Clinical Trials Of Adalimumab Research Articles

Possibilities and Limitations in Substituting anti-Drug Antibody Titers with Signal-to-Noise Ratios: A Comprehensive Comparison Using Two Clinical Trial Datasets of Adalimumab.

Immunogenicity assessment is vital in clinical trials and is measured through a multi-tiered approach (screening, confirmatory and titer assays). However, recent studies have suggested that titer results could be reported from ADA signal-to-noise ratios (S/N ratios=sample mean signal/negative control mean signal). More data analysis using two clinical trials of adalimumab: SB5-1003 (single-dose, healthy participants) and SB5-4001 (multiple-dose, interchangeability study, patients with plaque psoriasis), therefore, is indispensable whether substituting ADA S/N ratio as an alternative way of reporting titer results has no impact on interpretation on clinical outcome. In this study, we demonstrated that there is a strong correlation between S/N ratios and titers and no impact on overall PK results. Nonetheless, sub-analyses with time or adalimumab level showed a change in the regression between S/N ratios and titers, leading to different titer values from the same S/N ratio. These data demonstrate that S/N ratios may fully replace titers in limited circumstances such as a biosimilar study which goal is to prove equivalence between the originator and candidate product, but need a caution in other cases.

Refining how we measure as we test: new insights using adalimumab in patients with hidradenitis suppurativa.

In the SOLACE study, Gulliver et al.1 evaluate the real-world effectiveness of adalimumab, the first, and, to date, only medication approved for treatment of hidradenitis suppurativa (HS), a debilitating condition characterized by recurrent inflammatory nodules, abscesses, and fistulas. In this large open-label cohort of 138 patients treated with adalimumab, 68.9% achieved HiSCR (a 50% reduction in inflammatory lesion counts) at week 24, higher than the results seen in the PIONEER studies at week 12. Patients with medium to high inflammatory lesion counts (abscesses and inflammatory nodules AN) counts experienced the best response. During the pivotal adalimumab clinical trials, primary endpoints were based on the HiSCR,2 a measure that was analytically derived from the convergence of clinical and patient-reported data in an adalimumab trial. HiSCR does not incorporate improvements in fistulae. Since then, additional tools have emerged including the International HS Severity Score System (IHS4)3 which designates higher weights to draining fistulas and abscesses and, therefore, measures something different than HiSCR. As there is an overlap in the measures, it is not surprising that Gulliver et al. demonstrated that HiSCR responders also had a decrease in IHS4 scores. The best IHS4 responders were those with high AN counts, which seem most responsive to adalimumab. This finding is consistent with work by Frew et al.,4 who did not demonstrate a significant change in the IHS4 category when retrospectively applying the IHS4 to the PIONEER 1 data. Fistulas are an extremely important part of HS, and better treatment options as well as ways to measurement the impact of improvement may still emerge. In the meantime, it seems reasonable to use both scores. It is hard to get HS under control. The first studies with adalimumab showed successful treatment required relatively high doses. Taking into account the open-label design and some population differences, this study confirms that a long duration of treatment may be important to achieve desired clinical effect: the proportion of patients who achieved HiSCR increased from 69% at week 24 to 82% and 75% at week 52 for patients.2 It is difficult to maintain placebo groups past a few months in placebo controlled studies. Given the advances in the field, now is the time to move into an era with more head-to-head comparisons, which will also allow the use of longer primary endpoints. In the meantime, the guidance that it takes time to attain desired effects with adalimumab and other treatments is important for patients and physicians. HS is still hard to treat, but we are continuing to improve both our approach and our results. Dr. Kimball is a consultant and investigator for Abbvie, Bristol Meyers Squibb, Janssen, Eli Lilly, Novartis, Pfizer, and UCB, Incyte; consultant for Regeneron and Bayer, receives fellowship funding from Janssen and Abbvie; and is on the Board of Directors of Almirall. None.

Low Incidence of Inflammatory Bowel Disease Adverse Events in Adalimumab Clinical Trials Across Nine Different Diseases.

