Body Mass Index and Systemic Corticosteroid Use as Indicators of Disease Burden and Their Influence on the Safety Profile of Certolizumab Pegol Across Indications

Vivian Bykerk¹, Andrew Blauvelt ², Jeffrey Curtis ³, Cécile Gaujoux-Viala ⁴, Tore K. Kvien ⁵, William J. Sandborn ⁶, Kevin Winthrop ⁷, Christina Popova ⁸ and Xavier Mariette ⁹, ¹Hospital for Special Surgery, New York City, NY, ²Oregon Medical Research Center, Portland, OR, USA, Portland, OR, ³University of Alabama at Birmingham, Birmingham, AL, ⁴Nîmes University Hospital, Nîmes, France, ⁵Diakonhjemmet Hospital, Oslo, Norway, ⁶University of California, La Jolla, CA, ⁷Oregon Health and Science University, Portland, OR, ⁸UCB Pharma, Brussels, Belgium, ⁹Center for Immunology of Viral Infections and Autoimmune Diseases, Assistance Publique – Hôpitaux de Paris, Hôpitaux Universitaires Paris-Sud, Le Kremlin-Bicêtre, Université Paris Sud, INSERM, Paris, France

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: body mass, certolizumab pegol, corticosteroids, infection and safety

Session Information

Date: Tuesday, November 12, 2019

Title: Epidemiology & Public Health Poster III: OA, Gout, & Other Diseases

Session Type: Poster Session (Tuesday)

Session Time: 9:00AM-11:00AM

Background/Purpose: Certolizumab pegol (CZP) is an anti-TNF drug approved for rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), psoriasis (PSO) and Crohn’s disease (CD). Older age, comorbidities and corticosteroid (CS) use have been linked to increased risk of serious infectious events (SIEs) in CZP-treated patients (pts) with RA.¹ However, the impact of overall disease burden on the risk of serious adverse events (SAEs) has not been fully examined for other CZP indications. High body mass index (BMI) has been linked to systemic inflammation and comorbidity risk.^2,3 Greater disease burden in these pts may lead to increased CS use – a known risk factor for SAEs.¹ This study aimed to examine the contribution of BMI and CS use to the risk of SIEs, malignancies and major adverse cardiovascular events (MACE) in CZP-treated pts across indications.

Methods: Safety data were pooled across 49 CZP clinical trials (27 RA, 1 axSpA, 1 PsA, 5 PSO, 15 CD). SAEs of potential concern were medically reviewed by an external expert committee using predefined case rules.⁴ Incidence rates (IR) were calculated per 100 pt‑years (PY). Multivariate Cox modeling was used to estimate relative risk (hazard ratio [HR]) of time to first SIE, malignancy or MACE by baseline BMI (< 18.5, 18.5–< 25, 25–< 30, ≥30 kg/m²) and CS use (yes, no). The model was adjusted for baseline age, sex, disease duration, methotrexate (MTX) use, prior anti-TNF drug use, and CZP indication.

Results: Across indications, 11,317 pts received CZP (21,695 PY total exposure; max: 7.8 years [yrs]; exposure for RA: 13,542 PY; axSpA: 978 PY; PsA: 1,316 PY; PSO: 1,481 PY; CD: 4,378 PY). Mean BMI was 27.8 kg/m² in RA, 27.6 kg/m² in axSpA, 29.8 kg/m² in PsA, 30.1 kg/m² in PSO, and 24.0 kg/m² in CD. Overall, 4,132 pts (37%) used CS at baseline, more so in RA (46%) and axSpA (51%). Across indications, IRs were 0.82/100 PY for all malignancies (0.66/100 PY excluding non-melanoma skin cancer [NMSC]), 0.47/100 PY for MACE, and 3.62/100 PY for SIEs. According to the Cox model, age ≥45 yrs, disease duration < 1 yr (compared with ≥5 yrs), and no MTX use were risk factors for malignancies (including NMSCs); BMI and CS use did not have a detectable impact (Table). MACE risk was higher in RA and PsA; BMI ≥30 kg/m² was a risk factor for MACE, in addition to age ≥45 yrs and male sex (Table). Compared with RA, SIE risk was higher in CD and lower in PSO and PsA; key risk factors included age ≥65 yrs, disease duration ≥10 yrs and CS use. Without CS use, BMI did not impact SIE risk, but among CS users, SIE risk was higher for obese pts (Table)

