CIMZIA^® (certolizumab pegol): Incidence of serious adverse events in CIMZIA clinical trials (per 100 patient-years)^1,5

	CIMZIA	Placebo
TUBERCULOSIS (IN COMPLETED AND ONGOING CLINICAL STUDIES*)	0.61 (n=5118)	0 (n=1563)^†
MALIGNANCIES (IN CLINICAL TRIALS*)	0.5 (0.4-0.7)^‡ (n=4650)	0.6 (0.1-1.7)^‡ (n=1319)
LYMPHOMA (IN RA CLINICAL TRIALS)	0.09 (0.02-0.27)^‡ (n=2367)	0 (n=647)

Including other investigational uses.
Includes patients from placebo arms from phase 2 and 3 controlled clinical trials in RA and Crohn's disease.
Numbers in parentheses represent a 95% confidence interval.

See Warnings and Precautions, including Boxed Warning, regarding tuberculosis, malignancies, and lymphoma

In the controlled RA studies, there were more new cases of serious infection adverse reactions in the CIMZIA treatment groups compared to the placebo groups (0.06 per patient-year for all CIMZIA doses vs 0.02 per patient-year for placebo)¹
Incidence of serious infections during controlled CD clinical studies was 3% per patient-year for patients treated with CIMZIA and 1% for placebo¹
Cases of new or worsening congestive heart failure have been reported with TNF blockers, including CIMZIA¹
In controlled trials in CD and other investigational uses, there was one case of lymphoma among 2657 CIMZIA patients¹

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Indications

CIMZIA is indicated for the treatment of adults with moderately to severely active rheumatoid arthritis (RA)
CIMZIA is indicated for the treatment of adult patients with active psoriatic arthritis (PsA)
CIMZIA is indicated for the treatment of adult patients with active ankylosing spondylitis (AS)
CIMZIA is indicated for reducing signs and symptoms of Crohn's disease (CD) and maintaining clinical response in adult patients with moderately to severely active disease who have had an inadequate response to conventional therapy
CIMZIA is indicated for the treatment of adults with moderate-to-severe plaque psoriasis (PSO) who are candidates for systemic therapy or phototherapy
CIMZIA is indicated for the treatment of adults with active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation

Important Safety Information

contraindications

CIMZIA is contraindicated in patients with a history of hypersensitivity reaction to certolizumab pegol or to any of the excipients. Reactions have included angioedema, anaphylaxis, serum sickness, and urticaria.

serious infections

Patients treated with CIMZIA are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.

Discontinue CIMZIA if a patient develops a serious infection or sepsis.

Reported infections include:

Active tuberculosis (TB), including reactivation of latent TB. Patients with TB have frequently presented with disseminated or extrapulmonary disease. Test patients for latent TB before CIMZIA use and during therapy. Initiate treatment for latent TB prior to CIMZIA use.
Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis. Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized, disease. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Consider empiric anti-fungal therapy in patients at risk for invasive fungal infections who develop severe systemic illness.
Bacterial, viral, and other infections due to opportunistic pathogens, including Legionella and Listeria.

Carefully consider the risks and benefits of treatment with CIMZIA prior to initiating therapy in the following patients: with chronic or recurrent infection; who have been exposed to TB; with a history of opportunistic infection; who resided in or traveled in regions where mycoses are endemic; with underlying conditions that may predispose them to infection. Monitor patients closely for the development of signs and symptoms of infection during and after treatment with CIMZIA, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy.

Do not start CIMZIA during an active infection, including localized infections.
Patients older than 65 years, patients with co-morbid conditions, and/or patients taking concomitant immunosuppressants may be at greater risk of infection.
If an infection develops, monitor carefully and initiate appropriate therapy.

malignancy

Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, of which CIMZIA is a member. CIMZIA is not indicated for use in pediatric patients.

Consider the risks and benefits of CIMZIA treatment prior to initiating or continuing therapy in a patient with known malignancy.
In clinical trials, more cases of malignancies were observed among CIMZIA-treated patients compared to control patients.
In CIMZIA clinical trials, there was an approximately 2-fold higher rate of lymphoma than expected in the general U.S. population. Patients with rheumatoid arthritis, particularly those with highly active disease, are at a higher risk of lymphoma than the general population.
Malignancies, some fatal, have been reported among children, adolescents, and young adults being treated with TNF blockers. Approximately half of the cases were lymphoma, while the rest were other types of malignancies, including rare types associated with immunosuppression and malignancies not usually seen in this patient population.
Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers, including CIMZIA. These cases have had a very aggressive disease course and have been fatal. The majority of reported TNF blocker cases have occurred in patients with Crohn’s disease or ulcerative colitis, and the majority were in adolescent and young adult males. Almost all of these patients had received treatment with azathioprine or 6-mercaptopurine concomitantly with a TNF blocker at or prior to diagnosis. Carefully assess the risks and benefits of treating with CIMZIA in these patient types.
Cases of acute and chronic leukemia were reported with TNF blocker use.