ObjectiveAdalimumab is approved for treatment of Crohn’s disease and ulcerative colitis. Thus, we postulated that exacerbation or new‐onset of inflammatory bowel disease (IBD) would be rare events in patients treated with adalimumab for non‐IBD indications. The objective was to evaluate the incidence of IBD adverse events (AEs) across adalimumab trials.MethodsIBD AE rates in 75 adalimumab clinical trials in rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, pediatric enthesitis‐related arthritis, uveitis, hidradenitis suppurativa, adult and pediatric psoriasis, psoriatic arthritis, nonpsoriatic arthritis peripheral spondyloarthritis (SpA), axial SpA, including nonradiographic axial SpA, and ankylosing spondylitis, were analyzed. Search terms for IBD AEs (new onset or worsening/flare) included IBD, ulcerative colitis, Crohn’s disease, and ulcerative proctitis.ResultsThis analysis included 24,114 patients, representing 36,508 patient‐years of adalimumab exposure. The overall rate of IBD AEs in adalimumab‐treated patients was 0.1 (95% confidence interval [95% CI] 0.1–0.2)/100 patient‐years (41 events), ranging from no events (psoriatic arthritis, uveitis, and pediatric trials) to 0.8 (95% CI 0.2–2.2)/100 patient‐years in peripheral SpA. The rate of IBD in axial SpA was 0.6 (95% CI 0.4–1.0)/100 patient‐years. During placebo‐controlled trials, the overall IBD rate was 0.1 (95% CI 0.0–0.3)/100 patient‐years for adalimumab groups (3 events in 6,781 patients; 2,752 patient‐years of exposure) and 0.1 (95% CI 0.0–0.4)/100 patient‐years for placebo groups (1 event in 3,493 patients; 1,246 patient‐years of exposure). IBD rates in axial SpA were 0.5 (95% CI 0.1–1.4)/100 patient‐years for adalimumab and 0.6 (95% CI 0.0–3.1)/100 patient‐years for placebo.ConclusionThe rates of IBD AEs in adalimumab clinical trials were generally low across the evaluated diseases, including axial SpA; all events occurred in adult patients.

Long-term safety of adalimumab in clinical trials in adult patients with Crohn's disease or ulcerative colitis.

Adalimumab is used to treat moderate to severe Crohn's disease (CD) and ulcerative colitis (UC) when conventional therapies fail. To update long-term adalimumab safety from CD and UC trials; the previous report was CD only, 3160 patients/3402 patient-years (PYs). Treatment-emergent adverse events (AEs; first dose to 70days after last dose/December 31, 2015) in adults in phase 2/3 and 3/3b trials and open-label extensions were coded using Medical Dictionary for Regulatory Activities (MedDRA-v18.1). Rates were assessed as events/100 (E/100 PYs). The database (16 trials; CD, N=3606; UC, N=1739) represented 4145 and 3397 PYs of exposure, respectively. For CD, incidences of any AEs with adalimumab were 60.8%-65.1%, depending on dose, and 71.5% with placebo; for UC, the incidences were 53.5%-54.8% and 56.1%, respectively. Rates of any AEs (CD, 605 E/100 PYs; UC, 361 E/100 PYs), serious AEs (CD, 36.1 E/100 PYs; UC, 18.9 E/100 PYs), and malignancies (CD, 1.2 E/100 PYs; UC, 1.0 E/100 PYs) were similar between current and prior analyses. Apparent rate of opportunistic infections was lowered to 0.3 and 0.2 E/100 PYs for CD and UC, respectively, by recent MedDRA changes excluding oral candidiasis and tuberculosis. Standardised incidence ratios for malignancies were similar to the general population (CD, 1.45 [95% CI, 0.90-2.22]; UC, 1.36 [95% CI, 0.84-2.07]). Demyelinating disorders were uncommon (CD, 0.1 E/100 PYs; UC, <0.1 E/100 PYs). Patients with moderately to severely active Crohn's disease or ulcerative colitis continued to experience acceptable safety with adalimumab, without new safety signals.

Incidence of Inflammatory Bowel Disease Events in Adalimumab Clinical Trials Across Indications

Abstract Not Available Disclosures: Study supported by AbbVie.

Crohn's Disease Activity and Concomitant Immunosuppressants Affect the Risk of Serious and Opportunistic Infections in Patients Treated With Adalimumab.

