Certolizumab pegol, a monthly subcutaneously administered Fc-free anti-TNFalpha, improves health-related quality of life in patients with moderate to severe Crohn's disease.
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ABSTRACT:
SUBMITTER: Rutgeerts P
PROVIDER: S-EPMC2225995 | biostudies-other | 2008 Mar
REPOSITORIES: biostudies-other
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Project description:Adherence to antipsychotic medications is a major challenge in schizophrenia. Long-acting injectable antipsychotics have been shown to offer advantages over oral formulations. A new extended release formulation of risperidone for subcutaneous injection was developed to address issues of non-adherence. The aim of this manuscript was to compare the new subcutaneous formulation to currently available formulations of injectable risperidone and paliperidone to determine whether the novel delivery by subcutaneous injection may provide substantial benefits. A literature search was conducted using PubMed, OVID, and Cochrane Library electronic databases to assess the advantages and disadvantages of long-acting formulations of risperidone. Potential advantages of risperidone for subcutaneous injection include a simplified dosing and ease of administration. Potential disadvantages include injection site pain and medication cost.
| S-EPMC7053417 | biostudies-literature
Project description:Therapeutic options in development for the treatment of Crohn's disease represent a broad range of approaches to this complex disease. This active pipeline contains a combination of both small-molecule entities and targeted monoclonal antibodies.
| S-EPMC5969213 | biostudies-other
Project description:IntroductionIn patients with moderate to severe Crohn's disease (CD), intravenous induction and subcutaneous maintenance dosing with risankizumab was efficacious and well tolerated. Long-term management of CD via self-administration of risankizumab using an on-body injector (OBI) may improve treatment adherence through convenience and ease of use.MethodsWithin the FORTIFY maintenance study, 46 patients from the United States (US) sites participated in an open-label extension Substudy and received 180 mg or 360 mg risankizumab delivered subcutaneously via OBI [360 mg (2.4 mL, 150 mg/mL) or 180 mg (1.2 mL, 150 mg/mL)]. At the Week 0 visit, patients were trained (pre-injection) by site staff, using Instructions for Use (IFU) and a training video, to self-administer risankizumab at Weeks 0 (on site), 8 (at home), and 16 (on site). Key objectives of the Substudy 4 were to assess OBI usability (observer rating of successful self-administration), hazard-free self-injection at Weeks 0 and 16, and patient rating of acceptability using the Self-Injection Assessment Questionnaire (SIAQ) at Weeks 0, 8, and 16. Additionally, the proportion of patients in clinical remission (CD Activity Index < 150) was collected at Weeks 0 and 16.ResultsAll patients successfully self-administered risankizumab via OBI, including two patients who successfully self-administered with a second OBI (i.e., required two injection attempts). Acceptability of self-injection was high. Two patients (n = 2) experienced a use-related hazard. Stable clinical remission was observed with both risankizumab doses. Two patients experienced injection site reactions; neither was related to the OBI per investigator's assessment. Two device-related adverse events related to topical adhesive reactions were reported, both mild and resolved. No new safety risks were observed.ConclusionThe efficacy and safety of maintenance risankizumab delivered via OBI and OBI usability support the use of this device in patients with moderate to severe CD.Trial registrationClinicalTrials.gov identifiers NCT03105102 (FORTIFY).
