PYRAMID Registry Research Articles

IMPACT OF TREATMENT RESPONSE WITH ADALIMUMAB ON RISK OF SERIOUS INFECTIONS IN PATIENTS WITH CROHN’S DISEASE: SECONDARY ANALYSIS OF THE PYRAMID REGISTRY

Abstract BACKGROUND AND AIMS Treatment efficacy and safety are primary factors in choosing therapies in patients with Crohn’s disease (CD). However, they can be perceived to be at odds with each other with more potent therapies associated with increased risk of infections. We evaluated the impact of treatment response on the risk of serious infections in adalimumab-treated patients with CD through secondary analysis of the PYRAMID registry. METHODS We included patients with CD who newly started adalimumab in the prospective PYRAMID registry (NCT00524537) and classified them as treatment responders (achieved steroid-free clinical remission based on patient-reported outcomes) vs. non-responders (not in steroid-free clinical remission) at 6m after treatment initiation (landmark). We compared the risk of serious infections between responders vs. non-responders between 6-36m after treatment initiation, through stabilized inverse probability of treatment weighted (IPW) Cox proportional hazards model. RESULTS Of 1515 adalimumab-treated patients with complete data at 6m, 763 (50.4%) were classified as responders (37±13y, 56% female, disease duration, 9.5y). At time of starting adalimumab (baseline), as compared with non-responders, responders were less likely to have moderate to severe symptoms (55.6% vs. 33%), require steroids (45.5% vs. 17.3%) or opiates (6.6% vs. 1.3%), have had prior CD-related surgery (46.5% vs. 35.1%), without any differences in disease location, perianal disease, and prior CD complications. On follow-up, between 6-36m (observation period after 6m landmark), 123 patients experienced a total of 162 serious infections. Of these, 52 responders (6.8%) experienced a serious infection vs. 71 non-responders (9.4%). Approximately, 58% infections were classified as gastrointestinal in origin. On stabilized IPTW through generalized boosting model, responders were 34% less likely to experience serious infections on follow-up compared with non-responders (HR, 0.66; 95% CI, 0.46-0.96). There was no significant difference in risk of serious infections between responders vs. non-responders based on organ site (gastrointestinal infections: HR, 0.61; 95% CI, 0.38-0.99; extra-intestinal infections: HR, 0.61; 95% CI, 0.46-1.30) (p-value for difference in groups = 1.00). Responders were significantly less likely to require corticosteroids on follow-up (1y: 4.4%, 2y: 8.9%, 3y: 9.6%), compared with non-responders (1y: 50.7%, 2y: 51.6% vs. 3y: 51%). CONCLUSIONS Patients with CD who respond to adalimumab have lower risk of developing serious infections, compared with non-responders, after accounting for disease severity. These findings underscore that initiation of advanced therapy for CD may lower the risk of serious infections through effective disease control and avoidance of corticosteroids.

Impact of Treatment Response on Risk of Serious Infections in Patients With Crohn’s Disease: Secondary Analysis of the PYRAMID Registry

Traditional risk factors for serious infections with advanced therapies in patients with Crohn's disease (CD) have been assessed at baseline before starting therapy. We evaluated the impact of treatment response on the risk of serious infections in adalimumab-treated patients with CD through secondary analysis of the PYRAMID registry (NCT00524537). We included patients with CD who initiated adalimumab and classified them as treatment responders (achieved steroid-free clinical remission based on patient-reported outcomes) vs nonresponders (not in steroid-free clinical remission) at 6 months after treatment initiation (landmark). We compared the risk of serious infections between responders vs nonresponders between 6 and 36 months after treatment initiation through stabilized inverse probability of treatment weighting Cox proportional hazards model. Of 1515 adalimumab-treated patients, 763 (50.4%) were classified as responders at 6 months (37 ± 13 y; 56% female; disease duration, 9.5 ± 8.5 y). Compared with nonresponders, responders were less likely to have moderate to severe symptoms (55.6% vs 33%), or require steroids (45.5% vs 17.3%) or opiates (6.6% vs 1.3%) at baseline, without any differences in disease location, perianal disease, and prior CD complications. During follow-up evaluation, using stabilized inverse probability of treatment weighting, responders were 34% less likely to experience serious infections compared with nonresponders (hazard ratio, 0.66; 95% CI, 0.46-0.96). Risk of gastrointestinal and extraintestinal infections was lower in responders vs nonresponders. Patients with CD who respond to adalimumab have a lower risk of developing serious infections compared with nonresponders. These findings underscore that initiation of advanced therapy for CD may lower the risk of serious infections through effective disease control and avoidance of corticosteroids.