Anti-tumor necrosis factor (TNF) drugs are commonly used to treat moderate-to-severe Crohn's disease (CD). Both the activity of CD and the concomitant immunosuppressants (corticosteroids and immunomodulators) used with anti-TNF drugs could increase the risk of infection. We determined the relative risk of serious and opportunistic infections associated with increasing disease activity and concomitant immunomodulators and corticosteroids in patients with CD treated with adalimumab. This pooled analysis identified incident treatment-emergent serious and opportunistic infections among patients with CD in clinical trials of adalimumab. Disease activity was assessed with the Crohn's Disease Activity Index (CDAI). The analysis included 2,266 patients treated with adalimumab with median age 35 years. Higher disease activity was associated with significantly increased risks of both serious and opportunistic infections at 1 year, with each 100-point increase in CDAI associated with a >30% increased risk of each type of infection. Concomitant use of immunomodulators was associated with a significant >3-fold decreased risk of serious infection (hazard ratio (HR) 0.29 (0.08-0.98), P=0.045) by 1 year. Concomitant use of corticosteroids was associated with a significantly increased risk of serious infection by day 120 (HR 2.40 (1.33-4.35), P=0.004). Concomitant use of either category of immmunosuppressant was associated with numerically higher rates of opportunistic infection, 40% of which were due to herpes zoster, compared with adalimumab monotherapy. Higher disease activity in CD is associated with significantly increased risks of both serious and opportunistic infections. In addition to corticosteroid-sparing strategies, consideration should be given to expanding herpes zoster vaccination guidelines to include younger patients.

Adalimumab long-term safety: infections, vaccination response and pregnancy outcomes in patients with rheumatoid arthritis

BackgroundAdalimumab has been used in patients with moderately to severely active rheumatoid arthritis (RA) for over 10 years and has a well-established safety profile across multiple indications.ObjectiveTo update adverse events...

Long-term safety of adalimumab in clinical trials for adult patients with moderate to severe plaque psoriasis

Long-term safety of adalimumab in clinical trials for adult patients with moderate to severe plaque psoriasis

Long-Term Safety of Adalimumab in Clinical Trials in Adult Patients With Crohnʼs Disease or Ulcerative Colitis

Introduction: Adalimumab (ADA) is a fully human anti-tumor necrosis factor (TNF) monoclonal antibody used for the treatment of moderate to severe Crohn's disease (CD) and ulcerative colitis (UC) in patients who have inadequately responded to conventional therapies. Safety from ongoing ADA trials continues to be collected, allowing assessment of long-term safety as the number of patients and the amount of exposure to ADA increase. The aim is to provide an update on the long-term safety profile of ADA in CD and UC patients. Methods: Safety data were evaluated for adult patients with CD or UC treated with ADA in randomized, placebo-controlled, phase 3 and 3b trials as well as their open-label extension studies. Treatmentemergent adverse events (AEs) were coded using the Medical Dictionary for Regulatory Activities, version 17.1(2014), and collected from the first dose to up to 70 days after the last dose or through the cutoff date of 31 Dec 2014. AE rates were assessed as events (E) per 100 patient-years (PYs) of exposure to ADA. Results: As of 31 Dec 2014, the ADA clinical safety database contained data for 3689 CD patients and 1789 UC patients, representing 4178.7 and 3371.9 PYs of ADA exposure, respectively. Overall, AE, SAE, and malignancy rates per PYs exposure were similar between the prior and the most recent data cutoffs for each disease state (Table). The type of infections in the Opportunistic infections (excluding TB) category changed in 2014 resulting in an apparent decreased rate (Table). Conclusion: ADA continues to be well tolerated in patients with moderately to severely active CD and UC. No new safety signals were identified with prolonged ADA use in these patient groups.Table 1: Safety Profile of Adalimumab in Adult CD and UC Patients

Sa1131 PYRAMID Registry: An Observational Study of Adalimumab in Crohn's Disease: Results at Year 6

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

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

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.

