Subject(s)
Drug Storage/methods , Inflammatory Bowel Diseases , Patient Compliance , Biological Availability , Biological Factors/administration & dosage , Biological Factors/economics , Biological Factors/pharmacokinetics , Drug Costs , Humans , Injections, Subcutaneous , Temperature , Time FactorsABSTRACT
BACKGROUND: In Australia, infliximab (IFX) and adalimumab (ADA) are available for the treatment of moderate-severe Crohn disease (CD) refractory to conventional therapies, with minimal local data comparing their efficacy. AIM: The aim of this study was to compare clinical and biochemical outcomes at 3 and 12 months between patients receiving induction and maintenance therapy with IFX versus ADA. METHODS: Retrospective single-centre audit of all patients commenced on IFX or ADA as their first anti-tumour necrosis factor agent between July 2007 and May 2012. Clinical and biochemical parameters were compared pre-commencement, 3 and 12 months post-commencement. RESULTS: A total of 81 patients was included in the study; 63 IFX-treated and 18 ADA-treated. Significant Crohn disease activity index (CDAI) reductions were noted within both groups at 3 months (P < 0.001) and 12 months (P < 0.001). Similarly, significant reductions were noted in steroid doses within groups at 3 months (P < 0.05) and 12 months (P < 0.05), with notable reductions in C-reactive protein (CRP) at 3 months within groups (P < 0.05). Adverse events occurred in 14.3% of IFX and 11.1% of ADA patients. Comparing IFX with ADA, no difference was shown between groups in CDAI reductions at 3 months (P = 0.94) and 12 months (P = 0.95), steroid dosing at 3 months (P = 0.23) and 12 months (P = 0.81), and CRP reduction at 3 months (P = 0.33) and 12 months (P = 0.62). Fistula-related admissions were significantly reduced in IFX patients (100% reduction post-IFX vs 66.7% post-ADA) (P = 0.01). CONCLUSION: Clinical and biochemical outcomes were similar in patients treated with IFX or ADA as induction and maintenance therapy for CD. However, significant reductions were noted in admissions relating to fistulising disease in IFX patients.
Subject(s)
Adalimumab/administration & dosage , Anti-Inflammatory Agents/administration & dosage , Crohn Disease/drug therapy , Infliximab/administration & dosage , Adult , Antibodies, Monoclonal, Humanized/therapeutic use , Australia , C-Reactive Protein/analysis , Female , Humans , Male , Middle Aged , Remission Induction , Retrospective Studies , Time Factors , Treatment Outcome , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Young AdultABSTRACT
BACKGROUND: 'Dose tailoring' of anti-tumour necrosis factor alpha (TNF-α) therapy in Crohn disease (CD), by dose escalation, or shortening of dosing intervals, has been suggested to regain clinical response following a flare in a proportion of patients. However, reported outcome data are sparse and none exists from Australia. METHOD: In an observational multicentre, retrospective study, the impact of anti-TNF-α dose tailoring on corticosteroid use, the need for surgery and physician perception of clinical efficacy was examined in a real-world setting at six Australian adult teaching hospitals. Demographics, disease characteristics, medications, indication for and duration of dose tailoring were documented. RESULTS: Fifty-five CD patients were identified as requiring dose tailoring and secondary loss of response was the indication in 96%. Either adalimumab (64%) or infliximab (36%) was dose escalated for a median of 5 months (range 1-47), with a median of 20 months follow up (range 3-65). At 3 months, dose tailoring reduced the mean number of days on high-dose corticosteroids (45 vs 23, P = 0.01). Most (78%) patients remained resection free, and 73% of physicians reported good clinical efficacy of dose tailoring. Of those who de-escalated therapy due to induction of remission, long-term (>12 months) follow up and complete data on steroid use were available in 15/28, with 12/15 (80%) remaining steroid free at 1 year. CONCLUSION: Short-term dose tailoring regains disease response in the majority of patients with CD. Of these, most will remain free of corticosteroids at 1 year after de-escalating therapy.
Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal/administration & dosage , Crohn Disease/diagnosis , Crohn Disease/drug therapy , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Adalimumab , Adolescent , Adrenal Cortex Hormones/administration & dosage , Adult , Aged , Analysis of Variance , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal, Humanized/adverse effects , Australia , Cohort Studies , Confidence Intervals , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Follow-Up Studies , Humans , Infliximab , Logistic Models , Male , Maximum Tolerated Dose , Middle Aged , Remission Induction/methods , Retrospective Studies , Risk Assessment , Severity of Illness Index , Tertiary Care Centers , Treatment Outcome , Young AdultABSTRACT
Lymphocyte count, lymphocyte subpopulations identified by monoclonal antibodies and mitogen stimulation assays with phytohaemagglutinin, concanavalin A, pokeweed mitogen and staphylococcal protein A, were used to quantitate the effect of methotrexate on the immune response in children with acute lymphatic leukaemia on maintenance therapy. Methotrexate exerted a profound but apparently short-term effect on these parameters as it is prescribed in current maintenance schedules for childhood acute lymphatic leukaemia. A significant drop in lymphocyte count, affecting all subpopulations, was observed 4 h after oral or intramuscular administration of methotrexate which had reverted to pre-methotrexate values one week after the drug was given. Lymphocyte function was markedly affected, with a major decrease in mitogen responsiveness 1 h after methotrexate and a reversion to pre-methotrexate values by 48 h. A selectivity of suppressor T cells to methotrexate is proposed as being responsible for early recovery. Scheduling of methotrexate in current maintenance programmes would therefore appear to allow adequate time for recovery of immunoresponsiveness between doses.
