P59 Baseline characteristics and medical history of patients with refractory or unexplained chronic cough participating in two global phase 3 clinical trials

Abstract Background The risk of serious infections and poor treatment outcomes is reported to be higher in patients with diabetes compared with the general population. Omadacycline (OMC) is an intravenous (IV) and oral aminomethylcycline antibiotic approved in the US to treat acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP) in adults. Here we assessed safety and efficacy results from OMC Phase 3 studies (ABSSSI: Omadacycline in Acute Skin and skin structure Infections Study [OASIS]-1 and OASIS-2; CABP: Omadacycline for Pneumonia Treatment In the Community study [OPTIC]), by diabetes history. Methods In OASIS-1 (IV to optional oral medication) and OASIS-2 (oral only), patients were randomized to OMC or linezolid (LZD) for 7–14 days. In OPTIC, patients were randomized to IV OMC or moxifloxacin (MOX) for 7–14 days, with optional transition to oral medication. Data from OASIS-1 and OASIS-2 were pooled, and patient subgroups were defined by any medical history of diabetes (type 1, type 2, or unspecified), or no medical history of diabetes. Efficacy outcomes were early clinical response (ECR) and investigator’s assessment of clinical response at post-treatment evaluation (PTE), as defined for each indication. Safety was assessed by treatment-emergent adverse events (TEAEs) and laboratory measures, and data were pooled across the three studies. Results A total of 2,150 patients were included, of whom 238 (11.1%) had any history of diabetes (n = 105 for ABSSSI, n = 133 for CABP). In the pooled ABSSSI studies and the CABP study, clinical success at ECR and PTE was similar between patients with or without diabetes, and between OMC and the respective comparator (figure). TEAEs and serious TEAEs, respectively, were reported in similar numbers of OMC-, LZD-, and MOX-treated patients with diabetes (41.8–49.3%, 4.5–7.0%) and without (41.2–48.3%, 1.6–6.9%). Rates of nausea and vomiting, respectively, in patients with diabetes were similar across treatment arms: OMC (5.0%, 5.0%), LZD (7.5%, 6.0%), MOX (7.0%, 2.8%). Conclusion Omadacycline efficacy and safety were similar and consistent in patients with or without diabetes. Disclosures All authors: No reported disclosures.

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Osteoarticular Pain after Discontinuation of Tyrosine Kinase Inhibitors (TKI): A French Cohort

Blood ◽

10.1182/blood.v126.23.137.137 ◽

2015 ◽

Vol 126 (23) ◽

pp. 137-137 ◽

Cited By ~ 9

Author(s):

Marc G Berger ◽

Bruno Pereira ◽

Charlotte Oris ◽

Sandrine Saugues ◽

Pascale Cony-Makhoul ◽

...

Keyword(s):

Clinical Trials ◽

Tyrosine Kinase ◽

Medical History ◽

Board Of Directors ◽

Tyrosine Kinase Inhibitors ◽

Research Funding ◽

Kinase Inhibitors ◽

Duration Of Treatment ◽

Advisory Committees ◽

History Of

Abstract Context: The Tyrosine Kinase Inhibitors (TKIs) have revolutionized the treatment of chronic myeloid leukemia (CML) increasing dramatically the survival of CML patients and leading to a residual disease with a sustained and deep molecular response. In this subset of very good responder patients, the attempts of stopping treatment in different clinical trials were successfully achieved without relapse. The Swedish team in the EURO-SKI protocol already reported cases of musculoskeletal pain occurring after cessation of TKI (Richter et al., JCO, 2014). Since several clinical trials regarding TKI discontinuation have been also run in France, we decided to retrospectively collect data using the pharmacovigilance system of the different Trials collected prospectively. Method: 428 patients from STIM2 (n=204) and EURO-SKI (n=224) trials were systematically analyzed from the case report from each trial. For the EURO-SKI only French patients were included. Statistical analysis was performed using Stata 13 software (StataCorp LP, College Station, TX, US). Comparisons between the independent groups were realized using the Chi-squared or Fisher's exact tests for categorical variables, and using Student t-test or Mann-Whitney test for quantitative. Multivariate analyses were performed to take into account adjustment on covariates fixed according to univariate results and clinically relevance. Results: Among the 428 patients the main characteristics were as follow i,e; 208 (48.6%) men and 220 (51.4%) women, with a median age of 77.5 years (24-93). Sokal scores (n=449) were low in 187 (41.6%) patients, intermediate in 188 (41.9%) patients and high in 74 (16.5%) patients. A withdrawal TKI syndrome (WS) was reported for 102 (23.8%) patients (100 after imatinib and 2 after nilotinib). 2). The WS consists in bone and articular pains and arthritis and affects the upper limbs, shoulders and cervical rachis, with a grade 1 or 2 in most patients and grade 3 in 22% of patients . The prevalence of WS depends on the trials, 34.8% in EURO-SKI group and 13.8% in STIM2 group (p<0.001). The WS was treated by non-steroidal anti-inflammatory drugs, corticosteroids or by local infiltration. The median duration of WS was 7 months (range: 3-30 months, 24 exploitable cases). We did not observe any difference between WS group and the group without painful syndrome in terms of sex ratio (p=0.92), age (p=0.33), sokal score (p=0.15), BCR-ABL transcript (p=0.42) or duration of CML (p=0.24). However the median duration of TKI therapy appeared longer in this subgroup (median: 88.8 months vs 79.8 months (p=0.02). There was no biological inflammatory syndrome and the results of medical imaging were inconclusive. However, a medical history of osteoarticular pains or disease appeared as predisposing to withdrawal syndrome (22.9% in WS group vs 9.8% in control group; p=0.002). Finally the two factors, duration of treatment and medical history were confirmed using multivariate analysis (RR=1.73 and 1.76 respectively). Among 19 exploitable cases suffering CML relapse and requiring further TKI treatment, pain disappeared in 7 patients (37%) within a median period of 3.5 weeks. Conclusion: About 23% of patients who stopped TKIs experienced a TKI WS and all TKI seems to be concerned. The predisposing factors were a medical history of osteoarticular pain or disease, and the duration of treatment. So patients and physicians should be aware and recommendations should be proposed for patients who have treated longtime with a history of arthritis. Disclosures Legros: Novartis: Research Funding, Speakers Bureau; ARIAD: Speakers Bureau; BMS: Speakers Bureau. Nicolini:Ariad Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Rousselot:Novartis: Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; ARIAD: Consultancy, Speakers Bureau; BMS: Consultancy, Speakers Bureau. Rea:Novartis: Honoraria; BMS: Honoraria; Ariad: Honoraria; Pfizer: Honoraria. Mahon:Bristol-Myers Squibb: Consultancy, Honoraria; ARIAD: Consultancy; Novartis: Consultancy, Honoraria; Pfizer: Consultancy.

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