scholarly journals P718 Combination therapy of adalimumab with an immunomodulator is not more effective than adalimumab monotherapy in children with Crohn’s disease

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S578-S579
Author(s):  
M Matar ◽  
R Shamir ◽  
D Turner ◽  
E Broide ◽  
B Weiss ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Combination Therapy ◽  
Clinical Remission ◽  
Controlled Trial ◽  
Combination Group ◽  
Therapeutic Drug ◽  
Monotherapy Group ◽  
Serious Adverse Events ◽  
Significant Difference

Abstract Background The PAILOT trial was a randomised controlled trial aimed to evaluate proactive vs. reactive therapeutic drug monitoring in children with Crohn’s disease (CD) treated with adalimumab. Our aim, in this post-hoc analysis of the PAILOT trial, was to assess the efficacy and safety of adalimumab combination treatment in comparison to monotherapy at week 72 after adalimumab induction. Methods Participants were children 6–17 years old, biologic naïve, with moderate-to-severe CD, who responded to adalimumab induction at week 4. Patients receiving immunomodulators at baseline, maintained a stable dose until week 24; patients could then discontinue immunomodulators. At each visit patients were assessed for disease index, serum biomarkers, faecal calprotectin, adalimumab trough concentration and anti-adalimumab antibodies. Results Out of the 78 patients (29% female; mean age, 14.3 ± 2.6 years), 34 patients (44%) received combination therapy. During the study period there was no significant difference in the rates of sustained corticosteroid free clinical remission (25/34, 73% vs. 28/44, 63%; p = 0.35), and sustained composite outcome of clinical remission, CRP≤0.5 mg/dl and calprotectin≤150 µgr/gr (10/34, 29% vs. 14/44, 32%; p = 0.77) between the combination group and the monotherapy group, respectively. Clinical and biological outcomes did not differ between the proactive and reactive sub-groups within the combination and monotherapy groups. Adalimumab trough concentrations and immunogenicity were not significantly different between groups. The rate of serious adverse events was not significantly different between groups but numerically higher in the monotherapy group. Conclusion Combination therapy of adalimumab and an immunomodulator was not more effective than adalimumab monotherapy in children with CD.

scholarly journals Combination Therapy of Adalimumab With an Immunomodulator Is Not More Effective Than Adalimumab Monotherapy in Children With Crohn’s Disease: A Post Hoc Analysis of the PAILOT Randomized Controlled Trial

2019 ◽  
Vol 26 (11) ◽  
pp. 1627-1635 ◽  
Author(s):  
Manar Matar ◽  
Raanan Shamir ◽  
Dan Turner ◽  
Efrat Broide ◽  
Batia Weiss ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Combination Therapy ◽  
Clinical Remission ◽  
Controlled Trial ◽  
Monotherapy Group ◽  
Post Hoc Analysis ◽  
Randomized Controlled ◽  
Post Hoc

Abstract Background The PAILOT trial was a randomized controlled trial aimed to evaluate proactive vs reactive therapeutic drug monitoring in children with Crohn’s disease (CD) treated with adalimumab. Our aim in this post hoc analysis of the PAILOT trial was to assess the efficacy and safety of adalimumab combination treatment in comparison with monotherapy at week 72 after adalimumab induction. Methods Participants were children 6–17 years old, biologic naïve, with moderate to severe CD, who responded to adalimumab induction at week 4. Patients receiving immunomodulators at baseline maintained a stable dose until week 24; patients could then discontinue immunomodulators. At each visit, patients were assessed for disease index, serum biomarkers, fecal calprotectin, adalimumab trough concentration, and anti-adalimumab antibodies. Results Out of the 78 patients (29% female; mean age, 14.3 ± 2.6 years), 34 patients (44%) received combination therapy. During the study period, there was no significant difference in the rates of sustained corticosteroid-free clinical remission (25/34, 73%, vs 28/44, 63%; P = 0.35) or sustained composite outcome of clinical remission, C-reactive protein ≤0.5 mg/dL, and calprotectin ≤150 µg/g (10/34, 29%, vs 14/44, 32%; P = 0.77) between the combination group and the monotherapy group, respectively. Clinical and biological outcomes did not differ between the proactive and reactive subgroups within the combination and monotherapy groups. Adalimumab trough concentrations and immunogenicity were not significantly different between groups. The rate of serious adverse events was not significantly different between groups but was numerically higher in the monotherapy group. Conclusions Combination therapy of adalimumab and an immunomodulator was not more effective than adalimumab monotherapy in children with CD (ClinicalTrials.gov No. NCT02256462).

