-
1.
Daratumumab Plus Bortezomib, Melphalan, and Prednisone Versus Standard of Care in Latin America for Transplant-Ineligible Newly Diagnosed Multiple Myeloma: Propensity Score Matching Analysis.
Hungria, V, Martínez-Baños, DM, Mateos, MV, Dimopoulos, MA, Cavo, M, Heeg, B, Garcia, A, Lam, A, Machnicki, G, He, J, et al
Advances in therapy. 2020;(12):4996-5009
-
-
Free full text
-
Abstract
INTRODUCTION The phase 3 ALCYONE study demonstrated significantly longer progression-free and overall survival (PFS/OS) and higher overall response rates (ORR) with daratumumab plus bortezomib, melphalan, and prednisone (D-VMP) versus VMP alone in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM). In Latin America, bortezomib- or thalidomide-based regimens remain standard of care (SoC) for this population. No head-to-head trials have compared D-VMP with SoC regimens used in Latin America. METHODS Propensity score matching (PSM) was used to control for baseline differences between patient populations and compare outcomes for D-VMP versus SoC regimens used in Latin America. Data for the D-VMP cohort were from the D-VMP arm of the ALCYONE trial (n = 350). Data for the SoC cohort were from the retrospective, observational Hemato-Oncology Latin America (HOLA) study, which included patients with NDMM who did not receive a transplant (n = 729). Propensity scores were estimated using logistic regression. Exact, optimal, and nearest-neighbor PSM were applied to pick the best-performing method. Doubly robust estimation was the base case, since some baseline imbalances persisted. RESULTS All 350 patients from the D-VMP arm of ALCYONE were included in OS/PFS analyses and 338 in ORR analysis; 478 and 324 patients, respectively, from HOLA were included in these analyses. Naïve comparison revealed important differences in baseline characteristics (age, chronic kidney disease, hypercalcemia, and International Staging System [ISS] stage). After nearest-neighbor matching, baseline characteristics, except ISS stage, were well balanced; comparisons favored D-VMP over SoC for OS (hazard ratio = 0.41; 95% confidence interval [CI] 0.25-0.66; P = 0.002) and PFS (hazard ratio = 0.48; 95% CI 0.35-0.67; P < 0.001). After exact matching, imbalances remained in age and ISS stage; comparisons favored D-VMP over SoC for ORR (odds ratio = 5.44; 95% CI 2.65-11.82; P < 0.001). CONCLUSION In transplant-ineligible patients with NDMM, D-VMP showed superior effectiveness versus bortezomib- and thalidomide-based regimens, supporting adoption of daratumumab-containing regimens in Latin America.
-
2.
Number of Patients Eligible for PCSK9 Inhibitors Based on Real-world Data From 2.5 Million Patients.
Zamora, A, Masana, L, Comas-Cufi, M, Plana, N, Vila, À, García-Gil, M, Alves-Cabratosa, L, Elosua, R, Marrugat, J, Ramos, R
Revista espanola de cardiologia (English ed.). 2018;(12):1010-1017
Abstract
INTRODUCTION AND OBJECTIVES PCSK9 inhibitors (PCSK9i) are safe and effective lipid-lowering drugs. Their main limitation is their high cost. The aim of this study was to estimate the number of patients eligible for treatment with PCSK9i according to distinct published criteria. METHODS Data were obtained from the Information System for the Development of Research in Primary Care. Included patients were equal to or older than 18 years and had at least 1 low-density lipoprotein cholesterol measurement recorded between 2006 and 2014 (n = 2 500 907). An indication for treatment with PCSK9i was assigned according to the following guidelines: National Health System, Spanish Society of Arteriosclerosis, Spanish Society of Cardiology, National Institute for Health and Care Excellence, and the European Society of Cardiology/European Atherosclerosis Society Task Force. Lipid-lowering treatment was defined as optimized if it reduced low-density lipoprotein levels by ≥ 50% and adherence was > 80%. RESULTS Among the Spanish population aged 18 years or older, the number of possible candidates to receive PCSK9i in an optimal lipid-lowering treatment scenario ranged from 0.1% to 1.7%, depending on the guideline considered. The subgroup of patients with the highest proportion of potential candidates consisted of patients with familial hypercholesterolemia, and the subgroup with the highest absolute number consisted of patients in secondary cardiovascular prevention. CONCLUSIONS The number of candidates to receive PCSK9i in conditions of real-world clinical practice is high and varies widely depending on the recommendations of distinct scientific societies.
-
3.
