Trial Of Adalimumab Research Articles

Sa1132 A Retrospective Cohort Study of Rates of Clostridium difficile Infection in Moderate-to-Severe Inflammatory Bowel Disease Patients Treated With Vedolizumab vs. Infliximab at a Canadian Tertiary Hospital

Background: This study evaluated the long-term safety of adalimumab (ADA), as used in routine clinical practice, for up to 6 years in patients with moderately to severely active Crohn's disease (CD) enrolled in the global observational registry PYRAMID. Methods: All patients entering the multi-centre, non-interventional registry PYRAMID were to be followed for up to 6 years. Adverse events (AEs) were collected from the first dose to up to 70 days after the last dose of ADA or through the cutoff of 1 December 2013. AE rates are reported as per 100 patient-years (PY). Results: A total of 5061 patients (57.1% female, mean age 37.8 years, median duration of CD 8.2 years) have enrolled in PYRAMID, totaling 13924.3 PY of ADA exposure, excluding prior exposure in CD ADA clinical trials. As of 01 Dec 2013, 2885 patients (57%) were still participating and 297 patients (5.9%) had at least 6 years of ADA exposure. A total of 2600 patients (51%) received biologic therapy prior to enrollment (98.3% infliximab, 5.6% certolizumab, 1.4% natalizumab, 0.5% other). During the study, concomitant corticosteroids (CS), immunosuppressants (IMM), and IMM + CS were used by 29.4%, 35.6%, and 11.6% of patients, respectively. A total of 682 patients (4.9/100 PY) experienced serious infections, of which 265 patients (5.1/100 PY) were on combination therapy with IMM and 417 patients (4.8/100 PY) were on ADA monotherapy. A total of 104 patients (0.7/100 PY) experienced any malignancy, of which 50% had received combination therapy with IMM. Thirty-eight treatment-emergent deaths (0.3/100 PY) were reported, of which 7 were considered possibly related to ADA. Overall, ADA-exposed patients did not have an increased mortality versus the general population. The Table shows an overview of exposure-adjusted registry treatment-emergent AEs for years 3, 5, and 6. Conclusion: After up to 6 years of observation, long-term ADA exposure continued to be welltolerated in patients with moderately to severely active CD. No new safety signals were identified. AE rates remained stable over time. Table. Cumulative incidence of treatment-emergent adverse events (AEs) excluding prior exposure in other CD ADA trials

SAT0339 Asas40 and ASDAS Responses Are Associated with Improved Physical Function, Hrqol, and Work Productivity in Patients with Non-Radiographic Axial Spondyloarthritis

BackgroundASAS40 response has been used as a primary endpoint in clinical trials of patients (pts) with axial spondyloarthritis (axSpA), and ASDAS inactive disease is recommended as a treatment target. However,...

FRI0138 A Psychometric Analysis of Outcome Measures in Trials of Peripheral Spondyloarthritis

BackgroundIn peripheral spondyloarthritis (pSpA), no specific efficacy endpoint has been developed representing improvement in arthritis, enthesitis, and/or dactylitis.ObjectivesTo assess the discriminatory aspects of disease activity measures and response criteria between...

Spinal Inflammation in the Absence of Sacroiliac Joint Inflammation on Magnetic Resonance Imaging in Patients With Active Nonradiographic Axial Spondyloarthritis

ObjectiveTo evaluate the presence of spinal inflammation with and without sacroiliac (SI) joint inflammation on magnetic resonance imaging (MRI) in patients with active nonradiographic axial spondyloarthritis (SpA), and to compare the disease characteristics of these subgroups.MethodsABILITY-1 is a multicenter, randomized, controlled trial of adalimumab versus placebo in patients with nonradiographic axial SpA classified using the Assessment of SpondyloArthritis international Society axial SpA criteria. Baseline MRIs were centrally scored independently by 2 readers using the Spondyloarthritis Research Consortium of Canada (SPARCC) method for the SI joints and the SPARCC 6–discovertebral unit method for the spine. Positive evidence of inflammation on MRI was defined as a SPARCC score of ≥2 for either the SI joints or the spine.ResultsAmong patients with baseline SPARCC scores, 40% had an SI joint score of ≥2 and 52% had a spine score of ≥2. Forty-nine percent of patients with baseline SI joint scores of <2, and 58% of those with baseline SI joint scores of ≥2, had a spine score of ≥2. Comparison of baseline disease characteristics by baseline SI joint and spine scores showed that a greater proportion of patients in the subgroup with a baseline SPARCC score of ≥2 for both SI joints and spine were male, and patients with spine and SI joint scores of <2 were younger and had shorter symptom duration. SPARCC spine scores correlated with baseline symptom duration, and SI joint scores correlated negatively with the baseline Bath Ankylosing Spondylitis Disease Activity Index, but neither correlated with the baseline Ankylosing Spondylitis Disease Activity Score, total back pain, the patient's global assessment of disease activity, the Bath Ankylosing Spondylitis Functional Index, morning stiffness, nocturnal pain, or C-reactive protein level.ConclusionAssessment by experienced readers showed that spinal inflammation on MRI might be observed in half of patients with nonradiographic axial SpA without SI joint inflammation.