scholarly journals P587 Adalimumab in pediatric Crohn’s disease: A long-term multi-centre real-world experience

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S491-S492
Author(s):  
S Lawrence ◽  
H Huynh ◽  
W El-Matary ◽  
J DeBruyn ◽  
M Carroll ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Combination Therapy ◽  
Clinical Remission ◽  
Long Term Outcomes ◽  
Faecal Calprotectin ◽  
Significant Difference ◽  
Necrosis Factor

Abstract Background There is a paucity of data regarding long-term outcomes for adalimumab (ADA) in pediatric Crohn’s disease (CD). We describe the long-term effectiveness of ADA, in achieving clinical and biochemical remission in a Canadian multi-centre pediatric CD cohort. Moreover, we report the effects of prior anti-TNF exposure and use of a concomitant immunomodulator (IM) on durability of clinical and biochemical response. The primary outcome was 24-month corticosteroid (CS) free remission. Secondary objectives included biochemical and faecal calprotectin response over the study period. Methods Retrospective review of electronic records of all children aged 3–18 years with CD requiring ADA at 4 centres across Canada (Vancouver, Edmonton, Winnipeg and Calgary) between January 2005 and December 2017. Results One hundred and nine children (68% male; median age 13.07 [IQR 10.6–15.1]) with CD (L1 21.7%, L2 28.3%, L3 50%) were included with a median follow-up of 15.9 months [IQR 7.6–24]. Seventy-four patients (67.9%) were anti-tumour necrosis factor (TNF) naïve. Concomitant IM therapy was used in 51 (46.8%). CS free clinical remission at 24 months was observed in 45/66 (68%). Over time, the median PCDAI, CRP, ESR and faecal calprotectin significantly improved (Table 1). During follow-up, 36 (33%) patients discontinued ADA; 6 (5.5%) had primary non-response, 28 (25.7%) had secondary LOR and 2 (1.8%) had intolerance. At 24 months, clinical remission was achieved more frequently in patients who were Anti-TNF naïve (81% vs. 43.5% p 0.002). There was no significant difference in biochemical or faecal calprotectin outcomes between those who were bio-naive or experienced. There was no significant difference in the time to loss of response between those on monotherapy and combination therapy with an IM and ADA (HR 0.64 [95% CI 0.33–1.26] p0.2). Conclusion This study demonstrates that ADA is effective and durable in pediatric CD. Over 24 months, clinical, biochemical and faecal calprotectin improvement was seen. In our cohort, clinical response to ADA was greater in anti-TNF naïve compared with anti-TNF experienced patients; however,, biochemical and faecal calprotectin outcomes did not differ. ADA response appears durable with no significant difference in patients on monotherapy or combination therapy.