Effectiveness and safety of infliximab biosimilar CT-P13 in treating ulcerative colitis: a real‑life experience in IBD primary centers.
Tursi, A, Allegretta, L, Chiri, S, Della Valle, N, Elisei, W, Forti, G, Lorenzetti, R, Mocci, G, Penna, A, Pranzo, G, et al
Minerva gastroenterologica e dietologica. 2017;(4):313-318
Abstract
BACKGROUND The aim of this study was to assess the efficacy and safety of infliximab biosimilar (IFX) IFX CT-P13 in inducing and maintaining remission in ulcerative colitis (UC) outpatients in Italian primary gastroenterology centers. METHODS Patients were prospectively assessed at entry, after 8, 12, 24, 36, and therefore 52 weeks. Clinical activity was rated as per the Mayo Score. The primary endpoint was reaching of clinical remission (Mayo Score ≤2). Several secondary endpoints were clinical response to treatment, reaching of mucosal healing (MH), safety of the drug. RESULTS Twenty-nine patients (16 males and 13 females, mean age 45 years, range 35-42 years) were enrolled. Eleven (37.9%) patients had previous exposure to other anti-TNF-α. Clinical remission was present in 78.5% at week 24, and in 100% at 12-month follow-up. Subgroup analysis did not reveal significant differences in clinical remission between IFX-naïve patients and patients switching from originator to IFX biosimilar. A clinical response was observed in 92.3% at week 8, in 50.0% at week 16, in 100% at week 36 and in 100% at 12-month follow-up. MH occurred in 85.7% at week 24, and in 100% at 12-month follow-up Reduction of steroids was achieved in 92.3% at week 8, and in 100% during follow-up. One patient underwent proctocolectomy 3 weeks after starting IFX CT-P13. The median C-reactive protein and calprotectin levels during follow-up were significantly reduced during follow-up. No adverse events were observed during follow-up. CONCLUSIONS IFX CT-P13 seems to be very effective and safe in real-life experience at primary IBD centers.
-
4.
The PROSIT-BIO Cohort: A Prospective Observational Study of Patients with Inflammatory Bowel Disease Treated with Infliximab Biosimilar.
Fiorino, G, Manetti, N, Armuzzi, A, Orlando, A, Variola, A, Bonovas, S, Bossa, F, Maconi, G, DʼIncà, R, Lionetti, P, et al
Inflammatory bowel diseases. 2017;(2):233-243
Abstract
BACKGROUND Few data are available on the safety and efficacy of infliximab biosimilar CT-P13 in patients with ulcerative colitis and Crohn's disease. METHODS A prospective, multicenter, cohort study using a structured database. RESULTS Consecutive patients (313 Crohn's disease and 234 ulcerative colitis) were enrolled from 31 referral centers; 311 patients were naive to anti-tumor necrosis factor alpha, 139 had a previous exposure to biologics, and the remaining 97 were switched to CT-P13 after a mean of 18 ± 14 infusions of infliximab. The mean follow-up was 4.3 ± 2.8 months, and the total follow-up time was 195 patient-years. After 2061 infusions, 66 serious adverse events were reported (12.1%), 38 (6.9%) of them were infusion-related reactions. The biosimilar had to be stopped in 29 (5.3%) cases for severe infusion reactions (8 naive, 19 previous exposed, and 2 switch), and in further 16 patients (2.9%) for other serious adverse events. Infusion reactions were significantly more frequent in patients pre-exposed to infliximab than to other anti-tumor necrosis factor alpha (incidence rate ratio = 2.82, 95% CI: 1.05-7.9). The efficacy of the biosimilar was evaluated in 434 patients who received treatment for at least 8 weeks, using time-to-event methods for censored observations: 35 patients were primary failures (8.1%). After further 8, 16, and 24 weeks, the efficacy estimations were 95.7%, 86.4%, and 73.7% for naive, 97.2%, 85.2%, and 62.2% for pre-exposed, and 94.5%, 90.8%, and 78.9% for switch, respectively (log-rank P = 0.64). CONCLUSIONS Although no direct comparison was performed, preliminary data on efficacy and safety of CT-P13 were in line with those of infliximab.
-
5.
Induction Therapy With Biosimilar Infliximab in Children With Crohn Disease.