Pyramid Registry: An Observational Study of Adalimumab in Crohnʼs Disease: Results at Year Five

Purpose: To evaluate the long-term safety of adalimumab (ADA), up to 5 years (yrs), as it is used in routine clinical practice in patients (pts) with moderately to severely active Crohn's disease (CD) from the observational registry PYRAMID. Methods: All pts entering the multicenter, non-interventional registry PYRAMID were to be followed for up to 6 yrs. Adverse events (AEs) were collected from the first dose up to 70 days after the last dose of ADA or through the December 1, 2012 cut-off. Rates of AEs were assessed per 100 patient-yrs (PY). Results: A total of 5,061 pts (57% female, mean age 37.8 yrs, median duration of CD 8.2 yrs) have enrolled in PYRAMID, totaling 13,914.2 PY of exposure, including prior exposure in CD ADA clinical trials. As of Dec 1, 2012, 3197 pts (63.2%) were still participating, and 397 pts (7.8%) had up to 5 yrs of ADA exposure. Of the 2,600 pts (51%) who received biologic therapy prior to enrollment, 98% were infliximab-experienced. Concomitant corticosteroids (CS), immunosuppressants (IMM), and IMM + CS were used by 30%, 36%, and 12% of pts, respectively. More pts receiving ADA combination therapy with IMM and/or CS-experienced serious infections than pts receiving ADA monotherapy (10.7%/10.2% vs 7.3%, p<0.02). Standardized mortality ratios, calculated using the most recent country-specific mortality rates in a general population through 2006, were 0.90 (95% confidence interval [CI] 0.64-1.24) overall; 1.10 (95% CI 0.65-1.74) for females, and 0.77 (95% CI 0.46-1.20) for males. There were 37 treatment-emergent deaths reported; six of the 37 were considered possibly related to ADA. The table shows an overview of exposure-adjusted registry treatment-emergent AEs for years 3 and 5. Conclusion: At the 5-year timepoint, long-term ADA exposure continues to be well-tolerated in pts with moderately to severely active CD. No new safety signals have been identified. AE rates have remained stable over time. Disclosure - D'Haens: Consultant: AbbVie, Actogenix, Boehringer Ingelheim, Janssen, Cosmo Technologies, Elan, Engene, Ferring Pharmaceuticals, Giuliani, GlaxoSmithKline, Merck, MSD, Neovacs, Novonordisk, Otsuka, PDL Biopharma, Pfizer, SetPoint, Shire, Takeda, Teva, UCB; Speakers fees: AbbVie, Tillotts, Tramedico, Ferring, MSD, UCB, Norgine, Shire; Financial support for research: AbbVie, Jansen Biologics, Given Imaging, MSD, DrFalk Pharma, Photopill Reinisch: has served as a speaker, a consultant and/or an advisory board member for AbbVie, Aesca, Amgen, Astellas, Astra Zeneca, Biogen IDEC, Bristol-Myers Squibb, Cellerix, Chemocentryx, Celgene, Janssen, Danone Austria, Elan, Ferring, Genentech, Grünenthal, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid Therapeutics, Millenium, Mitsubishi Tanabe Pharma Corporation, MSD, Novartis, Ocera, Otsuka, PDL, Pharmacosmos, Pfizer, Procter & Gamble, Prometheus, Robarts Clinical Trial, Schering-Plough, Setpointmedical, Shire, Takeda, Therakos, Tigenix, UCB, Vifor, Yakult, Zyngenia, Austria and 4SC. Satsangi: none declared Loftus: Consultant: AbbVie, UCB, Janssen Biotech, Elan, Hospira, Eisai, Given; Financial support for research: AbbVie, UCB, Janssen Biotech, Millenium (now Takeda), GlaxoSmithKline, Amgen, Pfizer, Santarus, Braintree, Genentech, Bristol-Myers Squibb, Shire Panaccione: has received consultant and/or lecture fees from AbbVie, Amgen, AstraZeneca, Axcan Pharma (now Aptalis), Biogen Idec, Bristol-Myers Squibb, Centocor, ChemoCentryx, Eisai Medical Research Inc, Elan Pharmaceuticals, Ferring, Genentch, GlaxoSmithKline, Janssen, Merck Sharp and Dohme Corp, Millenium Pharmaceuticals Inc (now Takeda), Ocera Therapeutics Inc, Otsuka America Pharmaceutical, Pfizer, Shire Pharmaceuticals, Prometheus Labs, Schering-Plough, Synta Pharmaceuticals Corp, Teva, UCB Pharma, and Warner Chilcott Castillo, Kan-Dobrosky, Eichner, Thakkar: AbbVie employees, may own AbbVie stock.Table: Table. Treatment-emergent Adverse Events (AE)