Concerns and Side Effects of Azathioprine During Adalimumab Induction and Maintenance Therapy for Japanese Patients With Crohn’s Disease: A Subanalysis of a Prospective Randomised Clinical Trial [DIAMOND Study]

2019 ◽  
Vol 13 (9) ◽  
pp. 1097-1104 ◽  
Author(s):  
Tadakazu Hisamatsu ◽  
Takayuki Matsumoto ◽  
Kenji Watanabe ◽  
Hiroshi Nakase ◽  
Satoshi Motoya ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Side Effects ◽  
Crohn's Disease ◽  
Adverse Effects ◽  
Multivariable Analysis ◽  
Dropout Rate ◽  
Rank Test ◽  
Combination Group ◽  
Monotherapy Group ◽  
Significant Difference

Abstract Background Combining a thiopurine with the human anti-tumour necrosis factor-α monoclonal antibody adalimumab for Crohn’s disease [CD] treatment is controversial with regard to efficacy and safety. By conducting a subanalysis of a multicentre, randomised, prospective, open-label trial [the DIAMOND study, UMIN registration number 000005146], we studied the risk of discontinuation of thiopurine in combination with adalimumab. Methods In the preceding DIAMOND study, we analysed the: [i] timing and reasons for dropout in the monotherapy group and combination group; [ii] risk factors for dropout in the combination group. Results There was no significant difference in the dropout rate up to Week 52 between the monotherapy group and combination group [p = 0.325]. The main reason for study dropout was active CD in the monotherapy group, whereas it was adverse effects in the combination group [Fisher’s exact test, p <0.001]. Kaplan–Meier analyses revealed significantly earlier dropout in the combination group [log-rank test, p = 0.001]. Multivariable analysis revealed low body weight to be a risk for dropout due to adverse effects in the combination group. Conclusions Combination of azathioprine with adalimumab resulted in dropout in the early stage of the study due to side effects of azathioprine, in comparison with late dropout due to active CD in the adalimumab monotherapy group.

P084 DEEP REMISSION WITH DOUBLE BIOLOGIC THERAPY: A SUCCESSFUL CASE OF COMBINATION USTEKINUMAB AND VEDOLIZUMAB FOR SEVERE REFRACTORY CROHN’S DISEASE

2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S72-S72
Author(s):  
Ahmed Elmoursi ◽  
Courtney Perry ◽  
Terrence Barrett
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Combination Therapy ◽  
Clinical Remission ◽  
Biologic Therapy ◽  
Case Reports ◽  
Sigmoid Resection ◽  
Safety And Efficacy ◽  
Ileal Stricture

Abstract Background Stricturing Crohn’s disease (CD) constitutes a severe phenotype often associated with a high degree of morbidity (3). Surgical resection is first-line therapy for symptomatic strictures, but most patients relapse without subsequent medical therapy (4–5). Biologics are the mainstay for inducing and maintaining remission, but some cases are refractory despite maximum dosage of therapy. Reports of dual biological therapy (DBT) in refractory, stricturing CD are sparse, and prior case reports document only clinical remission (1). To contribute further knowledge regarding the use of DBT in stricturing CD, we present the case of a refractory CD patient who achieved deep remission with ustekinumab and vedolizumab. Case Presentation A 35 year old non-smoking, Caucasian male was referred to our clinic in 2014 for refractory CD complicated by multiple strictures. Prior to establishing care with us, he received two jejunal resections and a sigmoid resection. Previously failed therapies included azathioprine with infliximab, adalimumab, and certolizumab. He continued to progress under our care despite combination methotrexate/certolizumab, as well as methotrexate/golimumab. He underwent proctocolectomy with end ileostomy in 2015 and initiated vedolizumab q8weeks post-operatively. He reoccurred in 2018, when he presented with an ulcerated ileal stricture. He was switched from vedolizumab to ustekinumab q8weeks and placed on prednisone, but continued to progress, developing significant hematochezia requiring hospitalization and blood transfusions. Ileoscopy performed during hospital admission confirmed severe, ulcerating disease in the ileum with stricture. Ustekinumab dosing was increased to q4weeks, azathioprine was initiated, and he underwent stricturoplasty. Follow-up ileoscopy three months later revealed two ulcers in the neo- TI (Figure 1). Vedolizumab q8weeks was initiated in addition to ustekinumab q4weeks and azathioprine 125mg. After four months on this regimen the patient felt better, but follow-up ileoscopy showed two persistent ulcers in the neo-TI. Vedolizumab dosing interval was increased to q4weeks. After four months, subsequent ileoscopy demonstrated normal neo-TI (Figure 2). Histologic evaluation of biopsies confirmed deep remission of crohn’s disease. No adverse side effects have occurred with maximum doses of both ustekinumab and vedolizumab combination therapy. Discussion This case supports both the safety and efficacy of ustekinumab and vedolizumab dual biologic therapy for treatment of severe, refractory Crohn’s disease. While there are reports of DBT inducing clinical remission, this case supports efficacy for vedolizumab and ustekinumab combination therapy to induce deep histologic remission. Large practical clinical trials are needed to better investigate the safety and efficacy of DBT with vedolizumab and ustekinumab, but our case suggests this combination may be a safe and efficacious therapy for refractory CD patients.

