Weeks Of Adalimumab Research Articles

EE653 Efficacy of Targeted Drugs for the Treatment of Adults With Moderate-to-Severe Plaque Psoriasis in the Russian Federation: Number Needed to Treat and Costs Per Responder

To reassess the number of adults with moderate-to-severe plaque psoriasis needed to treat (NNT) to achieve one Psoriasis Area and Severity Index (PASI) 75/90 response and costs per responder (CpR) after 12 weeks for adalimumab (ADA), infliximab (INF), etanercept (ETN), ixekizumab (IXE), netakimab (NTK), secukinumab (SEC), ustekinumab (UST), tofacitinib (TOFA), and apremilast (APR) and after 16 weeks for certolizumab pegol (CZP), risankizumab (RIS) and guselkumab (GUS) and 1 year of therapy for each drug analyzed.

Analysing cord blood levels of TNF inhibitors to validate the EULAR points to consider for TNF inhibitor use during pregnancy

BackgroundTo minimise placental transfer of tumour necrosis factor inhibitors (TNFi), the European League Against Rheumatism (EULAR) created points to consider (PtC) for the use of TNFi during pregnancy. We are...

Vascularization and fibrosis are important ultrasonographic tools for assessing response to adalimumab in hidradenitis suppurativa: Prospective study of 32 patients.

Hidradenitis suppurativa (HS) is a debilitating skin disease presenting with nodules, abscesses, and fistulae preferentially in the main folds. Adalimumab is the only licensed biologic for moderate-to-severe HS. Ultrasound demonstrated good sensitivity to provide anatomic and functional information in HS; in particular assessing vascularization, related to inflammation, and fibrosis in HS lesions before and after adalimumab treatment with ultrasound and Color Doppler may integrate clinical evaluation with imaging. Patients with moderate-to-severe HS were enrolled in this observational prospective study. Clinical evaluation (according to Hurley classification and International Hidradenitis Suppurativa Severity Score System score) and ultrasound (according to US HS-PGA)/Color Doppler were performed at baseline and after 12 weeks of adalimumab. Ultrasound was used for assessing fibrosis and Color Doppler for vascularization. For each patient, the three most severe lesions among abscesses and fistulae were chosen for total 96 lesions. Thirty-two patients were included, 18 men (56%) and 14 women (44%) with mean age 41.2. Mean IHS4 was 22.4 at baseline and dropped to 14.7 at week 12. Based on US HS-PGA, 14 out of 32 patients fell down by one or more classes of severity. Interestingly, adalimumab led to overall decrease in vascularization, particularly in lesions with intense vascular flow, which were 78 (81.3%) at baseline and became only 25 (26.04%). Finally, marked increase in fibrosis was seen after adalimumab, notably in lesions without fibrosis, which were 81 (84.4%) at baseline and became 15 (15.6%). This study confirms the efficacy of adalimumab in HS and provides value for vascularization and fibrosis as important ultrasonographic tools integrating clinical scores.

P495 Spacing the administration interval of anti-TNF agents: a valid strategy for patients with inflammatory bowel disease?

