Bosny Pierre-Louis

Association between plasma concentrations of certolizumab pegol and endoscopic outcomes of patients with Crohn's disease

BACKGROUND & AIMS Monitoring plasma concentrations of anti-tumor necrosis factor agents could optimize treatment of patients with Crohns Disease (CD). In a post hoc analysis of data from a clinical trial, we compared the relationship between plasma concentrations of certolizumab pegol (CZP) and endoscopic and clinical responses and remission with CZP therapy in patients with moderate to severe ileocolonic CD. METHODS We analyzed data from the Endoscopic Mucosal Improvement in Patients with Active CD Treated with CZP trial, from 89 adult patients with active endoscopic CD (ulceration in ≥ 2 intestinal segments and CD Endoscopic Index of Severity [CDEIS] scores of ≥ 8 points). Patients received subcutaneous CZP (400 mg) at weeks 0, 2, and 4 and then every 4 weeks until week 52. Endoscopic evaluations were performed at weeks 0, 10, and 54. Blood samples were collected to measure CZP plasma concentrations at weeks 8 and 54. CZP quartiles at weeks 8 (n = 80) and 54 (n = 45) were correlated with endoscopic response (>5-point decrease in CDEIS from baseline) and remission (CDEIS, <6) at weeks 10 and 54, respectively. RESULTS Higher concentrations of CZP at week 8 were associated with endoscopic response (P = .0016) and remission (P = .0302) at week 10 (n = 45). At week 54, the rates of endoscopic remission correlated with plasma concentrations of CZP (P = .0206). There was a significant inverse relationship between plasma concentrations of CZP and baseline levels of C-reactive protein and body weight (P = .0014 and P = .0373, respectively). CONCLUSIONS Endoscopic response and remission are associated with higher plasma concentrations of CZP in patients with moderate to severe ileocolonic CD. These results support the need to consider the pharmacokinetics of anti-tumor necrosis factor agents and therapeutic drug monitoring to optimize treatment. Clinicaltrials.gov Number, NCT00297648.

Long‐term safety and efficacy of certolizumab pegol in the treatment of Crohn's disease: 7‐year results from the PRECiSE 3 study

The efficacy and safety of certolizumab pegol (CZP) in moderate‐to‐severe Crohns disease were demonstrated in two 26‐week double‐blind studies (PRECiSE 1 & 2).

Clinical and demographic characteristics predictive of treatment outcomes for certolizumab pegol in moderate to severe Crohn's disease: analyses from the 7-year PRECiSE 3 study

Clinical factors were previously identified as predictors of short‐term treatment efficacy in Crohns disease (CD). The PRECiSE 3 (P3) 7‐year trial provides an opportunity to study predictors of short‐ and long‐term clinical remission among CD patients treated with certolizumab pegol (CZP).

Lacosamide and concomitant use of antiepileptic and other medications in a US population — A retrospective cohort study ☆

Information on the use of lacosamide and concomitant antiepileptic and non-antiepileptic drugs (non-AEDs) is available from clinical trials and observational studies with small sample sizes. This retrospective cohort study was conducted to gain insight into the use of lacosamide in a large number of patients with epilepsy in real-life clinical practice with less restrictive selection criteria compared with clinical trial participants. The Truven Health MarketScan (Commercial Claims and Medicare Supplemental) database was used to identify patients with a prior diagnosis of epilepsy with at least one prescription claim for lacosamide between June 2009 and September 2013 and continuous health insurance enrolment with medical and pharmacy coverage during the 1-year pre-index baseline period. A total of 8859 eligible patients were identified, of whom, at index (lacosamide initiation), 16.8% received lacosamide as monotherapy and 54.0% as polytherapy. The median prescription duration was 196days (Interquartile range 69-476days). Levetiracetam was the most frequently prescribed concomitant AED across all age groups, followed by phenytoin among older (>65years) and lamotrigine among younger patients. Older patients who had LCM monotherapy at initiation, were prescribed fewer concomitant AEDs, but more non-AEDs. The most common non-AED medications were prescribed for pain, psychiatric conditions, hyperlipidemia and gastrointestinal diseases across all age groups. Overall, results suggest that the lacosamide use is driven predominantly by age and that there is substantial use of lacosamide monotherapy (16.8%), despite lack of indication at the time of the study. Results also reveal substantial use of concomitant non-AEDs; 90.4% among patients >65years of age and 54.3% among those ≤17years, confirming the high prevalence of comorbidities among patients with epilepsy across all ages. Despite the availability of numerous newer AEDs, older AEDs are still being frequently prescribed, especially for elderly patients, notably phenytoin. This warrants careful consideration, given the strong propensity of enzyme-inducing AEDs to interact with other drugs, producing unwanted side effects. These results highlight the value of real-life prescription patterns and the potential in informing treatment decisions to ensure patients receive appropriate treatment.

