-Grass Tablet In Grass Pollen–Allergic Children With Or Without Controlled Asthma: Further Data From A Post-Marketing Observational Study

Safety Of 300IR 5-Grass Tablet In Grass Pollen–Allergic Children With Or Without Controlled Asthma: Further Data From A Post-Marketing Observational Study

Abstract WP524: Outcomes With Rivaroxaban in Patients With Nonvalvular Atrial Fibrillation and Worsening Renal Function

Introduction: Direct oral anticoagulants are widely used in patients with nonvalvular atrial fibrillation (AF) to reduce the risk of stroke and systemic embolism, however, there is not enough real-world data of their effectiveness and safety in patients with worsening renal function (WRF). Xarelto post-authorization safety and effectiveness study in Japanese patients with atrial fibrillation (XAPASS) is a prospective observational post-marketing surveillance study mandated by the Japanese authority. It aims to examine safety and effectiveness of rivaroxaban in everyday clinical practice. This analysis investigated one year outcomes among patients with WRF and stable renal function (SRF) in XAPASS. Methods: One year follow-up data of 9578 patients enrolled in XAPASS were analyzed to evaluate baseline characteristics and safety/effectiveness profile among patients with WRF and SRF. WRF was defined as a decrease of more than 20% from enrollment creatinine clearance measurement at any time point during the study. SRF was defined as the absence of WRF at any time. Results: We identified 1229 patients (12.8%) with WRF and 6280 patients (65.6%) with SRF among 9578 patients. WRF patients were significantly older, and had significantly higher mean CHA 2 DS 2 -VASc score and modified HAS-BLED score compared to SRF patients. Prevalence of hypertension, congestive heart failure, ischemic stroke/transient ischemic attack, and myocardial infarction was higher in WRF patients. There was no difference in rates of major bleeding (hazard ratio (HR) 1.20; 95% confidence interval (CI) 0.75-1.90; p=0.45) or the composite endpoint of stroke, systemic embolism or myocardial infarction (HR 1.06; 95% CI 0.65-1.71; p=0.82) between patients with WRF and SRF. WRF patients experienced a higher incidence of transfusion of 2 units or more (0.46 versus 0.14 events per 100 patient-years; HR 3.19; 95% CI 1.04-9.74; p=0.03) versus SRF patients. Rates of other major bleeding subgroups defined according to ISTH criteria were similar between patients with WRF and SRF. Conclusions: WRF during rivaroxaban treatment did not significantly increase the rates of major bleeding or thromboembolic events, although it was associated with a higher incidence of transfusion of 2 units or more.

Abstract WP528: Safety and Effectiveness of Rivaroxaban Among Japanese Elderly Patients With Nonvalvular Atrial Fibrillation in Everyday Clinical Practice

Introduction: Nonvalvular atrial fibrillation (AF) is common in elderly patients, who face increased risk of thromboembolism and bleeding during antithrombotic therapy. Xarelto post-authorization safety &amp; effectiveness study in Japanese patients with atrial fibrillation (XAPASS) is a prospective observational post-marketing surveillance study mandated by the Japanese authority. It aims to examine safety and effectiveness of rivaroxaban in everyday clinical practice. This analysis evaluated one-year outcomes and patient characteristics associated with major bleeding or thromboembolic events among elderly patients enrolled in XAPASS. Methods: A total of 11,308 patients with AF newly starting rivaroxaban were enrolled between April 2012 and June 2014. As of September 2017, one year follow-up data were collected from 9578 patients, and 4685 patients (48.9%) were aged ≥75 years. Results: Patients aged ≥75 years had higher rates of major bleeding (2.22 versus 1.35 events per 100 patient-years; p=0.004), and the composite endpoint of stroke, systemic embolism or myocardial infarction (2.41 versus 1.21 events per 100 patient-years; p&lt;0.0001) compared with those aged &lt;75 years. Rates of intracranial hemorrhage were less than 1% in both patient groups aged ≥75 years and &lt;75 years (0.85 versus 0.59 events per 100 patient-years). There was no significant difference in major bleeding or thromboembolism among patients in age groups of 75-79, 80-84, and ≥85 years. Multivariate analysis identified hepatic impairment and concomitant use of acetylsalicylic acid as risk factors of major bleeding events in patients aged ≥75 years (p=0.041 and p&lt;0.0001, respectively). History of stroke was identified as a risk factor of thromboembolic events in the same patient group (p&lt;0.0001). Conclusions: Although elderly patients had higher rates of bleeding and thromboembolic events than younger patients, no significant difference was found in the outcomes between age groups of 75-79, 80-84, and ≥85 years. Benefit and risk of antithrombotic therapy should be thoroughly assessed in elderly patients. Additionally, elderly patients with risk factors of bleeding or thromboembolic events should be carefully monitored while taking anticoagulants.