Recovery of clinical but not radiographic outcomes by the delayed addition of adalimumab to methotrexate-treated Japanese patients with early rheumatoid arthritis: 52-week results of the HOPEFUL-1 trial

Objective. The aim of this study was to compare efficacy outcomes of initial treatment with adalimumab + MTX vs adalimumab addition following 26 weeks of MTX monotherapy in Japanese early RA patients naive to MTX with high disease activity.Methods. Patients completing the 26-week, randomized, placebo-controlled trial of adalimumab + MTX were eligible to receive 26 weeks of open-label adalimumab + MTX. Patients were assessed for mean change from baseline in the 28-joint DAS with ESR (DAS28-ESR) and modified total Sharp score (mTSS), and for the proportions of patients achieving clinical, functional or radiographic remission.Results. Of 333 patients assessed, 278 (137 from the initial adalimumab + MTX and 141 from the initial placebo + MTX groups) completed the 52-week study. Significant differences in clinical and functional parameters observed during the 26-week blinded period were not apparent following the addition of open-label adalimumab to MTX. Open-label adalimumab + MTX slowed radiographic progression through week 52 in both groups, but patients who received adalimumab + MTX throughout the study exhibited less radiographic progression than those who received placebo + MTX during the first 26 weeks (mean ΔmTSS at week 52 = 2.56 vs 3.30, P < 0.001).Conclusion. Delayed addition of adalimumab in Japanese MTX-naive early RA patients did not impact clinical and functional outcomes at week 52 compared with the earlier addition of adalimumab. However, the accrual of significant structural damage during blinded placebo + MTX therapy contributed to the persistence of differences between the treatment strategies, suggesting that Japanese patients at risk for aggressive disease should benefit from the early inclusion of adalimumab + MTX combination therapy.Trial registration. ClinicalTrials.gov (http://clinicaltrials.gov/), NCT00870467.

Anti-TNF agents as therapeutic choice in immune-mediated inflammatory diseases: focus on adalimumab.

The complex pathogenesis of immune-mediated inflammatory diseases (IMIDs) has been extensively investigated and dysregulation of cytokines, such as tumour necrosis factor (TNF) has been shown to play a dominant role in the pathogenesis of various IMIDs, such as rheumatoid arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, psoriasis and psoriatic arthritis. The subsequent development of biological agents capable of blocking TNF has led to important advances in the pharmacotherapy of such diseases and confirmed the concept of a common pathophysiology among IMIDs with TNF having a predominant role. Five TNF inhibitors have currently been approved for treatment of one or more IMIDs; these include infliximab, etanercept, adalimumab, golimumab and certolizumab pegol. Given the similarities in the pathogenic background of IMIDs, one could expect that anti-TNF agents be similarly effective and with comparable tolerability profiles; however, this may not be the case. Structural and pharmacological differences among the anti-TNF drugs are likely to result in differences in efficacy and tolerability among the agents in the different IMIDs, together with differences in potency, therapeutic dose ranges, dosing regimens, administration routes, and propensity for immunogenicity. Among the five TNF inhibitors approved for treatment of IMIDs, adalimumab has the widest range of indications. Data from controlled clinical trials of adalimumab, showing its excellent efficacy and tolerability in a wide range of indications, are supported by real-world long-term data from observational studies, which confirm the value of adalimumab as a suitable choice in the management of IMIDs.