Sieczkowska-Golub, J, Meglicka, M, Plocek, A, Banaszkiewicz, A, Jarzębicka, D, Toporowska-Kowalska, E, Gawronska, A, Oracz, G, Kierkus, J
Journal of pediatric gastroenterology and nutrition. 2017;(3):285-288
Abstract
INTRODUCTION In most European countries, an infliximab biosimilar (CT-P13) is currently in common use. In vitro and in vivo studies have proved a high similarity between CT-P13 and the reference infliximab. CT-P13 was licensed for use in patients with Crohn disease (CD) based on the extrapolation of data from preclinical studies and clinical trials in rheumatology indications. The aim of this study was to assess the similarity between CT-P13 and the originator infliximab in induction therapy in CD paediatric patients. METHODS Thirty-six CD paediatric patients from 3 Polish academic centres who started biological therapy with CT-P13 were enrolled in this prospective, observational study. Patients received 3 induction doses (5 mg/kg) of CT-P13 at weeks 0, 2, 6. Assessment was performed before the first infusion and at week 14. RESULTS Overall 34/36 (94.4%) patients completed induction therapy with CT-P13. A clinical response or remission after 3 initial doses was achieved in 31/36 (86%) and 24/36 (67%) of patients, respectively. Clinically and statistically significant decreases in Paediatric Crohn's Disease Activity Index, C-reactive protein, and erythrocyte sedimentation rate were observed in the responders group. An allergic reaction during infusion, which led to treatment discontinuation, was observed in one case. CONCLUSIONS Induction therapy with CT-P13 in children with CD is effective. The profile appears similar to that reported for the reference infliximab. No unexpected adverse events occurred.
-
6.
Transition from LDL apheresis to evolocumab in heterozygous FH is equally effective in lowering LDL, without lowering HDL cholesterol.
Lappegård, KT, Enebakk, T, Thunhaug, H, Hovland, A
Atherosclerosis. 2016;:119-123
Abstract
BACKGROUND AND AIMS LDL apheresis is effective in reducing low-density lipoprotein (LDL) cholesterol (LDL-C) and clinical endpoints, however, the treatment is invasive and time consuming. In the present study, we explored lipid profiles and quality of life in patients with heterozygous familial hypercholesterolemia (FH) when altering the treatment regimen from weekly LDL apheresis to bi-weekly evolocumab treatment. METHODS Three patients with FH and coronary artery disease, established in LDL apheresis for 135 ± 13(SD) months, participated. The patients were examined with blood sampling before and after LDL apheresis (week 0), and before evolocumab administration (week 1-7), quality of life was assessed (week 1, 3, 7). RESULTS The historically highest, untreated LDL-C was 10.3 ± 0.8 mmol/L, during weekly LDL apheresis, 5.5 ± 0.9 mmol/L pre-apheresis and 1.2 ± 0.2 mmol/L post-apheresis (p = 0.02). One week after apheresis, LDL-C was 6.1 ± 0.7 mmol/L, after three (bi-weekly) injections of evolocumab, LDL-C was 5.0 ± 0.7 (p < 0.001). High-density lipoprotein cholesterol (HDL-C) was reduced from 1.0 ± 0.2 mmol/L pre- to 0.5 ± 0.1 mmol/L post-apheresis (p = 0.03), it increased after apheresis and remained constant during evolocumab treatment. Lipoprotein(a) (Lp(a)) decreased from 484 ± 76 mg/L pre- to 142 ± 15 mg/L post-apheresis (p = 0.02), but increased during evolocumab treatment, with a small increase from week one to week seven (p < 0.01). There was a non-significant trend towards an increase in perceived health status (week 0; 57 ± 21, week three; 65 ± 9 and week seven; 77 ± 10). CONCLUSIONS In the current study, we demonstrate reductions in LDL-C, HDL-C, triglycerides and Lp(a) during apheresis. Switching from LDL apheresis to evolocumab maintained the LDL-lowering effect but did not decrease HDL levels.
-
7.
Adalimumab therapy in children with Crohn disease previously treated with infliximab.