| S-EPMC10011765 | biostudies-literature
Project description:IntroductionIn the phase 2 CELEST study, positive efficacy results were obtained with the Janus kinase 1 inhibitor upadacitinib for adult patients with moderate to severe Crohn's disease. We present the health-related quality of life and work productivity improvement results with upadacitinib from CELEST.MethodsCELEST (NCT02365649) was a double-blind study where patients were randomized 1:1:1:1:1:1 in the 16-week induction period to placebo or upadacitinib 3 mg twice daily (BID), 6 mg BID, 12 mg BID, 24 mg BID, or 24 mg once daily (QD). Patients completing the induction period were re-randomized 1:1:1 to receive upadacitinib 3 mg BID, 12 mg BID, or 24 mg QD for 36 weeks or 3 mg BID, 6 mg BID, or 12 mg BID (after amendment). Inflammatory Bowel Disease Questionnaire (IBDQ), European Quality of Life-5 Dimensions visual analog scale (EQ-5D VAS), and Work Productivity and Activity Impairment (WPAI) questionnaire outcomes were assessed at baseline and Weeks 8, 16, and 52.ResultsAt Week 16, a significant percentage (P ≤ 0.05) of patients receiving upadacitinib 6-mg BID dose or higher achieved IBDQ response (IBDQ score change ≥ 16 points; 49%-57% for upadacitinib vs. 24% for placebo) and IBDQ remission, except 24 mg QD (IBDQ score ≥ 170; 26%-39% for upadacitinib vs. 11% for placebo). Greater improvements in IBDQ total score, EQ-5D VAS, and activity impairment from baseline (P ≤ 0.1) versus placebo were also observed. Larger improvements (P ≤ 0.1) in IBDQ response and total score and EQ-5D VAS were observed at Week 8 with 6 and 24 mg BID versus placebo, with improvements for all dosages maintained or greater at Week 52 for IBDQ, EQ-5D VAS, and WPAI endpoints, in particular for the 12-mg BID group.ConclusionImprovements in health-related quality of life and work productivity were achieved and sustained with upadacitinib in patients with moderate to severe Crohn's disease.Trial registrationClinicalTrials.gov identifier, NCT02365649.
| S-EPMC8107073 | biostudies-literature
Project description:OBJECTIVE:To evaluate open-label adalimumab therapy for clinical effectiveness, fistula healing, patient-reported outcomes and safety in Canadian patients with moderate to severe Crohn's disease (CD) who were either naive to or previously exposed to antitumour necrosis factor (anti-TNF) therapy. METHODS:Patients with moderate to severe CD (CD activity index [CDAI] score of greater than 220, or Harvey-Bradshaw index [HBI] of 7 or greater) were eligible. Patients received open-label adalimumab as induction (160 mg and 80 mg subcutaneously [sc]) at weeks 0 and 2, respectively and maintenance (40 mg sc every other week) therapy. At or after eight weeks, patients with flare or nonresponse could have their dosage increased to 40 mg sc weekly. Patients were followed for a minimum of six months or until adalimumab was commercially available in Canada. RESULTS:Of the 304 patients enrolled, 160 were infliximab experienced, while 144 were anti-TNF naive. HBI remission (HBI score of 4 or lower) at week 24 was achieved by 53% of anti-TNF-naive and 36% of infliximab-experienced patients (P<0.01; P<0.001 for both groups for all visits versus baseline). Fistula healing rates at week 12 were 48% for anti-TNF-naive patients, and 26% for infliximab-experienced patients. At week 24, fistula healing rates were significantly greater for the anti-TNF-naive group (60% versus 28%; P<0.01). Improvements in quality of life and work productivity were sustained from week 4 to week 24 for all patients. Serious infections occurred in 2% of patients. CONCLUSIONS:Adalimumab therapy induced and sustained steroidfree remission in both infliximab-experienced and anti-TNF-naive patients with moderate to severe CD. Clinically meaningful rates of fistula healing were also observed. Improvements in patient-reported outcomes were sustained throughout the 24-week study period.