Clinical and economic burden of extra-articular manifestations in ankylosing spondylitis patients treated with anti-tumor necrosis factor agents

Objective:To assess concomitant extra-articular manifestation (EAM) rates in patients with ankylosing spondylitis (AS) treated with anti-tumor necrosis factor (anti-TNF) agents and examine the economic burden of uveitis and inflammatory bowel disease (IBD) in French and German AS patients.Methods:Previous analyses of uveitis and IBD in AS patients treated with infliximab, etanercept or adalimumab were identified in PubMed/Medline (January 2000 to August 2011). A supplemental analysis incorporated more recent adalimumab clinical trial data (ATLAS [NCT00085644] and RHAPSODY [NCT00478660]). For resource utilization/costs associated with EAMs, the search was expanded to general spondyloarthritis (SpA) conditions (i.e., AS, reactive or psoriatic arthritis, psoriatic spondylitis, IBD and undifferentiated SpA). Direct and indirect yearly costs associated with AS-associated uveitis and IBD were estimated based on interviews with French and German clinicians and literature review.Results:The pooled average rate of anterior uveitis (AU) flares for patients treated with anti-TNF therapy in two meta-analyses and supplemental adalimumab clinical trials was 4.9/100-patient-years (PYs). AU rates (per 100-PYs) were 3.4, 3.7 and 5.7 for infliximab (p = 0.26 vs etanercept; p = 0.86 vs adalimumab), adalimumab (p = 0.033 vs etanercept) and etanercept, respectively. IBD flares (per 100-PYs) were 0.2 for infliximab (p < 0.001 vs etanercept; p = 0.18 vs adalimumab), 0.63 for adalimumab (p = 0.009 vs etanercept) and 2.2 for etanercept. No studies assessing EAM-associated resource utilization or costs in AS patients were found. Direct medical costs associated with IBD treatment ranged from €483 (Germany) to €6443 (France). Clinician-estimated AS-related uveitis direct medical costs were €1410 (Germany) and €1812 (France).Conclusions:Clinical data synthesis demonstrated significantly lower AU flare rates with adalimumab vs etanercept and significantly lower IBD rates with both adalimumab and infliximab vs etanercept. Economic analysis indicated substantial costs associated with AU and IBD flares secondary to AS in France and Germany. Future economic evaluations of anti-TNF agents should incorporate EAMs and subsequent treatment costs. Limitations include restricted availability of randomized, placebo-controlled clinical trial data, inclusion of data from open-label studies, lack of real-world (i.e., non-trial-based) EAM rates and a lack of EAM-specific direct and indirect costs with which to compare the results presented herein.

Achievement of European Consensus Programme treatment goals in three clinical trials of adalimumab in moderate-to-severe psoriasis

Achievement of European Consensus Programme treatment goals in three clinical trials of adalimumab in moderate-to-severe psoriasis

Adalimumab in the Treatment of Psoriasis: Pooled Efficacy and Safety Results from Three Pivotal Studies

Adalimumab, a fully human monoclonal antibody, binds to and neutralizes tumor necrosis factor. To provide an integrated review of efficacy and safety from adalimumab clinical trials in psoriasis. Pooled analyses were conducted of three placebo-controlled clinical trials of adalimumab (40 mg every other week) in psoriasis patients. The primary efficacy measure was the Psoriasis Area Severity Index (PASI). The Physician's Global Assessment (PGA) was also assessed. At Week 16, mean percentage PASI improvement was 78.3% for adalimumab-treated patients versus 15.1% for placebo-treated patients. A PGA of "Clear" or "Minimal" was achieved in 63.4% of adalimumab-treated patients versus 5.1% of placebo-treated patients. The response to adalimumab was rapid, with significant improvements for adalimumab-treated patients in most efficacy measures by Week 4. Adverse event incidence was similar between treatment groups and consistent with adalimumab safety profiles in other indications. Adalimumab improved psoriasis and was generally safe and well-tolerated.