Increased Risk of Malignancy With Adalimumab Combination Therapy, Compared With Monotherapy, for Crohn's Disease

Few studies have assessed the risk of malignancy from anti-tumor necrosis factor monotherapy or combination therapy for Crohn's disease (CD). We determined the relative risk of malignancy in patients with CD who received adalimumab monotherapy, compared with the general population. We also compared the risk of malignancy associated with combination adalimumab and immunomodulator therapy with that of adalimumab monotherapy. We performed a pooled analysis of data from 1594 patients with CD who participated in clinical trials of adalimumab (CLASSIC I and II, CHARM, GAIN, EXTEND, and ADHERE studies; 3050 patient-years of exposure). We calculated rates of malignancy among patients; the expected rates of malignancy, based on the general population, were derived from the Surveillance, Epidemiology, and End Results registry and National Cancer Institute survey. Compared with the general population, patients receiving adalimumab monotherapy did not have a greater than expected incidence of nonmelanoma skin cancer (NMSC) or other cancers, whereas those receiving combination therapy had a greater than expected incidence of malignancies other than NMSC (standardized incidence ratio, 3.04; 95% confidence interval [CI], 1.66-5.10) and of NMSC (standardized incidence ratio, 4.59; 95% CI, 2.51-7.70). Compared with patients receiving adalimumab monotherapy, those patients receiving combination therapy had an increased risk of malignancy other than NMSC (relative risk, 2.82; 95% CI, 1.07-7.44) and of NMSC (relative risk, 3.46; 95% CI, 1.08-11.06). In patients with CD, the incidence of malignancy with adalimumab monotherapy was not greater than that of the general population. Co-administration of immunomodulator therapy and adalimumab was associated with an increased risk of NMSC and other cancers.

Treating to a Target in Established Active Rheumatoid Arthritis Patients Receiving a Tumor Necrosis Factor Inhibitor: Results From a Real‐World Cluster‐Randomized Adalimumab Trial

In early rheumatoid arthritis (RA), treating to a target is more effective than routine care (RC). Our aim was to determine if treating to a target has better outcomes than RC in established active RA. We used a real-world, 18-month cluster-randomized trial in established active RA patients treated with adalimumab. Physicians were randomized to RC, treating to a Disease Activity Score in 28 joints (DAS28) of <2.6 (DAS group), or treating to a 0 of 28 swollen joint count (SJC; 0-SJC group). Among the 308 enrolled patients, 109 (35.4%) were randomized to RC, 100 (32.5%) to the DAS group, and 99 (32.1%) to the 0-SJC group. When adjusting for baseline DAS28, a comparable but significant (P < 0.001) improvement in DAS28 was observed at 12 months for all groups (DAS28 mean score 3.1, 3.4, and 3.2, respectively). There were no significant between-group differences in the improvement of clinical parameters and patient-reported outcomes with the exception of the mean change in patient satisfaction over time (P = 0.020), which was highest in the DAS group. Time to achieving good/moderate European League Against Rheumatism (EULAR) response was significantly shorter in the targeted treatment groups compared to RC (adjusted hazard ratio [HR] for the DAS-group 2.99 [95% confidence interval (95% CI) 1.71-5.24] and HR for the 0-SJC group 1.86 [95% CI 1.09-3.13]). The dropout rate was 52.3% in RC, 27% in the DAS group, and 22.2% in the 0-SJC group (P < 0.001). All groups experienced significant improvements at 18 months of treatment with adalimumab. Treating to target in established RA did not differ from RC in terms of therapeutic end point achievement for patients remaining on treatment. However, time to achieving good/moderate EULAR response was significantly shorter in the targeted treatment groups compared to RC and, importantly, the dropout rate was significantly lower with targeted treatment.

A Randomized, Double-Blind, Placebo Controlled Trial of Adalimumab for Interstitial Cystitis/Bladder Pain Syndrome

The efficacy of adalimumab for the treatment of interstitial cystitis/bladder pain syndrome was investigated in a phase III, randomized, double-blind, placebo controlled, proof of concept study. Patients with interstitial cystitis/bladder pain syndrome were randomized to receive a loading dose of 80 mg subcutaneous adalimumab followed by 40 mg every 2 weeks or subcutaneous placebo for 12 weeks, and outcome measures were assessed. The incidence of adverse events was also assessed. Of a total of 43 patients 21 received adalimumab and 22 received placebo. Of the patients who received adalimumab, there was a statistically significant improvement demonstrated in the O'Leary-Sant Interstitial Cystitis Symptom and Problem Indexes (p = 0.0002), Interstitial Cystitis Symptom Index (p = 0.0011), Interstitial Cystitis Problem Index (p = 0.0002), and Pelvic Pain, Urgency, Frequency Symptom Scale (p = 0.0017) at 12 weeks compared to baseline. At 12 weeks 11 of 21 (53%) patients in the adalimumab group had a 50% or greater improvement in global response assessment (p ≤ 0.0001). There was not a statistically significant improvement in any outcome measure in patients receiving adalimumab compared to placebo. There were no significant adverse events. Adalimumab treatment resulted in a statistically significant improvement in outcome measures compared to baseline in patients with moderate to severe interstitial cystitis/bladder pain syndrome. Adalimumab failed to demonstrate positive proof of concept compared to placebo due to a significant placebo effect.