Patients with psoriasis and rheumatologic diseases are eventually treated with biological agents using treatment schedules with more spaced administrations than those approved. These schedules are cheaper and they even might reduce the risk of adverse events. However, these treatment strategies are scarcely used in inflammatory bowel disease (IBD). Aim: Two evaluate the clinical course of IBD patients treated with anti-TNF agents by means of a spacing strategy (administration interval greater than 8 weeks for infliximab or 2 weeks for adalimumab). Using the local databases from two referral centres, all the patients with IBD who were treated with infliximab or adalimumab by means of a spacing strategy, were identified. Patients with ostomy or ileoanal pouch, indication of anti-TNF therapy for perianal disease, or adverse events as the main cause for spacing strategy, were excluded. The spacing strategy success was considered if at the end of the follow-up the patient remained in clinical remission with the same spaced schedule or without biological therapy and if no return to the conventional schedule, dose-escalation, switch, swap, a course of systemic corticosteroids or surgery were required. Eighty-five patients were included (58 Crohn’s disease, 27 ulcerative/IBD unclassified). Sixty were treated with infliximab (49 every 10 weeks and 11 every 12 weeks) and 25 patients with adalimumab every 3 weeks. Prior to the index course of anti-TNF, 38% of patients followed a previous course of anti-TNF, and 7% required dose-escalation. The spacing schedule was initiated after the median of 25 months of anti-TNF treatment (IQR 14–49). Thirty-seven per cent had ileocolonoscopy (3% with endoscopic activity) and 17% MRI enterography (29% with RM activity) within 6 months before spacing began. 60% of patients were on concomitant immunomodulatory treatment at the beginning of spacing. The median time on spacing schedule was 15 months (IQR 12–25). Thirty-seven per cent of patients returned to a conventional schedule and 9% required dose-escalation. In 22 patients (26%) the anti-TNF was stopped because of sustained remission (9/22), clinical relapse (3/22), adverse events (2/22) or for other reasons (3 pregnancy, 3 neoplasia, 2 other). At the end of follow-up, 50 out of 85 patients (59%) met the success criteria of the spacing strategy. No baseline characteristics were found to be associated with success. Anti-TNF administration at longer intervals than the ones provided in the data sheet of the drug can be a convenient, safe, useful and cheaper alternative for IBD patients, even though, at this time, we do not have predictors of success.

Dramatic Effect of Tofacitinib on TNF-Inhibitor Resistant Synovitis: A Case Report

A 58-year-old woman with a 2.5-year history of rheumatoid arthritis showed a pain, severe swelling, and a decreased range of motion of left knee joint. Medical therapy with 8 mg per week of oral methotrexate and 1 mg per day of tacrolimus in combination with 40 mg per 2 weeks of adalimumab failed to control the disease activity. Administration of tofacitinib achieved the successful disease control, and MRI taken 5 months after the initiation of tofacitinib showed the disappearance of synovial mass within the knee joint and the bone marrow oedema and marked reduction of the popliteal cyst. The use of tofacitinib for inadequate response to the first TNF inhibitor as a third-line DMARD showed dramatic effect on severe synovitis, and the patient could avoid the surgical intervention.

Lengthening the time intervals between doses of biological agents in psoriatic arthritis patients: A single-center retrospective study.

Anti-tumor necrosis factor (TNF) alpha therapy has changed the course of psoriatic arthritis (PsA), but clinical experience about lengthening of time intervals between drug administrations is still limited. The aims of the study were to evaluate: (1) the long-term efficacy (over a 4-year period) of etanercept/adalimumab in a subset of PsA patients who did not require switches; and (2) the progressive lengthening of time intervals between treatments in patients who achieved minimal disease activity (MDA). PsA outpatients attending the Rheumatology Clinic-University of Padova who took a single anti-TNF agent (etanercept/adalimumab) for a 4-year period were studied. Therapy efficacy was assessed using clinical, biochemical, and disease activity (DA) indexes. The intervals between treatments were empirically and progressively lengthened after MDA was reached and maintained. One hundred and forty-one patients (mean age, 51.22 ± 12.34 years; mean disease duration, 12.1 ± 8.42 years) treated with etanercept/adalimumab (47.5% and 52.5%, respectively) were studied. DA indexes showed a marked, persistent improvement in all the patients throughout 4 years. The interval between injections could be extended in 46.1% of the patients (35% for adalimumab, 58% for etanercept) without provoking relapses. The mean therapy interval at the end of the study period was 3.12 weeks for adalimumab 40 mg (with respect to 2 weeks) and 2.75 weeks for etanercept 25 mg (with respect to 0.5 weeks). The new therapy timetable also led to cost savings. In conclusion, lengthening the time intervals between injections of anti-TNF agents in PsA patients who reach MDA is safe, effective, cost-effective, and facilitates patient compliance.

Neuroprotective effects of adalimumab on rats with experimental peripheral nerve injury: An electron microscopic and biochemical study.