Adalimumab safety in global clinical trials of patients with Crohnʼs disease

Adalimumab, a fully human anti-tumor necrosis factor (anti-TNF) monoclonal antibody, is approved for the treatment of Crohn's disease (CD) in adults. We evaluated the overall safety profile of adalimumab in global clinical trials in patients with CD. Patients who participated in these trials, which included randomized induction and maintenance trials, Phase IIIb trials, and open-label extension studies, had moderately to severely active CD and were evaluated for safety at regular intervals. Rates of adverse events of interest were assessed per 100-patient-years of adalimumab exposure. Standardized mortality rates and standardized incidence rates (for malignancies) were calculated using population-matched data. As of April 15, 2008, 3160 patients with CD had been treated with adalimumab in clinical trials, representing 3401.9 patient-years of adalimumab exposure. Serious infection was the most frequently reported serious adverse event of interest in the CD trials; abscess (intraabdominal and gastrointestinal related) was the most common serious infection. Low incidences of malignancies, lymphomas, opportunistic infections (including tuberculosis), demyelinating disorders, and lupus-like disorders were reported in the CD trials. The standardized mortality rate for adalimumab-treated patients with CD, 0.44 (95% confidence interval [CI], 0.12-1.12), is less than the rate of 1.52 (95% CI, 1.32-1.74) reported in a recent meta-analysis of patients with CD. The safety profile of adalimumab in patients with CD was similar to that of other TNF antagonists in CD populations, and the rates of adverse events were comparable to other approved indications for adalimumab spanning >10 years of clinical observation. No new safety signals were identified.

Relationship between Clinical Response to Therapy and Health-Related Quality of Life Outcomes in Patients with Moderate to Severe Plaque Psoriasis

Background: Health-related quality of life (HRQOL) outcomes are associated with clinical response to treatment in psoriasis. However, the association between HRQOL outcomes and more substantial degrees of Psoriasis Area and Severity Index (PASI) response and physician and patient global ratings remains ill defined. Objective: This study examined the relationship between achieving a 75% or ≧90% improvement in PASI and HRQOL outcome measures. Methods: Secondary analyses were completed using data for 1,469 patients with moderate to severe plaque psoriasis from two adalimumab clinical trials. HRQOL was measured via the Dermatology Life Quality Index (DLQI) and the Short Form 36 (SF 36) Health Survey. Clinical response was assessed by the PASI, physician’s global assessment and patient’s global assessment status scores. Clinical response was categorized into 6 groups based on PASI response: <25% (n = 332); 25 to <50% (n = 137); 50 to <75% (n = 170); 75 to <90% (n = 288); 90 to <100% (n = 255), and 100% (n = 192). Analysis of covariance models compared baseline measures and 16-week changes in HRQOL scores. Results: Statistically significant differences were observed between PASI response groups in DLQI total scores and in SF 36 summary and scale scores (p < 0.0001). The PASI 100 and PASI 90 to <100 groups demonstrated a >10-point decrease in DLQI total scores. Moreover, these changes were statistically significantly greater than those observed for the PASI 75 to <90 group (p < 0.001) and the other PASI response groups (p < 0.001). For the SF 36, the greatest changes were observed in the PASI 75 to <90, PASI 90 to <100 and PASI 100 groups, which all had improvements of >4 points in the Mental Component and Physical Component Summary (MCS and PCS) scores. Statistically significantly greater differences in DLQI total and SF 36 summary and scale scores were also observed between patient’s global assessment categories (p < 0.0001) and between physician’s global assessment categories (p < 0.0001). Conclusion: Improvement in PASI response of >75% corresponded to improvements in HRQOL outcome measures for patients with moderate to severe psoriasis. PASI 90 or 100 responders had greater improvements in DLQI total score than PASI 75 responders.

Screening outcomes for latent tuberculosis in worldwide adalimumab clinical trials

Screening outcomes for latent tuberculosis in worldwide adalimumab clinical trials