Post-Marketing Surveillance of Hepatitis A Virus Vaccine (Avaxim® 160U) in South Korea from 2011 to 2015

IntroductionHepatitis A, caused by hepatitis A virus (HAV), is one of the leading causes of acute hepatitis in South Korea. Avaxim® 160U is an inactivated hepatitis A vaccine that has been proven to be highly effective and well tolerated. It is licensed for use in more than 90 countries, and was approved for use in South Korea in 2011. Clinical trial and approval processes may not fully assess the safety and efficacy of a vaccine. Post-marketing surveillance (PMS) aims to provide a complete safety profile of a vaccine in a real-life setting. PMS trials are mandatory in South Korea to retain drug licensure.MethodsThis post-marketing observational study (NCT01838070) was conducted over 4 years at 16 centres in South Korea, and aimed to observe and record all types of adverse events (AE) occurring in an adult population after vaccination with Avaxim® 160U. This included solicited events, unsolicited non-serious events, unexpected events and serious events.ResultsCase report forms were collected from 614 vaccinees, all of whom completed 30 days of follow-up post-vaccination, of whom 36 (5.9%) experienced 53 solicited and unsolicited AEs, 17 (2.8%) experienced 22 of the solicited AEs, while there were no reports of AEs of severe intensity. A total of 31 unsolicited AEs were reported in 22 patients (3.6%), and no unexpected adverse drug reactions were reported.ConclusionNo new safety issues were identified and the safety profile obtained from this study was comparable to that of previous studies for HAV vaccine.Trial RegistrationClinicalTrials.gov identifier, NCT01838070.FundingSanofi Pasteur.

Omalizumab as a Provoking Factor for Venous Thromboembolism

A 43-year-old man with a history of severe extrinsic allergic asthma treated with once-monthly omalizumab (600 mg) for the last 15 months. He presented to the emergency room with a 2-week history of right lower limb pain and chest pleuritic pain. Computed tomography pulmonary angiography showed bilateral pulmonary embolism with right-sided pulmonary infarction and ultrasound of right lower limb confirmed distal deep vein thrombosis. No other known risk factors were identified. Treatment with omalizumab was stopped during hospitalization. The Naranjo Adverse Drug Reaction (ADR) Probability Scale classifies this as a probable ADR (score of 6). Omalizumab is a humanized monoclonal anti-IgE antibody indicated for the treatment of persistent moderate-to-severe asthma and certain chronic refractory urticaria. The EXCELS study (The Epidemiologic Study of Xolair (omalizumab): Evaluating Clinical Effectiveness and Long-term Safety in Patients with Moderate-to-Severe Asthma), a postmarketing observational cohort study to assess clinical safety profile of omalizumab, showed a significant increase in venous thromboembolism. In conclusion, omalizumab has been associated with arterial and venous thromboembolic events, although the evidence is not definitive.

Assessment of Safety and Effectiveness of Glaritus&amp;lt;sup&amp;gt;&amp;amp;reg;&amp;lt;/sup&amp;gt; (Wockhardt’s Insulin Glargine) in a Prospective, Multi-Centric Post Marketing Observational Study in Nepalese Having Type 2 Diabetes Mellitus