Conclusion: In CZP-treated pts across indications, malignancy risk was not influenced by BMI or CS use. As expected, obesity and CS use increased the risk of MACE. The SIE risk associated with CS use was compounded in obese pts, which may reflect the contribution of comorbidities, disease activity or other factors not examined here.

References:

1. Curtis JR. Arthritis Res Ther 2017;19:276; 2. Pérez de Heredia F. Proc Nutr Soc 2012;71:332–8; 3. Harpsøe MC. Int J Epidemiol 2014;43:843–55; 4. Curtis JR. RMD Open 2019;5:e000942.

Disclosure: V. Bykerk, AbbVie, 5, Amgen, 1, 2, 3, 5, 8, Brainstorm Therapeutics, 1, 2, 3, 5, 8, Bristol-Myers Squibb, 5, Genentech, 5, Gilead, 5, NIH, 2, Pfizer, 1, 2, 3, 5, 8, Regeneron, 5, Regeneron Pharmaceuticals, Inc, 5, Sanofi, 5, Sanofi/Genzyme-Regeneron, 5, Sanofi-Genzyme/Regeneron, 1, 2, 3, 5, 8, Scipher, 1, 2, 3, 5, 8, The Cedar Hill Foundation, 9, UCB, 1, 2, 3, 5, 8, UCB Pharma, 5; A. Blauvelt, AbbVie, 2, 5, 8, Aclaris, 2, 5, 8, Akros, 2, 5, 8, Allergan, 2, 5, 8, Almirall, 2, 5, 8, Amgen, 2, 5, 8, Arena, 2, 5, 8, Boehringer Ingelheim, 2, 5, 8, Bristol-Myers Squibb, 2, 5, 8, Celgene, 2, 5, 8, Dermavant, 2, 5, 8, Dermira Inc., 5, 8, Dermira, Inc, 2, 5, Dermira, Inc., 2, 5, Eli Lilly and Co, 2, 5, Eli Lilly and Company, 5, 8, Galderma, 2, 5, Genentech/Roche, 2, 5, 8, GlaxoSmithKline, 2, 5, 8, Janssen, 2, 5, 8, Leo, 2, 5, 8, Meiji, 2, 5, 8, Merck, 5, 8, Merck Sharp & Dohme, 2, 5, Novartis, 2, 5, 8, Pfizer, 2, 5, 8, Purdue Pharma, 2, 5, 8, Regeneron, 2, 5, 8, Revance, 2, 5, 8, Sandoz, 2, 5, 8, Sanofi Genzyme, 2, 5, 8, Sienna Pharmaceuticals, 2, 5, 8, Sun Pharma, 5, 8, Sun Pharmaceutical Industries, Inc, 2, 5, UCB Pharma, 2, 5, 8, Valeant, 2, 5, 8, Vidac, 2, 5, 8; J. Curtis, AbbVie, 2, 5, Abbvie, 2, 5, AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Lilly, Janssen, Myriad, Pfizer, Regeneron, Roche, and UCB, 2, 5, Amgen, 2, 5, Amgen Inc., 2, 5, BMS, 2, 5, Bristol-Myers Squibb, 2, 5, Corrona, 2, 5, Crescendo, 2, 5, Eli Lilly, 2, 5, Eli Lilly and Company, 2, 5, Genentech, 2, 5, Janseen, 5, Janssen, 2, 5, Janssen Research & Development, LLC, 2, Lilly, 2, 5, Myriad, 2, 5, Patient Centered Outcomes Research Insitute (PCORI), 2, Pfizer, 2, 5, Radius Health, Inc., 9, Regeneron, 2, 5, Roche, 2, 3, 5, Roche/Genentech, 5, UCB, 2, 5; C. Gaujoux-Viala, AbbVie, 5, 8, Amgen, 5, 8, Bristol-Myers Squibb, 5, 8, Celgene, 5, 8, Eli Lilly, 5, 8, Gilead, 5, 8, Janssen, 