heart failure

Worsening and new onset congestive heart failure (CHF) have been reported with TNF blockers. Exercise caution and monitor carefully.

hypersensitivity

Angioedema, anaphylaxis, dyspnea, hypotension, rash, serum sickness, and urticaria have been reported following CIMZIA administration. If a serious allergic reaction occurs, stop CIMZIA and institute appropriate therapy. The needle shield inside the removable cap of the CIMZIA prefilled syringe contains a derivative of natural rubber latex which may cause an allergic reaction in individuals sensitive to latex.

hepatitis b virus reactivation

Use of TNF blockers, including CIMZIA, may increase the risk of reactivation of hepatitis B virus (HBV) in patients who are chronic carriers. Some cases have been fatal.
Test patients for HBV infection before initiating treatment with CIMZIA.
Exercise caution in patients who are carriers of HBV and monitor them before and during CIMZIA treatment.
Discontinue CIMZIA and begin antiviral therapy in patients who develop HBV reactivation. Exercise caution when resuming CIMZIA after HBV treatment.

neurologic reactions

TNF blockers, including CIMZIA, have been associated with rare cases of new onset or exacerbation of central nervous system and peripheral demyelinating diseases, including multiple sclerosis, seizure disorder, optic neuritis, peripheral neuropathy, and Guillain-Barré syndrome.

hematologic reactions

Rare reports of pancytopenia, including aplastic anemia, have been reported with TNF blockers. Medically significant cytopenia has been infrequently reported with CIMZIA.
Consider stopping CIMZIA if significant hematologic abnormalities occur.

drug interactions

Do not use CIMZIA in combination with other biological DMARDS.

autoimmunity

Treatment with CIMZIA may result in the formation of autoantibodies and, rarely, in development of a lupus-like syndrome. Discontinue treatment if symptoms of a lupus-like syndrome develop.

immunizations

Patients on CIMZIA should not receive live or live-attenuated vaccines.

adverse reactions

The most common adverse reactions in CIMZIA clinical trials (≥8%) were upper respiratory infections (18%), rash (9%), and urinary tract infections (8%).

Please see full Prescribing Information.

General References

CIMZIA^® [prescribing information], Smyrna, GA: UCB, Inc.; 2019.
Keystone E, van der Heijde D, Mason D Jr, et al. Certolizumab pegol plus methotrexate is significantly more effective than placebo plus methotrexate in active rheumatoid arthritis: findings of a fifty‐two–week, phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Arthritis Rheum. 2008;58:3319-3329.
Schwartzman S, Morgan GJ Jr. Does route of administration affect the outcome of TNF antagonist therapy? Arthritis Res Ther. 2004;6(Suppl 2):S19-S23.
Sheikhzadeh A, Yoon J, Formosa D, et al. The effect of a new syringe design on the ability of rheumatoid arthritis patients to inject a biological medication. Appl Ergon. 2012;43:368-375.
Data on file. UCB, Inc.; Smyrna, GA.

Rheumatology References (including RA, PsA and AS; nr-axSpA references are listed below)

Veronese FM, Mero A. The impact of PEGylation on biologic therapies. Biodrugs. 2008;22:315-329.
Weir N, Athwal D, Brown D, et al. A new generation of high-affinity humanized PEGylated Fab' fragment anti-tumor necrosis factor-alpha monoclonal antibodies. Therapy. 2006;3:535-545.
Chapman AP. PEGylated antibodies and antibody fragments for improved therapy: a review. Adv Drug Deliv Rev. 2002;54:531-545.
Harris JM, Chess RB. Effect of pegylation on pharmaceuticals. Nat Rev Drug Discov. 2003;2:214-221.
Mease PJ, Fleischmann R, Deodhar AA, et al. Effect of certolizumab pegol on signs and symptoms in patients with psoriatic arthritis: 24-week results of a phase 3 double-blind randomised placebo-controlled study (RAPID-PsA). Ann Rheum Dis. 2014;73:48-55.
Landewe R, Braun J, Deodhar A, et al. Efficacy of certolizumab pegol on signs and symptoms of axial spondyloarthritis including ankylosing spondylitis: 24-week results of a double-blind randomised placebo-controlled phase 3 study. Ann Rheum Dis. 2014;73(1):39-47.
Weinblatt ME, Fleischmann R, Huizinga TW, et al. Efficacy and safety of certolizumab pegol in a broad population of patients with active rheumatoid arthritis: results from the REALISTIC phase IIIb study. Rheumatology. 2012;51:2204-2214.
Gladman D, Fleischmann R, Coteur G, Woltering F, Mease PJ. Effect of certolizumab pegol on multiple facets of psoriatic arthritis as reported by patients: 24-week patient-reported outcome results of a phase III, multicenter study. Arthritis Care Res. 2014;66(7):1085-1092.