Adalimumab, a new-generation anti-inflammatory agent, exerts its effect through tumor necrosis factor α (TNF-α), secreted from immune response cells such as macrophages and lymphocytes. TNF-α has been shown to play an important role in the processes of apoptosis and demyelination, and blockage of its activity may improve neural healing. Investigated in the present study is the probable neuroprotective influence of adalimumab in rats using a peripheral nerve injury model with biochemical and electron microscopic methods. Forty adult Wistar albino rats were randomly divided into control, sciatic nerve trauma, low-dose adalimumab, and high-dose adalimumab groups. Six rats from each group were assigned biochemical microscopy, and 4 were assigned electron microscopy. Neural injury was induced with clip compression following dissection of sciatic nerves. Adalimumab was simultaneously injected. The rats were sacrificed after 2 weeks of adalimumab treatment. Nerve tissue lipid peroxidation values were found to be significantly decreased in both the low- and high-dose adalimumab treatment groups, compared to the group subjected only to sciatic nerve trauma. Results demonstrate that adalimumab is an effective neuroprotective agent for neural healing, particularly in the early phase.

Crohn's disease outpatients treated with adalimumab have an earlier secondary loss of response and requirement for dose escalation compared to infliximab: A real life cohort study

BackgroundThe efficacy of anti-tumor necrosis factor alpha agents in maintaining remission in Crohn's disease may wane over time, leading to secondary loss of response that can often be overcome with dose escalation. Comparison of secondary loss of response of adalimumab and infliximab during long-term treatment of CD in a real-life IBD clinic has not been previously evaluated. MethodsA retrospective cohort study was conducted evaluating outpatients with CD on a maintenance regimen with adalimumab or infliximab from 200 to 2013 and who experienced a secondary loss of response. All infliximab-treated patients were anti-TNF naïve. Adalimumab-treated patients were stratified by prior anti-TNF exposure. Kaplan–Meier analysis was conducted to compare time to loss of response. Results218 CD patients met inclusion criteria (117 infliximab, 101 adalimumab). Median follow-up duration was 170.0weeks for infliximab and 122.0weeks for adalimumab (p=0.61). The proportion of patients with secondary loss of response was similar for infliximab-treated — 51.3% (60/117) compared to adalimumab patients naïve to anti-TNF therapy — 60.5% (23/38) (p=0.32), and adalimumab patients with prior anti-TNF exposure — 65.1% (41/63) (p=0.08). Median time to secondary loss of response was longer for infliximab patients (99.3wk, IQR 55.7–168.5) compared to both adalimumab patients naïve to anti-TNF therapy (58.9wk, IQR 29.0–85.7) (p=0.03), and adalimumab patients with prior anti-TNF exposure (52.7wk, IQR 20.1–85.0) (p<0.001). ConclusionsOver 50% of CD patients treated with infliximab and adalimumab develop secondary loss of response. Time to loss of response was shorter in patients treated with adalimumab compared to those treated with infliximab. Prior anti-TNF exposure further accelerated time to loss of response.

Su1397 Outpatients With Ulcerative Colitis Being Treated With Adalimumab and Infliximab Have Similar Rates of Loss of Response

Background: Biologic agents targeting tumour necrosis factor alpha (TNF-α), including infliximab and adalimumab, have been shown to be effective for induction and maintenance of remission in ulcerative colitis. However, during maintenance therapy response may be lost over time necessitating dose intensification, rescue corticosteroid therapy, or surgical intervention. A direct comparison of loss of response rates to adalimumab (ADA) and infliximab (IFX) during treatment of UC in a real-life IBD clinic has not been previously evaluated. Aims: The aim of this study was to compare, in UC patients treated with ADA or IFX, the proportion of patients who lost response during scheduled maintenance therapy, and to compare the time to loss of response for each agent. Methods: A retrospective cohort study evaluating anti-TNF Naive outpatients with UC entering into scheduled maintenance with ADA or IFX from 2004-2013 was conducted. All patients had completed the standard induction regimens for adalimumab and infliximab. Composite outcome for loss of response was defined by any one of: dose intensification (either increased dose or treatment frequency), surgical intervention, or rescue corticosteroid therapy. Kaplan-Meier analysis was used to assess maintenance of anti-TNF therapy over time. Logistic regression analysis was used to assess risk factors associated with loss of response. Results: 102 UC patients (60.8% male) met inclusion criteria. 36 patients (35.3%) were treated with adalimumab (ADA) and 66 patients (64.7%) were treated with infliximab (IFX). Disease distribution was pancolitic (73/ 102, 71.6%) or left-sided (29/102, 28.4%). Disease severity by mean partial Mayo score at anti-TNF induction was similar between the ADA (5.6±1.9) and IFX (6.2±2.3) groups. Mean follow-up duration was 139.0 weeks for ADA and 158.8 weeks for IFX. 21/36 (58.3%) ADA