| S-EPMC3186726 | biostudies-literature
Project description:Background and objectivesA multi-centre, non-comparative study examining the efficacy and safety of Subgam, a normal immunoglobulin (IgG) given weekly as a rapid subcutaneous infusion to patients with primary immune deficiency (PID), is reported. Also included is a summary of adverse drug reactions associated with the use of marketed Subgam in the UK.Materials and methods50 patients with stable PID on IgG therapy were enrolled: Stage 1 included three infusions with prior IgG product followed by 6 months with Subgam, Stage 2 involved long-term Subgam therapy up to 4 years.ResultsStage 1, 85% of the subjects aged >12 years and 93% of the subjects aged <12 years achieved IgG levels ≥6 and ≥4 g/L, respectively at all observations. There were 3.62 infections/patient/year during Subgam treatment. The most common product-related events were infusion site reactions (50% of patients). Recent post-hoc pharmacokinetics analysis of the post-infusion serum total IgG concentration indicated that the mean dose-normalised incremental IgG AUCτ following intravenous dosing (120.5 g.day/L) was 1.64-fold that of the dose-normalised mean incremental IgG AUCτ following subcutaneous dosing (73.6 g.day/L), corresponding to an estimated IgG bioavailability for subcutaneous dosing of 61%. Only 34 post-licensing adverse reactions have been received in 30 patients over a period of 10 years; fourteen were classed as serious as defined by the ICH guidelines on good clinical practice. The most common post-licensing adverse reaction was infusion site reaction (7 reports). There were 7 reports of flu-like symptoms (pyrexia/shivering/rigors/feeling hot or cold), 2 other reports of combined flu-like symptoms and infusion site reactions, 5 reports of generalised skin reactions, and 3 reports of combined infusion site and skin reactions. There were also reports of anaphylaxis (2 reports) and 8 other adverse events (including headache). In conclusion, Subgam is effective and well tolerated in the treatment of PID.Trial registrationClinicalTrials.gov NCT02247141.
| S-EPMC4519338 | biostudies-literature
Project description:The advent of anti-tumor necrosis factor (TNF)-? therapy has been a major advance in the medical management of Crohn's disease (CD). However, a significant proportion of patients with CD do not respond adequately to treatment with these agents. Primary and secondary nonresponse to anti-TNF? therapy represents a common clinical challenge, and highlights the need for the development of additional medication options for CD. The proinflammatory cytokines interleukin (IL)-12 and IL-23 are thought to play a key role in the pathogenesis of CD, and serve as a potential target for additional biologic therapies. Monoclonal antibodies targeting IL-12/23 have shown efficacy in animal models of colitis, and are currently being studied in Phase III clinical trials of CD. This review focuses on ustekinumab, a fully human immunoglobulin G1 monoclonal antibody, which blocks activity of IL-12 and IL-23 through binding the p40 subunit, and describes the current efficacy and safety data for ustekinumab in patients with CD.
| S-EPMC4041179 | biostudies-other
Project description:Plasma pharmacokinetic profiles and the anti-inflammatory efficacy of meloxicam were determined when administered subcutaneously (SC) or intramuscularly (IM) to sheep. Merino ewes were initially injected with 0.1 mL of oil of turpentine into a forelimb to induce inflammation, followed by either 1.0 mg/kg or 2.0 mg/kg of meloxicam administered either SC or IM (n = 6 per treatment group) or followed by no meloxicam administration (control) (n = 4). Ewes were examined to determine skin temperature, limb circumference, limb sensitivity and signs of lameness at 0, 0.5, 1, 2, 4, 6, 8, 10, 12, 24 and 48 h following treatment, with blood collected at these time-points to quantify meloxicam plasma concentrations. Skin temperature of ewes dosed with meloxicam at 1.0 mg/kg SC and 2.0 mg/kg IM at 12 h and 1.0 mg/kg SC at 24 were significantly different to the controls (P < 0.05). Limb circumferences of ewes dosed with 1.0 mg/kg IM were significantly different to controls at 10 h and 12 h (P < 0.05). All meloxicam treatment groups resulted in reduced limb sensitivity compared to controls at 6 h, with the 1.0 and 2.0 mg/kg IM treatments significantly different at 12 h (P < 0.05) and 1.0 and 2.0 mg/kg SC groups, significantly different to controls at 48 h (P < 0.05). No significant difference in lameness scores were detected over 48 h. The 1.0 mg/kg IM treatment had a significantly greater plasma meloxicam concentration than the 1.0 mg/kg SC treatment over 0.5 to 4 h (P < 0.001). Both 1.0 mg/kg SC and IM treatments demonstrated elimination half-lives (mean ± SD) of 10.82 ± 2.46 and 12.63 ± 2.37 h, respectively. Meloxicam at all doses provided some anti-inflammatory and analgesic effects from 6 to 48 h; however no route could be distinguished as more efficacious than the others.