scholarly journals The Comparison of Hypomethylating Agents (HMA) Monotherapy with HMA Combined with Intensive Chemotherapy for Intermediate / High-Risk MDS or AML

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3903-3903
Author(s):  
Jiang Ji ◽  
Zhao Wang ◽  
Bing Han
Keyword(s):  
High Risk ◽  
Combination Therapy ◽  
Death Rate ◽  
Therapy Group ◽  
Meta Analysis ◽  
Combination Group ◽  
Combination Therapy Group ◽  
Hypomethylating Agents ◽  
Monotherapy Group ◽  
Significant Difference

Introduction: Hypomethylating agents (HMA) azacitidine and decitabine were the first-line therapy for intermediate/ higher-risk myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) patients unsuitable for hematopoietic cell transplantation (HSCT). HMA combined with chemotherapy was recently used to achieve for a better outcome. However, few studies were carried out to compare the HMA monotherapy to the HMA and chemotherapy combination therapy. This meta-analysis aimed to compare the efficacy, survival benefit and safety of HMA monotherapy and combination therapy (with chemotherapy) in patients with intermediate/high-risk MDS or AML. Methods: Related articles published between January 2009 and April 2019 were selected and patients were separated as monotherapy group and combination group for meta-analysis. To further eliminate the potential influence of differences in patients' baseline characteristic between the two groups, subgroups with similar patients' baseline characteristics were selected for further analysis. Complete response (CR) rate, overall response (ORR) rate, 1-year overall survival (OS) rate, 1-month death rate and the proportion of adverse event (AE) were pooled and compared. Results: 13 RCT or cohort studies with 997 patients (790 in monotherapy group, 207 in HMA combination group) were selected for meta-analysis. For the pooled data, there was no significant difference in sex and cytogenetic risk between the 2 groups, but the age of combination therapy group was significantly younger than that of the monotherapy group (61.3±13.2 year-old vs 67.7±10.2 year-old, p=0.000). The CR and ORR rate were significantly higher in combination therapy group (53% vs 17%, p=0.000 for CR and 67% vs 44%, p=0.000 for ORR). However, the 1-year OS (56% for combination therapy vs 51% for HMA monotherapy group, p=0.282) and 1-month death rate (5% for combination therapy vs 4% for HMA monotherapy group, p=0.965) were similar between the two groups. The incidence of CTCAE grade 3-4 infection and bleeding were significantly higher (infection: 50% for combination therapy vs 25.7% for monotherapy group, p=0.003; bleeding: 27.5%% for combination therapy vs 7.8% for monotherapy group, p=0.004) in combination group. In subgroup analysis, 117 and 179 patients were included in combination group and HMA monotherapy group, respectively. There was no significant difference in age (69.5±4.6 vs 69.0±6.8 years old, p=0.451) and proportion of favorable/intermediate cytogenetic risk (62% vs 71%, p=0.114) between the two groups, but a significantly lower proportion of male was found in combination therapy group (57% vs 74%, p=0.003). Although combination group had a higher CR rate (49% vs 17%, p=0.000), it had similar ORR rate (58% vs 49%, p=0.140) to monotherapy group. Meanwhile, combination therapy came with higher 1-month death rate (12% vs 3%, p=0.008) and lower 1-year OS (54% vs 68%, p=0.013) compared with monotherapy group. Conclusions: HMA combined with chemotherapy could increase CR rate in all patients and ORR rate in younger patients, but could not improve OS. For patients with similar older age, combination therapy could result in higher 1-month death rate and less 1-year OS. Disclosures No relevant conflicts of interest to declare.