Cozijnsen, M, Duif, V, Kokke, F, Kindermann, A, van Rheenen, P, de Meij, T, Schaart, M, Damen, G, Norbruis, O, Pelleboer, R, et al
Journal of pediatric gastroenterology and nutrition. 2015;(2):205-10
Abstract
OBJECTIVES Adalimumab, a humanised anti-tumour necrosis factor antibody, is an effective treatment in adult patients with refractory Crohn disease (CD). The available literature on its efficacy in children remains limited. We aimed to evaluate the real-world efficacy in paediatric patients with CD and compare the efficacy between infliximab (IFX) nonresponders and patients who lost response to IFX. METHODS All Dutch patients with CD receiving adalimumab before the age of 18 years after previous IFX therapy were identified. We analysed longitudinal disease activity, assessed by the mathematically weighted Pediatric Crohn's Disease Activity Index (wPCDAI) or the physician global assessment (PGA), and adverse events (AEs). RESULTS Fifty-three patients with CD were included. Twelve patients received monotherapy and the others received combination treatment with thiopurines (n = 21), methotrexate (n = 11), steroids (n = 7), or exclusive enteral nutrition (n = 2). Median follow-up was 12 months (interquartile range 5-23). Remission was reached in 34 patients (64%, wPCDAI < 12.5 or PGA = 0) after a median of 3.3 months, and maintained by 50% for 2 years. Eleven patients (21%) reached response but not remission (decrease in wPCDAI ≥ 17.5 or decrease in PGA). Eighteen patients (34%) failed adalimumab treatment because of nonresponse (n = 4), lost response (n = 11), or AEs (n = 3). More IFX nonresponders failed adalimumab treatment than patients who lost response to IFX (2/3 vs 8/34, hazard ratio 18.8, 95% confidence interval 1.1-303.6). Only 1 patient encountered a serious AE, a severe but nonfatal infection. CONCLUSIONS In clinical practice, adalimumab induces remission in two-thirds of children with IFX refractory CD.
-
8.
Observational Retrospective Study of Altered Biodistribution of Tositumomab and 131I-Tositumomab.
Wahl, RL, Horner, TJ, Lin, TS, Kaminski, MS
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2015;(11):1800-3
Abstract
UNLABELLED The tositumomab/(131)I-tositumomab radioimmunotherapy regimen is administered as a dosimetric dose followed by a therapeutic dose. The biodistribution of the dosimetric dose is assessed by quantitative calculations of whole-body residence time (TBRT) and visual examination of whole-body γ-camera images, to determine the administered radioactivity dose and whether a therapeutic dose can be administered. We investigated whether altered biodistribution of (131)I-tositumomab could be identified using quantitative TBRT. METHODS BioClinica, Inc., provided γ-camera images to an independent reviewer to assess altered (131)I-tositumomab biodistribution in patients reported to a registry. RESULTS Of 2,649 therapeutic doses, 5 (0.2%) were cancelled because of altered biodistribution as determined by γ-camera images and TBRT. Of these, 3 γ-camera images were assessed by the independent reviewer; one showed altered biodistribution (0.04%) and was in agreement with the TBRT on-site calculation. CONCLUSION TBRT alone should be used to determine altered biodistribution and hence whether to administer the therapeutic dose.
-
9.
Infliximab restores the dysfunctional matrix remodeling protein and growth factor gene expression in patients with inflammatory bowel disease.
de Bruyn, M, Machiels, K, Vandooren, J, Lemmens, B, Van Lommel, L, Breynaert, C, Van der Goten, J, Staelens, D, Billiet, T, De Hertogh, G, et al
Inflammatory bowel diseases. 2014;(2):339-52
Abstract
BACKGROUND Matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), a disintegrin and metalloprotease with thrombospondin motifs [ADAM(TS)s] and growth factors are involved in inflammation and tissue damage and repair, all occurring in inflammatory bowel disease (IBD). We studied the impact of anti-inflammatory therapy with infliximab on mucosal expression of these tissue remodeling genes in patients with IBD. METHODS Mucosal gene expression of 23 MMPs, 4 TIMPs, 50 ADAM(TS)s, and 158 growth factors was investigated in 61 patients with IBD before and after the first infliximab therapy and in 12 controls, with microarrays and quantitative RT-PCR. Protein localization, mucosal gelatinase levels, and net gelatinolytic activity were investigated by immunohistochemistry, zymography analysis, and gelatin degradation assay, respectively. RESULTS In patients with active IBD before infliximab versus controls, gene expression of many MMPs, TIMPs, ADAM(TS)s, and growth factors was upregulated, whereas colonic expression of MMP28 and TGFA and ileal expression of ADAMDEC1 and AGT were downregulated. After controlling inflammation with infliximab, most gene dysregulations observed at baseline were restored in responders. Increased ratio of MMP1/TIMP1 expression at baseline in active IBD was restored in responders with colonic mucosal healing. With immunohistochemistry, protein localization differences of MMP1, MMP3, REG1A, and TIMP1 were shown between active IBD and control mucosa. With zymography analysis and gelatin degradation assay, higher gelatinase levels and net gelatinolytic activity were measured before infliximab and levels normalized after infliximab. CONCLUSIONS Our data suggest that suppression of inflammation results in the arrest of epithelial damage and subsequent mucosal healing. Therefore, the therapeutic potential of agents targeting MMPs or growth factors as primary therapy seems rather complex.