Efficacy of Certolizumab Pegol in Crohn's Disease: Response to Ford et al.

To the Editor: In a recent meta-analysis, Ford et al. ( 1 ) reported results of an analysis of pooled data from randomized, controlled trials of anti-tumor necrosis factor (TNF) biological therapies in infl ammatory bowel disease (IBD), to determine relative risk (RR) of failure to achieve remission in active disease and RR of relapse of acti vity in quiescent disease once remission had occurred with these agents. Th e authors indicated they used very conservative methodology in order to minimize over estimation of effi cacy of biological therapies. Th is approach concluded that, overall, anti-TNF agents are eff ective in inducing remission in moderate to severely active Crohn ’ s disease (CD), but that the most evidence of benefi t was obtained with infl iximab (IFX), adalimumab (ADA), and natalizumab compared with certolizumab pegol (CZP). Statistical analyses adjusted for the dosing schedule of the anti-TNF agents used indicated that in the case of CZP 400 mg, this agent was of borderline signifi cance vs. placebo (RR = 0.94; confi dence interval 0.89 – 1.00, P = 0.05). Th e authors of this letter would like to make two points in response to the fi ndings reported by Ford et al. First, the design and purpose of the CZP trials from which data were combined for these analyses were quite diff erent, raising a concern regarding the validity of combining disparate data. Specifi cally, the earlier phase 2 trials were single-dose ( 2 ) or multiple-dose ( 3 ) studies, and were neither CONFLICT OF INTEREST Th e authors are employees of UCB.

Characterizing Subpopulations with Better Response to Treatment Using Observational Data - an Epilepsy Case Study

Electronic health records and health insurance claims, providing observational data on millions of patients, offer great opportunities, and challenges, for population health studies. The objective of this study is identifying subpopulations that are likely to benefit from a given treatment using observational data. We refer to these subpopulations as “better responders” and focus on characterizing these using linear scores with a limited number of variables. Building upon well-established causal inference techniques for analyzing observational data, we propose two algorithms that generate such scores for identifying better responders, as well as methods for evaluating and comparing these scores. We applied our methodology to a large dataset of ~135,000 epilepsy patients derived from claims data. Out of this sample, 85,000 were used to characterize subpopulations with better response to next-generation (“Newer”) anti-epileptic drugs (AEDs), compared to an alternative treatment by first-generation (“Older”) AEDs. The remaining 50,000 epilepsy patients were then used to evaluate our scores. Our results demonstrate the ability of our scores to identify large subpopulations of epilepsy patients with significantly better response to newer AEDs.

The Relationship Between Plasma Concentrations of Certolizumab Pegol and Clinical Efficacy: Results From the PRECiSE 2 Trial: P-24

BACKGROUND: We retrospectively evaluated the relationship of certolizumab pegol plasma concentrations following induction therapy and clinical efficacy using data from the PRECiSE 2 trial. METHODS: Patients aged 18 years with moderate to severe Crohn’s disease who enrolled in PRECiSE 2 were given open-label (OL) induction of subcutaneous certolizumab pegol 400 mg at Weeks 0, 2, and 4. Clinical remission, defined as a Crohn’s disease Activity Index (CDAI) score of 150 points, was evaluated at Week 6. Plasma certolizumab pegol concentration was measured at Week 6 (2 weeks after the last induction dose) and was assessed by quartile. This post hoc analysis evaluated potential associations between certolizumab pegol plasma concentration and remission rates at 6 weeks. A multivariable linear regression analysis was performed to determine if certolizumab pegol plasma concentration at Week 6 is influenced by baseline factors, including C-reactive protein (CRP), body weight, immunosuppressant use, CDAI, and sex. RESULTS: 572 patients had certolizumab pegol plasma concentrations available at Week 6 (n 1⁄4 143 per quartile) following OL certolizumab pegol induction. Patients with certolizumab pegol plasma concentration in quartiles 1 and 2 had clinical remission rates of 41% and 44%, respectively, while those with a certolizumab pegol concentration in quartiles 3 and 4 had clinical remission rates of 57% and 55%, respectively (Table 1). A significant statistical correlation between plasma quartile and clinical remission was observed (P 1⁄4 0.0036). CRP level and body weight were inversely associated with certolizumab pegol quartile. A multivariable analysis showed that baseline CRP level and body weight were significant predictors of plasma certolizumab pegol concentration at Week 6 (Table 2). CONCLUSION(S): Baseline CRP level and body weight are significantly correlated with certolizumab pegol plasma concentration. Certolizumab pegol plasma concentration in the top 2 quartiles may predict a greater likelihood of achieving clinical remission following standard induction therapy. Further research to better understand these relationships for induction therapy as well as maintenance therapy with certolizumab pegol is warranted.