5, 8, Medac, 5, 8, Merck-Serono, 5, 8, Nordic Pharma, 5, 8, Novartis, 5, 8, Pfizer, 5, 8, Roche, 5, 8, Sandoz, 5, 8, Sanofi, 5, 8, UCB Pharma, 5, 8; T. Kvien, Biogen, 5, 8, Bristol-Myers Squibb, 5, 8, Boehringer Ingelheim, 5, 8, Celltrion, 5, 8, Eli Lilly, 5, 8, Epirus, 5, 8, Hospira, 5, 8, Merck-Serono, 5, 8, Novartis, 5, 8, Orion Pharma, 5, 8, Pfizer, 5, 8, Sandoz, 5, 8, UCB Pharma, 5, 8; W. Sandborn, Atlantic Healthcare Limited, 2, AbbVie, 2, 5, Amgen, 2, 5, Celgene/Receptos, 2, Genentech, 2, 5, Eli Lilly, 2, 5, Gilead Sciences, 2, 5, Janssen, 2, 5, Takeda, 2, 5, Allergan, 5, Boehringer Ingelheim, 5, Celgene, 5, Conatus, 5, Cosmo, 5, Escalier Biosciences, 4, 5, Ferring, 5, Gossamer Bio, 4, 5, Miraca Life Sciences, 5, Nivalis Therapeutics, 5, Novartis Nutrition Science Partners, 5, Oppilan Pharma, 4, 5, Otsuka, 5, Paul Hastings, 5, Pfizer, 5, Precision IBD, 4, 5, Progenity, 4, 5, Prometheus Laboratories, 5, Ritter Pharmaceuticals, 4, 5, Robarts Clinical Trials (owned by Health Academic Research Trust or HART), 5, Salix, 5, Shire, 5, Seres Therapeutics, 5, Sigmoid Biotechnologies, 5, Tigenix, 5, Tillotts Pharma, 5, UCB Pharma, 5, Vivelix, 5; K. Winthrop, AbbVie, 5, Abbvie, 5, Bristol-Myers Squibb, 2, 5, Eli Lilly, 5, Galapagos, 5, Galapagos NV, 5, Gilead, 5, Gilead Sciences, Inc., 5, GSK, 5, Lilly, 5, Pfizer, 2, 5, Roche, 5, UCB, 5, UCB Pharma, 5, UCB Pharma, Pfizer, Bristol-Myers Squibb, Eli Lilly, AbbVie, and Roche., 2, 5; C. Popova, UCB Pharma, 3; X. Mariette, Biogen, 2, Bristol-Myers Squibb, 5, GlaxoSmithKline, 5, Janssen, 5, LFB Pharmaceuticals, 5, OSE Immunotherapeutics, 2, Pfizer, 2, 5, UCB Pharma, 5, 8.

To cite this abstract in AMA style:

Bykerk V, Blauvelt A, Curtis J, Gaujoux-Viala C, Kvien T, Sandborn W, Winthrop K, Popova C, Mariette X. Body Mass Index and Systemic Corticosteroid Use as Indicators of Disease Burden and Their Influence on the Safety Profile of Certolizumab Pegol Across Indications [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/body-mass-index-and-systemic-corticosteroid-use-as-indicators-of-disease-burden-and-their-influence-on-the-safety-profile-of-certolizumab-pegol-across-indications/. Accessed .

« Back to 2019 ACR/ARP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/body-mass-index-and-systemic-corticosteroid-use-as-indicators-of-disease-burden-and-their-influence-on-the-safety-profile-of-certolizumab-pegol-across-indications/