Cost Per Clinical Remission and Clinical Response of Adalimumab, Golimumab, and Infliximab in the Treatment of Patients with Ulcerative Colitis: An Induction Analysis

Purpose: Adalimumab (ADA), golimumab (GLM), and infliximab (IFX) are anti-tumor necrosis factor (anti-TNF) therapies approved for treating ulcerative colitis (UC). No study has compared the cost effectiveness of all three of these therapies. This study compares the cost per clinical remission (CPR) and cost per clinical response (CPRes) for the induction period for ADA, GLM, and IFX in patients with UC who were anti-TNF naïve. Methods: Since the induction periods differed across the five randomized clinical trials that examined the efficacy of these treatments (8 weeks for ADA and IFX, 6 weeks for GLM), it was necessary to make assumptions as to how the placebo-adjusted efficacy rates would change over time. The five randomized clinical trials include two for ADA (ULTRA 1 and 2), one for GLM (PURSUIT), and two for IFX (ACT 1 and 2). In particular, we assumed that the efficacy for GLM would change via a linear function, concave function, or convex function between weeks 6 and 8. We performed a similar analysis, this time adjusting the IFX and ADA efficacy estimates from 8 weeks to 6 weeks to align with the GLM induction period. Treatment costs were calculated by applying the May, 2013 wholesale acquisition costs based on labeled dosing requirements. Infusion administration costs were included for IFX. Results: The CPR for GLM was $57,861, assuming that GLM would increase linearly, compared to $32,371 and $27,435 for IFX (ACT 1 and 2) and $94,193 and $85,048 for ADA (ULTRA 1 and 2). The CPR for GLM was $43,396 and $66,763, assuming concave and convex adjustment, respectively. The CPRes results were similar (Table 1). The results remained consistent for ADA and IFX when examining a 6-week, as opposed to an 8-week, induction period.Table 1: Results of cost per clinical remission and clinical response analysesConclusion: IFX and GLM had lower CPR and CPRes compared to ADA in the treatment of ulcerative colitis after adjusting for the different lengths of induction periods. Disclosure - Dr. Peter Mallow-Consultant: Janssen Scientific Affairs, LLC; Dr. John Rizzo-Consultant: Janssen Scientific Affairs, LLC; Dr. Mary Kay Queener-Employee: Janssen Scientific Affairs, LLC; Timothy Gathany-Employee: Janssen Research and Development; Dr. Jennifer Lofland-Employee: Janssen Scientific Affairs, LLC. This research was supported by an industry grant from Janssen Scientific Affairs, LLC.

THU0368 Dosage Reduction of Biological Therapy in Patients with Axial Spondyloarthritis in Persistent Clinical Remission.

BackgroundThe effectiveness of TNF blockers in treating axial Spondyloarthritis patients is well know, but we don’t know most appropriate dosage for treatment of patients in persistent clinical remission.ObjectivesOur objective is...

AB0500 A significant number of patients with rheumatoid arthritis receive low doses of biological agents in clinical practice

BackgroundThe dosages of biological agents used to treat rheumatoid arthritis (RA) have been established by randomized clinical trials. However, lower dosages of these agents may be prescribed in clinical practice...

FRI0163 Dosage reduction of biological drugs in patients with chronic arthritis: An observational study in clinical practice conditions

BackgroundBiological agents are used to treat chronic arthritis according to the standard doses from phase III clinical trials. However, in some patients, a good response to treatment may allow the...