Observational data from the adalimumab post‐marketing PYRAMID registry of patients with Crohn's disease who became pregnant: A post hoc analysis

BackgroundPYRAMID was an international post‐marketing registry that aimed to collect data on the long‐term safety and effectiveness of adalimumab treatment per local standard of care in patients with moderately to severely active Crohn's disease (CD). Here, we present post hoc analyses of observational data from patients who became pregnant while participating in this registry and receiving adalimumab.MethodsFrom the subpopulation of patients receiving adalimumab who became pregnant while taking part in PYRAMID, data on patient characteristics, pregnancy outcomes, and complications of pregnancy were analysed retrospectively.ResultsAcross the PYRAMID registry, 293 pregnancies occurred in patients who had gestational adalimumab exposure (average disease duration at last menstrual period: 8.6 years), resulting in 300 pregnancy outcomes. A total of 197 pregnancies (67.2%) were exposed to adalimumab in all trimesters per physician's decision. Of the known reported outcomes (96.3%), 81.7% (236/289) were live births, 10.4% (30/289) were spontaneous abortions, 4.8% (14/289) elective terminations, 2.8% (8/289) ectopic pregnancies, and 0.3% (1/289) was a stillbirth. Congenital malformations (pulmonary valve stenosis and tricuspid valve incompetence) were reported in one infant. In addition to the pregnancy outcomes described above, 23 complications of pregnancy were reported in 20 patients.ConclusionsThis analysis showed that adalimumab treatment in patients with CD, who became pregnant whilst participating in the PYRAMID registry, contributed no additional adverse effects during the pregnancy course or on pregnancy outcomes.

Adalimumab Effectiveness Up to Six Years in Adalimumab-naïve Patients with Crohn's Disease: Results of the PYRAMID Registry.

BackgroundPYRAMID was an international multicenter, noninterventional, postmarketing registry assessing long-term safety and effectiveness of adalimumab (Humira), as used in routine clinical practice.MethodsAdult patients with moderately to severely active Crohn’s disease with or without prior adalimumab experience were enrolled in the registry and followed for up to 6 years. Effectiveness measurements included the Physician’s Global Assessment (PGA, a composite of Harvey Bradshaw Index [HBI] and rectal bleeding score), clinical remission (HBI < 5), Short Inflammatory Bowel Disease Questionnaire (SIBDQ), and Work Productivity and Activity Impairment (WPAI) questionnaire. Data were reported for adalimumab-naïve patients and analyzed by baseline immunomodulator use and disease duration.ResultsThis study evaluated 2057 adalimumab-naïve patients. Mean PGA improved from 7.5 (baseline) to 3.9 (year 1) and 3.3 (year 6). The proportion of patients in HBI remission increased from 29% (573 of 1969; baseline) to 68% (900 of 1331; year 1) and 75% (625 of 831; year 6). Patients stratified by baseline immunomodulator use had similar HBI remission rates; patients with disease duration <2 years achieved numerically higher HBI remission rates than patients with longer disease duration. Patient-reported SIBDQ and WPAI scores improved at year 1; all WPAI subscore improvements were clinically meaningful (≥7% point change) at year 1 and maintained through year 6. Serious infections were reported in 11.1% of patients; incidence rates of malignancies, lymphoma, and demyelinating disorders were low.ConclusionAdalimumab therapy, as used in routine clinical practice, improved physician-reported and patient-reported disease outcomes and remission rates for up to 6 years. No new safety signals were observed.