| S-EPMC6481916 | biostudies-literature
Project description:IntroductionTo compare the cost-effectiveness of vedolizumab with that of conventional therapy in patients with moderate-to-severe active Crohn's disease (CD) in China.MethodsA decision tree and Markov model were built to predict the lifetime cost and health outcomes in the induction phase and maintenance phase of vedolizumab treatment and conventional therapy (a combination of corticosteroids, immunosuppressants, and aminosalicylates) in adult patients with moderate-to-severe active CD from the perspective of China's healthcare system. Clinical efficacy and health utility were derived from the GEMINI 2 and GEMINI 3 trials and published literature. Costs were mainly obtained from clinical physician surveys in China and are presented in 2020 US dollars. Health outcomes (quality-adjusted life years, QALYs) and costs were discounted at an annual rate of 5%. The incremental cost per QALY gained was used to compare the cost-effectiveness of the two treatments. One-way and probabilistic sensitivity analyses (PSAs) were performed to test the robustness of the model.ResultsThe model predicted more QALYs (9.92 vs 9.00 QALYs) and lower incurred costs ($288,284 vs $309,680) in vedolizumab than in conventional therapy in a mixed population (anti-TNF-naïve and anti-TNF-failure populations) over a lifetime horizon in the base-case analysis. Similar results were observed in the anti-TNF-naïve and anti-TNF-failure subgroups of patients with CD. One-way sensitivity analysis results suggested that health state cost was the most influential factor in the model. The PSA results supported the dominance of vedolizumab in the base-case analysis.ConclusionVedolizumab appears to be a cost-effective strategy option in the treatment of adult patients with moderate-to-severe active CD in China in both anti-TNF-naïve and anti-TNF-failure populations.
| S-EPMC8342392 | biostudies-literature
Project description:IntroductionAtopic dermatitis (AD) is a chronic inflammatory skin disease for which signs and symptoms have a negative impact on a patient's quality of life (QoL) and mental health. Here, we assess the impact of lebrikizumab on QoL and mental health after 16 weeks of treatment in patients with moderate-to-severe AD.MethodsData were analyzed over 16 weeks from two separate phase 3, randomized, placebo-controlled, monotherapy trials (ADvocate1 and ADvocate2). Patient-reported outcomes were assessed using the following measures: Dermatology Life Quality Index (DLQI), EQ-5D-5L visual analogue scale (VAS), EQ-5D-5L index scores (UK and US), Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety, and PROMIS Depression.ResultsTreatment with lebrikizumab 250 mg every 2 weeks in two studies led to statistically significant improvements (based on nominal p values) versus placebo in DLQI since week 4 (the first timepoint assessed) for the following measures: change from baseline in DLQI total score (ADvocate1 - 7.8 vs - 2.8; ADvocate2 - 7.3 vs - 3.9), proportion of patients with DLQI ≥ 4-point improvement (ADvocate1 69.5% vs 36.2%; ADvocate2 60.5% vs 42.6%), DLQI total score ≤ 5 (ADvocate1 36.7% vs 8.8%; ADvocate2 29.6% vs 10.8%), and DLQI (0, 1) (ADvocate1 12.3% vs 1.7%; ADvocate2 9.2% vs 1.7%). Improvements in DLQI measures, EQ-5D-5L index scores (UK and US), and EQ-5D-5L VAS were sustained through week 16. Additionally, lebrikizumab improved PROMIS Anxiety and PROMIS Depression scores, and improvements were higher in patients with at least a mild score (≥ 55) versus placebo for PROMIS Anxiety (ADvocate1 - 7.43 vs - 1.51; ADvocate2 - 4.95 vs - 0.82) and PROMIS Depression (ADvocate1 - 7.42 vs - 2.46; ADvocate2 - 4.28 vs - 2.00).ConclusionsTreatment with monotherapy 250 mg lebrikizumab for 16 weeks provided clinically meaningful improvements in outcomes related to QoL and mental health for patients with moderate-to-severe AD. Lebrikizumab-treated patients reported improvements in DLQI as early as week 4, the first measure since baseline.Trial registrationClinicalTrials.gov Registration NCT04146363 (ADvocate1) and NCT04178967 (ADvocate2).
| S-EPMC11265048 | biostudies-literature