Implementing treatment goals for successful long‐term management of psoriasis

Treatment goals are commonly used throughout medicine to ensure efficacious therapy of diseases and to prevent complications related to uncontrolled disease activity, such as the management of hypertension and diabetes. Psoriasis is a systemic immune-mediated inflammatory disease comprising characteristic skin manifestations. A range of co-morbidities has been associated with it, including diabetes and cardiovascular diseases such as myocardial infarction (MI) and stroke. There is good evidence that the severity of skin symptoms is related to mortality associated with MI. Therefore, long-term efficacious control of skin inflammation is the treatment paradigm of choice, particularly in patients with severe skin involvement. Surveys in a number of countries have revealed a substantial under-treatment of patients with moderate-to-severe psoriasis, leaving a considerable proportion without adequate disease control. In addition, a high number of patients were not satisfied with their treatment, including the time they needed to allocate for skin therapy and the number of visits to physicians. Therefore, the use of effective therapies is necessary to achieve appropriate control of inflammation and to improve patient satisfaction. The definition of treatment goals is an appropriate instrument for raising the quality of care and sets therapeutic standards in addition to evidence-based guidelines. Consensus treatment goals for moderate-to-severe psoriasis were recently defined, and a treatment goal algorithm was developed through a Delphi process by a group of experts from 19 European countries. These have since been adopted into the update of the German S3 guidelines for treatment of psoriasis. Furthermore, a novel analysis was carried out on published Phase 3 clinical trial data from three studies of adalimumab therapy in psoriasis, which used the consented definition of moderate-to-severe disease and the proposed treatment goal algorithm. The data showed that the 'treatment goal' was achieved in 68.2-79.3% of the patients treated with adalimumab by week 16, with >93% achieving 'treatment success' (a ≥75 reduction in psoriasis area and severity index compared with baseline). These results were similar to those achieved using the protocol-specified definitions of disease severity. Regular assessment of treatment goals during maintenance phase at intervals recommended by the published guidelines, such as 16 weeks for adalimumab, will ensure efficacious therapy over time. This may, consequently, represent progress towards establishing a standard of care for psoriasis.

The effectiveness and safety of adalimumab in the treatment of non‐reimbursed patients with mild‐to‐moderate psoriasis

Few reports exist on the use of biologics for treating patients with mild-to-moderate psoriasis, especially for non-reimbursed patients. This study aimed to evaluate the safety and effectiveness of adalimumab in non-reimbursed patients with mild-to-moderate psoriasis. Fifty one patients with mild-to-moderate psoriasis treated with adalimumab 40 mg every other week (eow) in a tertiary referral hospital in Taiwan between 2007 and 2010 were retrospectively reviewed. The clinical effectiveness of adalimumab was assessed using Subject's Global assessment (SGA) and Physician's Global Assessment (PGA), and the reasons for discontinuation were evaluated. After 12 weeks of adalimumab (40 mg subcutaneously eow without a loading dose) treatment, 66% and 74% of patients had SGA and PGA scores of at least marked improvement (greater than 50% improvement compared with baseline psoriasis), respectively, with 60% and 53% of patients achieving SGA and PGA scores of at least marked improvement after 24 weeks. Ten (71%) of 14 previous non-responders to etanercept achieved a SGA or PGA score of at least marked improvement after adalimumab treatment. Adalimumab was generally well tolerated, but four patients (7.8%) discontinued adalimumab due to adverse events. The mean time required for resumption of systemic anti-psoriatic therapy was 6 months (range, 1-12 months). Apart from financial limitations, the most common reasons for discontinuation were primary (23.5%) and secondary (13.7%) lack of efficacy. In non-reimbursed mild-to-moderate psoriasis patients, SGA and PGA remained high for adalimumab. Effectiveness and remission duration were key factors affecting patients' willingness to pay for prolonged adalimumab treatment.

Persistence with Anti-Tumor Necrosis Factor Therapies in Patients with Rheumatoid Arthritis: Observations from the RADIUS Registry