Sa1808 - Long-Term Effectiveness and Safety of Adalimumab Based on Crohn's Disease Duration: Results from the Pyramid Registry

Sa1808 - Long-Term Effectiveness and Safety of Adalimumab Based on Crohn's Disease Duration: Results from the Pyramid Registry

P757 Long-term effectiveness and safety of adalimumab based on Crohn’s disease duration: Results from the PYRAMID registry

P757 Long-term effectiveness and safety of adalimumab based on Crohn’s disease duration: Results from the PYRAMID registry

PYRAMID Registry: Long-term Safety of Adalimumab by Age in Patients With Crohnʼs Disease

Introduction: The global post-marketing observational registry PYRAMID assessed the long-term safety and effectiveness of adalimumab (ADA) as used in routine clinical practice in patients (pts) with moderate to severe Crohn's disease (CD). Methods: Enrolled Pts were newly prescribed or currently receiving ADA according to local product label; pts were followed up to 6 yrs. This analysis assessed the long-term safety of ADA by age subgroups (< 40, 40-59, and ≥60 yrs) at registry enrolment (baseline [BL]). Registry treatment-emergent (TE) adverse events (AEs), (any event with onset on/after first dose of ADA in the registry up to 70 days after last ADA injection) are reported as events per 100 patient-yrs (PY). Results: 5025 pts in the registry received at least one dose of ADA and included in the analysis; at BL, 2981 pts (59.3%) were < 40 yrs (female, 57.1%; median age, 29.0 yrs; median CD duration, 7.0 yrs), 1717 pts (34.2%) were 40-59 yrs (female, 57.8%; median age, 47.0 yrs; median CD duration, 13.0 yrs) and 327 pts (6.5%) were ≥60 yrs (female, 52.9%; median age, 64.0 yrs; median CD duration, 13.5 yrs). Of those ≥60 yrs at BL, 23/327 (7.0%) were ≥75 yrs. Cumulative registry ADA exposure by BL age groups was 9681.1 PY (< 40 yrs), 6009.3 PY (40-59 yrs) and 990.0 PY (≥60 yrs). Approximately 46-52% of pts were receiving ADA monotherapy (without immunomodulators or corticosteroids) at BL across age groups. Rates of any registry TEAEs, including serious AEs and AEs of special interest, by age groups at BL are shown in Table 1. Similar rates of registry TE serious infections and opportunistic infections were observed across younger age groups, but numerically higher in the ≥60 yrs group. Rates of any registry TE malignancies and non-melanoma skin cancer were significantly higher in older pts (≥60 yrs at BL). There was no event of lymphoma reported in aged ≥60 yrs at BL group; however, during the follow-up in the registry, 3 pts classified in the 40-59 yrs at BL age group were diagnosed with lymphoma when they were ≥60 yrs. No pts in the ≥60 yrs group reported active/latent tuberculosis.Table: Table. Cumulative incidence of registry treatment-emergent adverse events (TEAEs)Conclusion: Long-term treatment with ADA was well tolerated in pts with moderate to severe CD, irrespective of patient age. Rate of exposure-adjusted registry TEAEs (per 100 PY) was generally higher in older (≥60 yrs) compared to younger pts (< 60 yrs); however, no new safety signals were identified in this age group.

Adalimumab Long-term Effectiveness in Adalimumab-Naive Patients With Crohnʼs Disease: Final Data From PYRAMID Registry

Adalimumab Long-term Effectiveness in Adalimumab-Naive Patients With Crohnʼs Disease: Final Data From PYRAMID Registry

PYRAMID Registry: Long-term Safety and Effectiveness of Adalimumab by Baseline Immunomodulator Use in Patients With Crohnʼs Disease

PYRAMID Registry: Long-term Safety and Effectiveness of Adalimumab by Baseline Immunomodulator Use in Patients With Crohnʼs Disease

Mo1661 - Adalimumab Long-Term Effectiveness in Adalimumab-Naïve Patients with Crohn's Disease: Final Data from Pyramid Registry

Mo1661 - Adalimumab Long-Term Effectiveness in Adalimumab-Naïve Patients with Crohn's Disease: Final Data from Pyramid Registry

616 - Long-Term Safety of Adalimumab in Patients with Crohn's Disease: Final Data from Pyramid Registry

616 - Long-Term Safety of Adalimumab in Patients with Crohn's Disease: Final Data from Pyramid Registry

P353 Long-term safety of adalimumab in patients with Crohn's disease: final data from PYRAMID registry

P353 Long-term safety of adalimumab in patients with Crohn's disease: final data from PYRAMID registry

P669 Adalimumab long-term effectiveness in adalimumab-naïve patients with Crohn's disease: final data from PYRAMID registry

P669 Adalimumab long-term effectiveness in adalimumab-naïve patients with Crohn's disease: final data from PYRAMID registry

Tu1914 PYRAMID Registry: An Observational Study of Adalimumab in Crohn's Disease: Results at Year 7