scholarly journals Methotrexate for the Treatment of Pediatric Crohn’s Disease: A Systematic Review and Meta-analysis

2018 ◽  
Vol 24 (10) ◽  
pp. 2135-2141 ◽  
Author(s):  
Ruben J Colman ◽  
Rachel C Lawton ◽  
Marla C Dubinsky ◽  
David T Rubin
Keyword(s):  
Systematic Review ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Combination Therapy ◽  
Treatment Efficacy ◽  
Clinical Remission ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Free Text ◽  
Pediatric Ibd

Abstract Background Methotrexate (MTX) is an immunomodulator used for the treatment of pediatric inflammatory bowel disease (IBD). There are currently no RCTs that assess the treatment efficacy of methotrexate within the pediatric IBD patient population. This systematic review and meta-analysis assesses the efficacy of MTX therapy among the existing pediatric literature. Methods A systematic literature search was performed using MEDLINE and the Cochrane library from inception until March 2016. Synonyms for ‘pediatric’, ‘methotrexate’ and ‘IBD’ were utilized as both free text and MESH search terms. The studies included contained clinical remission (CR) rates for MTX treatment of pediatric IBD patients 18 yrs old, as mono- or combination therapy. Case studies with <10 patients were excluded. Quality assessment was performed with the Newcastle-Ottawa Scale. Meta-analysis calculated pooled CR rates. A random-effects meta-analysis with forest plots was performed using R. Results Fourteen (11 monotherapy, 1 combination therapy, 2 both; n = 886 patients) observational studies were eligible out of 202 studies. No interventional studies were identified. The pooled achieved CR rate for pediatric CD patients on monotherapy within 3-6 months was 57.7% (95% CI 48.2-66.6%), (P =0.22; I2 = 29.8%). The CR was 37.1% (95% CI 29.5-45.5%), (P = 0.20; I2 = 37.4%) for maintenance therapy at 12 months. Sub-analysis could not identify CR differences between MTX administration types, thiopurine exposure. Conclusions This meta-analysis demonstrated that, over 50% of pediatric Crohn’s disease patients induced with methotrexate achieved clinical remission, while 12-month remission rate was only 37%. Prospective controlled interventional trials should assess treatment efficacy among patient subgroups.

Risk Versus Benefit of Combined Aspirin and Warfarin Therapy in Patients With Atrial Fibrillation

2020 ◽  
pp. 089719002091663
Author(s):  
Tara A Nagaraj ◽  
Melissa J. Snider ◽  
Erica Davidson ◽  
Raul Weiss ◽  
Junan Li ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Combination Therapy ◽  
Major Bleeding ◽  
Therapy Group ◽  
Stable Coronary Artery Disease ◽  
Group Versus ◽  
Bleeding Risk ◽  
Combination Group ◽  
Monotherapy Group ◽  
Significant Difference