AB0279 Incidence of diabetes and effect of etanercept and adalimumab on hba1c over 1 year: data from a randomised trial in patients with rheumatoid arthritis

BackgroundInflammation such as that which occurs in rheumatoid arthritis (RA) is associated with insulin resistance and risk of diabetes mellitus (DM). Some DMARDs including TNF inhibitors (TNFi) may improve insulin...

SAT0052 Structural Damage by Radiography Predicts Cardiovascular Risk in Patients with Rheumatoid Arthritis

BackgroundPatients (pts) with rheumatoid arthritis (RA) are at-risk for cardiovascular (CV) disease, even when accounting for traditional risk factors (eg, hypertension, dyslipidemia). This increased risk is usually attributed to high...

FRI0270 Concurrent sacroiliac joint and spinal inflammation on MRI in patients with non-radiographic axial spondyloarthritis

BackgroundThe imaging arm of the ASAS axial spondyloarthritis (SpA) criteria requires the presence of sacroiliitis on MRI or radiographs. In patients (pts) with non-radiographic axial SpA (nr-axSpA), there may be...

AB0459 Analysis of integrated radiographic data for two long-term, open-label extension studies of adalimumab

BackgroundAccurate analysis of radiographic progression in rheumatoid arthritis (RA) has been challenging because most evaluations use change in Sharp score either between only 2 time points or between multiple time...

FRI0286 Burden of the disease in axial spondyloarthritis

BackgroundAxial spondyloarthritis (axSpA) is a new classification that includes ankylosing spondylitis (AS) and nonradiographic axSpA (nr-axSpA). Little is known about the severity and progressive nature of nr-axSpA relative to AS....

FRI0425 Similar levels of disease activity in patients with oligoarticular vs. polyarticular peripheral spondyloarthritis

BackgroundThe ASAS criteria for peripheral spondyloarthritis (SpA) allow for classification of patients with SpA who present with peripheral arthritis, enthesitis and/or dactylitis.1 ABILITY-2, a placebo-controlled trial of adalimumab (ADA) for...

FRI0414 Tocilizumab in methotrexate-intolerant or contraindicated patients – a cost-utility model for scotland

BackgroundTocilizumab (TCZ) is indicated for the treatment of adult rheumatoid arthritis (RA) that has responded inadequately to one or more disease-modifying antirheumatic drugs (“DMARD-IR patients”). Whilst typically given with methotrexate...

OP0105 Effect of Adalimumab on Physical Function, Health-Related Quality of Life, and Work Productivity in Patients with Peripheral Spondyloarthritis: Results from the Ability-2 Clinical Trial

BackgroundSpondyloarthritis is associated with impaired physical function, health-related quality of life (HRQL), and work productivity. Adalimumab (ADA) is associated with improved clinical outcomes in patients with peripheral spondyloarthritis (pSpA).ObjectivesTo evaluate...

THU0275 Sustained efficacy of adalimumab in patients with non-radiographic axial spondyloarthritis: Week 68 results from ability 1

BackgroundABILITY 1 demonstrated that adalimumab (ADA) is effective in reducing the signs and symptoms of non-radiographic axial spondyloarthritis (nr-axSpA) compared to placebo (PBO) at Week (Wk) 12.1ObjectivesTo describe the long-term...

AB0188 Combination therapy with adalimumab plus methotrexate reduces circulating levels of pro-matrix matalloproteinases-1 and -3 independently of clinical disease activity in patients with rheumatoid arthritis

BackgroundIn patients (pts) with rheumatoid arthritis (RA), therapy with biologic agents such as adalimumab (ADA) can uncouple destruction of articular cartilage and bone from the inflammatory processes that drive clinical...

PSY9 - A network meta-analysis of randomized, controlled trials of ustekinumab and adalimumab for moderate-to-severe psoriasis

PSY9 - A network meta-analysis of randomized, controlled trials of ustekinumab and adalimumab for moderate-to-severe psoriasis