Tu1914 PYRAMID Registry: An Observational Study of Adalimumab in Crohn's Disease: Results at Year 7

DOP047. PYRAMID registry: an observational study of adalimumab in Crohn’s disease—results at year 7

DOP047. PYRAMID registry: an observational study of adalimumab in Crohn’s disease—results at year 7

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

P319. Adalimumab long-term effectiveness in adults with Crohn's Disease: Observational data from the PYRAMID registry

P319. Adalimumab long-term effectiveness in adults with Crohn's Disease: Observational data from the PYRAMID registry

DOP036. PYRAMID registry: an observational study of adalimumab in Crohn's disease: Results at year 6

DOP036. PYRAMID registry: an observational study of adalimumab in Crohn's disease: Results at year 6

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)

Long-term Effectiveness of Adalimumab in Crohnʼs Disease: Observational Data from the PYRAMID Registry

Purpose: Adalimumab (ADA), an anti-tumor necrosis factor agent, is approved for the treatment of moderately to severely active Crohn's disease (CD). Methods: We assessed long-term effectiveness of ADA in patients enrolled in an observational study initiated in 2007, PYRAMID. ADA was prescribed according to local product labels, and patients were followed for 6 years. Effectiveness measures assessed include Physician's Global Assessment (PGA, composite of Harvey-Bradshaw Index and a rectal bleeding score), Short Inflammatory Bowel Disease Questionnaire (SIBDQ), and four components of the Work Productivity and Activity Impairment Questionnaire (WPAI): absenteeism, presenteeism, total work productivity impairment (TWPI), and total activity impairment (TAI). These effectiveness analyses are interim in nature, and results are summarized with descriptive statistics for patients who were naïve to adalimumab therapy at the time of study enrollment. Results: As of December 1, 2012, 5,061 patients have been enrolled. Forty-one percent (2095/5061) of patients were ADA-naïve at the time of enrollment. Mean age of ADA-naive patients was 37 years, mean CD duration was 10 years, 58% were women, and 96% were white. Mean scores for PGA improved from baseline to years 1, 2, 3, and 4 for new ADA users. Clinically meaningful improvements in mean scores for SIBDQ and WPAI (absenteeism, presenteeism, TWPI, and TAI) were maintained over 4 years (Table).Table: Table. Efficacy measures for ADA-naïve patientsConclusion: In this worldwide observational study of ADA use in routine clinical practice, clinically meaningful improvements in disease activity, work productivity, and activity impairment were seen in patients with CD 1 year after initiation of ADA therapy. These improvements were maintained over a 4-year assessment period. Disclosure - EV Loftus Jr: Financial support for research: AbbVie, Amgen, Braintree, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Janssen Biotech, Millenium-Takeda, Pfizer, Santarus, Shire, UCB. Consultancy: AbbVie, Cubist, Elan, Eisai, Given, Hospira, Ironwood, Janssen Biotech, UCB. G D'Haens: Study Investigator and Consultant - AbbVie; CME events/Educational Grants - AbbVie. W Reinisch: Consultant/Advisory Committee - AbbVie, Aesca, Centocor, Genentech, Novartis, Schering-Plough, UCB. Consultant/Speaker - Ferring. J Satsangi: None. R Panaccione: Advisory Board - AbbVie, Amgen, Aptalis, AstraZeneca, Baxter, Bristol-Myers Squibb, Centocor, Eisai, Ferring, Elan, GlaxoSmithKline, Janssen, Merck, Pfi zer, Schering-Plough, Shire, UCB, Warner Chilcott; Consultant - AbbVie, Amgen, Aptalis, AstraZeneca, Baxter, Bristol-Myers Squibb, Centocor, Eisai, Elan, Ferring, GlaxoSmithKline, Jansen, Merck, Pfizer, Schering-Plough, Shire, UCB, Warner Chilcott; Research/Educational Support - AbbVie, Bristol-Myers Squibb, Centocor, Elan, Ferring, Janssen, Millennium, Schering-Plough, Proctor & Gamble; Speaker - AbbVie, AstraZeneca, Centocor, Elan, Janssen, Prometheus, Schering-Plough, Shire, Warner Chilcott. R Thakkar, S Eichner, M Castillo, N Kan-Dobrosky, PM Mulani, J Chao, M Skup: Employee & Shareholder - AbbVie.