SAT0605 BODY MASS INDEX AND SYSTEMIC CORTICOSTEROID USE AS INDICATORS OF DISEASE BURDEN AND THEIR INFLUENCE ON THE SAFETY PROFILE OF CERTOLIZUMAB PEGOL ACROSS INDICATIONS
Authors: Vivian Bykerk, Andrew Blauvelt, Jeffrey Curtis, Cecile Gaujoux-Viala, Tore K. Kvien, William Sandborn, Kevin Winthrop, Christina Popova, Xavier Mariette
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> 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, comorbidity burden and corticosteroid (CS) use have been linked to increased risk of serious infectious events (SIEs) in CZP-treated patients (pts) with RA.<sup>1</sup> 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 associated with systemic inflammation and greater comorbidity risk.<sup>2,3</sup> Greater disease burden in these pts may lead to increased CS use – a known risk factor for SAEs.<sup>1</sup> <h3>Objectives:</h3> 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. <h3>Methods:</h3> 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. 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 (&lt;18.5, 18.5–&lt;25, 25–&lt;30, ≥30 kg/m<sup>2</sup>) 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. <h3>Results:</h3> 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/m<sup>2</sup> in RA, 27.6 kg/m<sup>2</sup> in axSpA, 29.8 kg/m<sup>2</sup> in PsA, 30.1 kg/m<sup>2</sup> in PSO, and 24.0 kg/m<sup>2</sup> in CD. Overall, 4,132 pts (37%) took CS at baseline, more so in RA (46%) and axSpA (51%). Across indications, IRs were 0.82/100 PY for all malignancies (IR for malignancies excluding non-melanoma skin cancer [NMSC] was 0.66/100 PY), 0.47/100 PY for MACE, and 3.62/100 PY for SIEs. According to the Cox model, age ≥45 yrs, disease duration &lt;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 (<b>Table</b>). MACE risk was higher in RA and PsA; BMI ≥30 kg/m<sup>2</sup> was a risk factor for MACE, in addition to age ≥45 yrs and male sex (<b>Table</b>). 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 (<b>Table</b>). <h3>Conclusion:</h3> 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. <h3>References</h3> [1] Curtis J. Arthritis Res Ther 2017;19:276; 2. Pérez de Heredia F. Proc Nutr Soc 2012;71:332–8; 3. Harpsøe M. Int J Epidemiol 2014;43:843–55. <h3>Acknowledgement:</h3> We thank the patients who participated. This study was funded by UCB Pharma, medical writing by Emma Phillips, Costello Medical, UK. <h3>Disclosure of Interests:</h3> Vivian Bykerk Grant/research support from: Mallinckrodt, BMS, Crescendo Biosciences, Sanofi/Regeneron., Consultant for: Amgen, Pfizer, UCB, Scipher, Sanofi/Genzyme/Regeneron, Andrew Blauvelt Grant/research support from: AbbVie, Aclaris, Akros, Allergan, Almirall, Amgen, Boehringer Ingelheim, Celgene, Dermavant, Dermira Inc, Eli Lilly and Company, Galderma, Genentech/Roche, GlaxoSmithKline, Janssen, LEO, Meiji, Merck Sharp &amp; Dohme, Novartis, Pfizer, Purdue Pharma, Regeneron, Revance, Sandoz, Sanofi Genzyme, Sienna Pharmaceuticals, Sun Pharmaceuticals, UCB Pharma, Valeant, Vidac, Consultant for: AbbVie, Aclaris, Akros, Allergan, Almirall, Amgen, Boehringer Ingelheim, Celgene, Dermavant, Dermira Inc., Eli Lilly and Company, Galderma, Genentech/Roche, GlaxoSmithKline, Janssen, LEO, Meiji, Merck Sharp &amp; Dohme, Novartis, Pfizer, Purdue Pharma, Regeneron, Revance, Sandoz, Sanofi Genzyme, Sienna Pharmaceuticals, Sun Pharmaceuticals, UCB Pharma, Valeant, Vidac., Speakers bureau: Janssen, Regeneron, Sanofi Genzyme, Jeffrey Curtis: None declared, Cecile Gaujoux-Viala Consultant for: Speaking and/or consulting fees from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Merck-Serono, Medac, Nordic Pharma, Novartis, Pfizer, Roche, Sandoz, Sanofi and UCB Pharma., Speakers bureau: Speaking and/or consulting fees from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Merck-Serono, Medac, Nordic Pharma, Novartis, Pfizer, Roche, Sandoz, Sanofi and UCB Pharma., Tore K. Kvien Grant/research support from: AbbVie, BMS, MSD, Pfizer, Roche and UCB., Consultant for: AbbVie, Biogen, BMS, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Hospira, Merck-Serono, MSD, Novartis, Oktal, Orion Pharma, Pfizer, Roche, Sandoz, Sanofi, Mylan and UCB, Speakers bureau: AbbVie, Biogen, BMS, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Hospira, Merck-Serono, MSD, Novartis, Oktal, Orion Pharma, Pfizer, Roche, Sandoz, Sanofi and UCB, William Sandborn Shareholder of: Stock options from Escalier Biosciences, Gossamer Bio, Oppilan Pharma, Precision IBD, Progenity and Ritter Pharmaceuticals, Grant/research support from: Research grants from Atlantic Healthcare Limited, AbbVie, Amgen, Celgene/Receptos, Genentech, Gilead Sciences, Janssen, Lilly and Takeda, Consultant for: Consulting fees from AbbVie, Allergan, Amgen, Boehringer Ingelheim, Celgene, Conatus, Cosmo, Escalier Biosciences, Ferring, Genentech, Gilead, Gossamer Bio, Janssen, Lilly, Miraca Life Sciences, Nivalis Therapeutics, Novartis Nutrition Science Partners, Oppilan Pharma, Otsuka, Paul Hastings, Pfizer, Precision IBD, Progenity, Prometheus Laboratories, Ritter Pharmaceuticals, Robarts Clinical Trials (owned by Health Academic Research Trust or HART), Salix, Shire, Seres Therapeutics, Sigmoid Biotechnologies, Takeda, Tigenix, Tillotts Pharma, UCB Pharma and Vivelix, Kevin Winthrop Consultant for: Gilead, Galapagos, Eli Lilly and Company, Abbvie, Pfizer, GSK, Christina Popova Employee of: Employee of UCB Pharma., Xavier Mariette Grant/research support from: Servier, Consultant for: AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, Pfizer, UCB Pharma