Purpose: Guidelines have differing recommendations for aspirin use in patients with an indication for anticoagulation. The purpose of this study was to evaluate the incidence of major bleeding and thromboembolic events (TEs) in patients with atrial fibrillation (AF) receiving warfarin alone (monotherapy group) versus warfarin plus aspirin (combination therapy group). Methods: This was a retrospective, cohort study including patients from a pharmacist-run anticoagulation clinic. Inclusion criteria were patients with AF receiving anticoagulation between January 2013 and January 2014 observed over 5 years. Results: One hundred forty-two patients were included in the combination group versus 89 in monotherapy group. In the combination group, 60 (42.3%) patients were on aspirin for no apparent indication, 19 (13.4%) had stable coronary artery disease and diabetes, and 26 (18.3%) had diabetes alone. Major bleeding occurred in 21 (14.9%) patients in the combination group versus 7 (7.9%) patients in the monotherapy group (odds ratio [OR] = 2.02, 95% confidence interval [CI]: 0.78-5.91; P = .17). TE occurred in 10 (7%) patients in the combination group versus 4 (4.5%) in the monotherapy group (OR = 1.61, 95% CI: 0.44-7.24; P = .57). There was no significant difference in bleeding ( P = .85) or TE ( P = .37) rates between aspirin indications in the combination group. Conclusion: Combination therapy versus monotherapy may increase bleeding risk with little benefit in decreasing AF-related stroke or cardiovascular events.

scholarly journals 204. Clinical Outcomes with Ceftaroline Monotherapy versus Daptomycin-Ceftaroline Combination Therapy in the Treatment of Methicillin-Resistant Staphylococcus aureus Bacteremia

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S209-S210
Author(s):  
Gabriela Andonie ◽  
Elizabeth O Hand ◽  
Kelly R Reveles ◽  
Kristi A Traugott
Keyword(s):  
Staphylococcus Aureus ◽  
Combination Therapy ◽  
Clinical Outcomes ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Controlled Trial ◽  
Primary Source ◽  
Retrospective Chart Review ◽  
Combination Group ◽  
Methicillin Resistant ◽  
Significant Difference

Abstract Background Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is associated with poor outcomes and increased mortality. Daptomycin (DAP) and ceftaroline (CPT) in combination has been explored as a potential treatment option and showed improved outcomes compared to vancomycin/standard therapy. CPT monotherapy has been evaluated as salvage therapy for MRSA bacteremia but, to our knowledge, not as a comparator to DAP-CPT combination therapy. The purpose of this study is to compare the clinical outcomes of DAP and CPT combination therapy to CPT monotherapy in the setting of MRSA bacteremia. Methods A retrospective chart review of adult patients (≥ 18 years of age) admitted to University Health from January 2017 to December 2020 with a diagnosis of MRSA bacteremia was performed. Patients received either CPT monotherapy or DAP-CPT combination therapy for a minimum of 48 hours during their course of therapy. Results Thirty-two patients met inclusion criteria and were evaluated. Primary source of infection was pulmonary in the CPT monotherapy group (n=7/24; 29.2%) and osteomyelitis in the DAP-CPT combination group (n= 4/8; 50.0%). Median duration of bacteremia was 8 days and 9 days in the CPT monotherapy and DAP-CPT combination group, respectively. Microbiological cure was achieved in 95.8% (n=23/24) of patients in the CPT monotherapy and 100% (n=8/8) of patients in the DAP-CPT combination group. Bacteremia relapse (30 day, p=0.62; 60 day, p=0.63), readmission rates (30 day, p=0.62; 60 day, p=0.63), and mortality rates (30 day, p=0.70; 90 day, p=0.85) were similar in both groups. There was no statistically significant difference in safety parameters, including incidence of acute kidney injury (p=1.00) and creatine kinase elevations (p=1.00). Bone marrow suppression after at least 72 hours of therapy, including anemia, leukopenia, and thrombocytopenia, was also not statistically significant between groups. Conclusion This study was unable to find a statistically significant difference in clinical outcomes between patients receiving CPT monotherapy or DAP-CPT combination therapy. A large prospective, randomized controlled trial to assess CPT monotherapy and DAP-CPT combination therapy for the treatment of persistent MRSA bacteremia is warranted. Disclosures All Authors: No reported disclosures

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