To evaluate persistence with anti-tumor necrosis factor (TNF) therapy and predictors of discontinuation in patients with rheumatoid arthritis (RA). This retrospective analysis used data from RADIUS 1, a 5-year observational registry of patients with RA, to determine time to first- and second-course discontinuation of etanercept, infliximab, and adalimumab. First-course therapy was defined as first exposure to anti-TNF therapy, and second-course therapy was defined as exposure to anti-TNF therapy after the first discontinuation. Kaplan-Meier survival analysis was used to assess persistence, log-rank tests were used to compare therapies, and Cox proportional hazards models were used to assess potential predictors of treatment discontinuation. This analysis included 2418 patients. Mean persistence rates were similar among treatments [first-course: etanercept, 51%; infliximab, 48%; adalimumab, 48% (followup was 54 weeks for etanercept and infliximab and 42 weeks for adalimumab); second-course: 56%, 50%, 46%, respectively (followup was 36 weeks for etanercept and infliximab and 30 weeks for adalimumab)]. Discontinuations of first-course therapy due to ineffectiveness were similar among treatments (etanercept, 19%; infliximab, 19%; adalimumab, 20%) and discontinuations due to adverse events were significantly (p = 0.0006) lower for etanercept than for infliximab (etanercept, 14%; infliximab, 22%; adalimumab, 17%). Predictors from univariable analysis of first- or second-course therapy discontinuation included increased comorbidities (etanercept), female sex (infliximab), Clinical Disease Activity Index > 22 (infliximab), and a Stanford Health Assessment Questionnaire score > 0.5 (adalimumab). In this population, first- and second-course persistence was similar among anti-TNF therapies. First-course discontinuation due to adverse events was lower with etanercept compared with infliximab.

Efficacy and safety of adalimumab in patients with plaque psoriasis who have shown an unsatisfactory response to etanercept

The safety and efficacy of adalimumab in patients who have shown an unsatisfactory response to etanercept are unknown. We sought to evaluate the safety and efficacy of adalimumab in patients who failed to show a satisfactory response or lost their satisfactory response to etanercept. This multicenter study enrolled patients who either failed to reach a physician global assessment (PGA) score of 0 or 1 after 12 weeks of etanercept (group A; 50 patients) or who lost their PGA score of 0 or 1 at any time after etanercept dose decrease from 50 mg twice a week to 50 mg every week (group B; 35 patients). Patients received adalimumab 40 mg every other week without loading dose for 12 weeks followed by 40 mg every week for an additional 12 weeks if they did not reach a PGA score of 0 or 1. After 12 weeks of adalimumab, 34.0% (n = 17; 95% confidence interval [CI] 20.4-47.6) and 31.4% (n = 11; 95% CI 15.2-47.6) of patients from groups A and B, respectively, reached a PGA score of 0 or 1. A total of 46.0% (n = 23; 95% CI 31.7-60.3) and 45.7% (n = 16; 95% CI 28.4-63.1) of patients from group A and B, respectively, achieved a PGA score of 0 or 1 after 24 weeks of adalimumab. Adalimumab was well tolerated and no serious adverse events were reported. This was an open-label uncontrolled study. Adalimumab should be considered as an alternative in patients with psoriasis who have not shown an adequate response or who lost their response to etanercept after a dose decrease.

British Association of Dermatologists’ guidelines for biologic interventions for psoriasis 2009

St John’s Institute of Dermatology, King’s College London and Guy’s and St Thomas’ NHS Foundation Trust, London SE1 9RT U.K. *Department of Dermatology, Royal Gwent Hospital, Newport NP20 2UB, U.K. Department of Dermatology, Western Infirmary, Glasgow G11 6NT, U.K. The Dermatology Centre, Salford Royal Hospital, University of Manchester, Manchester Academic Health Science Centre, Manchester M6 8HD, U.K. §Psoriasis and Psoriatic Arthritis Alliance, PO Box 111, St Albans AL2 3JQ, U.K. –Department of Dermatology, Cardiff University, School of Medicine, Heath Park, Cardiff CF14 4XN, U.K. **Royal National Hospital for Rheumatic Diseases, Bath BA1 1RL, U.K. Department of Dermatology, Belfast City Hospital, Belfast BT9 7AB, U.K. Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE2 4HH, U.K. §§Department of Dermatology, Aberdeen Royal Infirmary, Foresterhill, Aberdeen AB9 2ZB, U.K.

Effect of adalimumab on joint disease: features of patients with psoriatic arthritis detected by magnetic resonance imaging

Background:Bone marrow oedema (BMO), synovitis, effusion and joint erosion on magnetic resonance imaging (MRI) may be used as outcome measures in psoriatic arthritis (PsA).Objective:To assess the impact of adalimumab on...