Background: Nepal is one of the fastest urbanizing countries in South Asia and is facing the consequences of urban lifestyle leading to obesity and metabolic syndrome. Type 2 diabetes mellitus (T2DM) is currently a high-burden disease in Nepal with a prevalence of 8.4%. Of these 8% - 18% patients are on insulin and 42% patients were reported to have uncontrolled diabetes in the past year. This suggests a need for better therapy options in terms of efficacy and safety. The current study was designed to investigate the effects of Insulin glargine-based therapy in Nepalese with T2DM who could not achieve adequate glycemic control with oral and non-glargine-insulin therapy. Methods: This is a prospective, multi-centric, single arm and post marketing observational study to assess the safety and effectiveness of Glaritus® (Wockhardt’s Insulin Glargine) in 52 T2DM patients from 3 (three) different study sites in Nepal (Bharatpur, Kathmandu and Pokhra) from September 2015 to December 2016. The primary objective of the study was to evaluate the safety of Glaritus®, mainly in terms of hypoglycemia, renal function tests and liver function tests. The secondary objectives were to evaluate the effectiveness of Glaritus® in terms of percentage of patients achieving HbA1c goal of less than 7%, mean changes in HbA1c & fasting plasma glucose (FPG) levels from baseline till the end of study. Results: 3.85% of subjects experienced hypoglycemia during first 3 months of therapy whereas 1.92% had similar experience in next 3 months of therapy. The mean HbA1c values reduced from 9.16% to 7.15% at the end of study. 21.05% of the enrolled subjects achieved the goal of HbA1c < 7% at the end of 3 months of therapy, whereas 52.5% achieved the target HbA1c at the end of 6 months of therapy. The mean FPG value of study population reduced from 239.94 mg/dl to 151.31 mg/dl at the end of study. There was no significant change in renal or liver functions during treatment. None of the subjects experienced any other adverse event (AE), thus indicating that Glaritus® was well tolerated by the study patients. Conclusion: In patients with type 2 diabetes mellitus inadequately controlled on oral hypoglycemic agents and/or insulin, initiation with Glaritus® significantly improved glycemic control with good tolerability and acceptability. This analysis in T2DM Nepalese patients shows that by significantly improving glycemic control while not increasing risk of hypoglycemia, Glaritus® provides safer basal insulin and may be suited to aggressive treatment regimens. From a societal perspective, it will help more patients reach the glycemic control target as recommended by the current treatment guidelines.

Long-Term Mortality and Bone Safety in Patients with End-Stage Renal Disease Receiving Lanthanum Carbonate

Background/Aims: This post-marketing observational study assessed the long-term safety of lanthanum carbonate (LaC) in US patients with end-stage renal disease (NCT00567723). Methods: Patients (≥18 years old) undergoing dialysis, who had Medicare as their primary healthcare payer, and records in the United States Renal Data System were followed-up for 5 years. Patients who had received LaC for at least 12 consecutive weeks formed the exposed cohort. During the same time period, patients who had undergone dialysis for at least 12 consecutive weeks and had been treated with any other phosphate binder formed the primary comparator cohort. A historical cohort was also evaluated. Primary outcomes were all-cause mortality, and time to and incidence of first bone-fracture event requiring hospitalization. Secondary outcomes were time to first occurrence of and incidence of specific gastrointestinal (GI) disease, liver disease, malignancy, and major infectious episode requiring hospitalization. ­Results: 2,026 and 8,094 patients were included in the exposed and primary comparator cohorts, respectively. A Cox proportional hazards model showed that patients receiving LaC were not at increased risk of all-cause mortality (adjusted hazard ratio 0.94; 95% CI 0.88–1.01; p = 0.078), bone fractures (0.86; 0.71–1.05; p = 0.130), specific GI disease (0.86; 0.76–0.97; p = 0.015), liver disease (0.88; 0.70–1.09; p = 0.236), malignancy (0.85; 0.54–1.34; p = 0.496), or major infectious episodes (0.87; 0.80–0.94; p < 0.001) requiring hospitalization compared with primary comparator patients. Conclusions: LaC was not associated with increased risk of mortality, bone fractures, or any secondary outcome.

Chemotherapy-induced peripheral neuropathy in breast cancer patients treated with eribulin: interim data from a post-marketing observational study

BackgroundFew studies have examined chemotherapy-induced peripheral neuropathy (CIPN) following the administration of eribulin as first- or second-line therapy in patients with breast cancer. We therefore assessed CIPN incidence by severity and risk factors for CIPN in patients treated with eribulin for HER2-negative inoperable or recurrent breast cancer, regardless of line therapy status.MethodsThis multicenter, prospective, post-marketing observational study enrolled patients from September 2014 in Japan and followed them for 2 years. For this interim analysis, the data cut-off point was in November 2017. CIPN severity was assessed based on the Japanese version of the Common Terminology Criteria for Adverse Events, version 4.0.ResultsAmong 634 patients included in the safety analysis, 374 patients did not have existing CIPN at baseline. CIPN was observed in 105 patients (28.1%), including 67 (17.9%), 34 (9.1%), and 4 (1.1%) patients with grade 1, 2, and 3 severity, respectively. Of the 105 patients, 85.7% patients continued, 7.6% reduced, interrupted or postponed, and 6.7% discontinued eribulin. The median time (min‒max) from baseline to CIPN onset was 60 (3‒337) days. Multivariate logistic regression identified a significant association between CIPN and hemoglobin level at baseline, starting dose of eribulin, and history of radiotherapy.ConclusionsOur findings indicate that, with respect to CIPN, eribulin is well-tolerated, as approximately one-quarter of patients developed CIPN, most cases were grade 1 or 2, and the majority of patients continued eribulin after CIPN onset.