Evaluation of Health-Related Quality of Life (HRQL) in ABSSSI Patients After Antibiotic Discontinuation in a Phase 3 Trial

RESULTS CONCLUSIONS Melinta Therapeutics 203-624-5606 info@melinta.com ID Week 2015 San Diego, CA, USA Oct. 7-11, 2015 Background: Limited heath-related quality of life (HRQL) data exist for patients with acute bacterial skin and skin structure infections (ABSSSIs). This analysis evaluates HRQL in patients with a positive clinical response (cured [complete resolution of all baseline signs and symptoms] or improved [some symptoms remain but no further antibiotics are necessary]) in patients enrolled in an ABSSSI Phase 3 trial. Methods: Adult patients diagnosed with ABSSSI were enrolled in a prospective Phase 3, randomized, double-blind study to evaluate antibiotic treatment. Investigators were asked to assess patients with a positive clinical response as cured or improved at the end of treatment (EOT), follow up (FU, study day 14±1) and late follow up (LFU, study day 21-28). An analysis was conducted to understand the difference between cured and improved patients with respect to patient-reported HRQL as measured by the Extremity Soft Tissue Infection (ESTI) score,1 a 20-question survey with a 5-point Likert scale (5=highest degree of importance/impairment to the patients); measured symptoms; daily functioning; emotional functioning; and social interactions. Results: 660 patients were enrolled in this study and 589 patients had data for inclusion in this analysis. Overall, improved patients had more difficulties with HRQL measures than cured patients. Approximately 20% of the improved patients at EOT did not proceed to cure by LFU. The ESTI score was statistically higher at LFU in improved patients than in cured patients. At LFU, improved patients were more likely than cured patients to report having continued difficulty performing a job and earning an income. Obese patients, who comprised 29% of the patients in the study, reported even greater difficulty with HRQL measures. Results are shown below. BMI ≥30 kg/m2 BMI <30 kg/m2 Cured (n=140) Improved (n=31) Pvalue Cured (n=312) Improved (n=49) Pvalue Overall ESTI score (mean) 26.3 46.4 .0289 25.5 35.7 .1305 Patients reporting difficulty (%) Doing a job 9.6 29.0 .0075 8.4 27.1 .0006 Earning an income 14.0 32.3 .0320 9.4 27.1 .0013 Conclusions: Patients who had residual signs/symptoms (improved) when the physician stopped antibiotics at EOT had more difficulty than cured patients with HRQL measures at LFU. Improved patients at EOT, particularly those who are obese, may have persistent HRQL issues that require further utilization of healthcare resources. Additional research is needed to determine the potential economic impact of these data. Acute bacterial skin and skin structure infections (ABSSSIs) may be responsible for a considerable amount of hospital readmissions. In a retrospective cohort study in a 900-bed teaching hospital, readmission/mortality rates (within 30 days) were 26% for healthcare-associated ABSSSIs and 12% for community-acquired ABSSSIs.2 Obesity is a significant risk factor for antibiotic treatment failure3 and high readmission rates. In a retrospective cohort study, 38.6% of patients who were obese and admitted for cellulitis were classified as “30-day bounce backs,” including readmissions (12.4%); visits to the ER (10.9%), outpatient clinic (11.4%), or urgent care center (2.9%); and self-care (1.0%).4 When treating ABSSSIs, a healthcare provider’s (HCP’s) decision to stop antibiotics is empirical. • Typically the HCP stops antibiotics when they feel that the patient is cured (ie, no remaining signs or symptoms) or significantly improved, in which some but not all signs and symptoms have resolved. In this case, the HCP assumes that all remaining signs and symptoms will resolve over time so that the patient is fully cured without further antibiotics. • Limited data exist on the outcome of patients who are cured versus improved after antibiotic discontinuation. An analysis was conducted to assess the difference between cured and improved patients (including obese and non-obese subgroups) with respect to lesion size; signs and symptoms; pain score; and patientreported HRQL to understand what patients “look like” when their antibiotics are discontinued (ie, what separates a cured from an improved patient), and to understand if the physician’s assumption of their patients’ progression from “improved” to “cured” over time is correct. STUDY DESIGN • Adult patients with a diagnosis of ABSSSI were enrolled in a prospective Phase 3, randomized, double-blind study to evaluate antibiotic treatment. • At baseline, patients were required to have a minimum ABSSSI lesion size of 75 cm2 and at least 2 systemic manifestations of infection. • Antibiotic therapy was required for a minimum of 5 days, extending up to 14 days at the discretion of the investigator. • Signs and symptoms were assessed at each visit. The 8 signs/symptoms included drainage/discharge; erythema/extension of redness; fluctuance; heat/localized warmth; swelling/induration; pain/tenderness; lymphangitis; and lymphadenopathy. • Lesion size was assessed at each visit by digital planimetry. • Patients assessed pain via a numerical rating scale (0=no pain, 10=worst pain; typically a change in pain score of approximately 1.3 is the minimally clinically important difference2). • The investigator was asked for their clinical assessment of the patient’s outcome as defined as • Cured: The complete resolution of all baseline signs and symptoms of ABSSSI • Improved: Some symptoms remained, but the patient was improved to an extent that no additional antibiotic treatment was necessary • Failure: Worsening of signs and symptoms that required unplanned surgical intervention, or nonstudy antibacterial drug therapy was required because of lack of efficacy • Indeterminate: A response could not be assigned because an assessment was not completed at the follow up (FU, study day 14±1) or late follow up (LFU, study day 21-28), or because the patient received potentially effective nonstudy antibacterial drug therapy for treatment of a condition other than ABSSSI unless that patient was categorized as a failure HEALTH-RELATED QUALITY OF LIFE (HRQL) MEASUREMENT An HRQL assessment was completed for all patients, as measured by a questionnaire utilizing the Extremity Soft Tissue Infections (ESTI) score. • The ESTI score is a novel instrument designed to quantify the impact of extremity soft tissue infections on the following quality of life parameters. • Symptoms: Pain, swelling, trouble moving, stiffness, soreness, pressure, and throbbing • Daily functioning: Doing your job, walking, bathing, changing clothes, earning an income, exercising, and falling asleep • Emotional functioning: Frustrated, disappointed, annoyed, exhausted, and inconvenienced • Social interactions: Inconveniencing family and friends • Patients were asked to respond yes/no to whether they were experiencing difficulty with each item and then rank the “importance” using a 5-point Likert scale. A higher ESTI score represents more difficulties with the HRQL measure. This full menu of assessments was performed at the end of treatment (EOT) and was repeated at FU and LFU. The analysis was conducted for all patients, as well as by body mass index (BMI) (non-obese, patient BMI <30 kg/m2; obese, patient BMI ≥30 kg/m2). METHODS