Gastroenterology References

Schreiber S, Khaliq-Kareemi M, Lawrance IC, et al. Maintenance therapy with certolizumab pegol for Crohn’s disease. N Engl J Med. 2007;357:239-250.
Schreiber S, Colombel JF, Bloomfield R, et al. Increased response and remission rates in short-duration Crohn’s disease with subcutaneous certolizumab pegol: an analysis of PRECiSE 2 randomized maintenance trial data. Am J Gastroenterol. 2010;105(7):1574-1582.
Feagan BG, Coteur G, Tan S, Keininger DL, Schreiber S. Clinically meaningful improvement in health-related quality of life in a randomized controlled trial of certolizumab pegol maintenance therapy for Crohn’s disease. Am J Gastroenterol. 2009;104(8):1976-1983.
Pallis AG, Mouzas IA, Vlachonikolis IG. The inflammatory bowel disease questionnaire: a review of its national validation studies. Inflamm Bowel Dis. 2004;10(3):261-269.

Dermatology References

Gottlieb AB, Blauvelt A, Thaçi D, et al. Certolizumab pegol for the treatment of chronic plaque psoriasis: results through 48 weeks from two phase 3, multicenter, randomized, double-blinded, placebo-controlled studies (CIMPASI-1 and CIMPASI-2). J Am Acad Dermatol. 2018;79(2):302-314.e6.
Lebwohl M, Blauvelt A, Paul C, et al. Certolizumab pegol for the treatment of chronic plaque psoriasis: results through 48 weeks of a phase 3, multicenter, randomized, double-blinded, etanercept- and placebo-controlled study (CIMPACT). J Am Acad Dermatol. 2018;79(2):266-276.e5.
Nesbitt A, Fossati G, Bergin M, et al. Mechanism of action of certolizumab pegol (CDP870): in vitro comparison with other anti-tumor necrosis factor alpha agents. Inflamm Bowel Dis. 2007;13(11):1323-1332.
Pasut G. Pegylation of biological molecules and potential benefits: pharmacological properties of certolizumab pegol. BioDrugs. 2014;28 (suppl 1):S15-S23.
Porter C, Armstrong-Fisher S, Kopotsha T, et al. Certolizumab pegol does not bind the neonatal Fc receptor (FcRn): consequences for FcRn-mediated in vitro transcytosis and ex vivo human placental transfer. J Reprod Immunol. 2016;116:7-12.
Humira [prescribing information]. North Chicago, IL: Abbvie Inc.; 2018.
Enbrel [prescribing information]. Thousand Oaks, CA: Amgen Inc.; 2017.
Remicade [prescribing information]. Horsham, PA: Janssen Biotech, Inc.; 2018.
Stelara [prescribing information]. Horsham, PA: Janssen Biotech, Inc.; 2018.
Cosentyx [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2018.
Taltz [prescribing information]. Indianapolis, IN: Eli Lilly and Company; 2017.
Tremfya [prescribing information]. Horsham, PA: Janssen Biotech, Inc.; 2017.
Siliq [prescribing information]. Bridgewater, NJ: Valeant Pharmaceuticals North America LLC; 2017.
Ilumya [prescribing information]. Whitehouse Station, NJ: Merck & Co., Inc.; 2018.
van der Heijde D, Deodhar A, FitzGerald O, et al. 4-year results from the RAPID-PsA phase 3 randomised placebo-controlled trial of certolizumab pegol in psoriatic arthritis. RMD Open. 2018;4(1):e000582.
Felson DT, Anderson JJ, Boers M, et al. American College of Rheumatology preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheumatol. 1995;38(6)727-735.
Mahadevan U, Wolf DC, Dubinsky M, et al. Placental transfer of anti-tumor necrosis factor agents in pregnant patients with inflammatory bowel disease. Clin Gastroenterol Hepatol. 2013;11(3):286-292.
Mariette X, Förger F, Abraham B, et al. Lack of placental transfer of certolizumab pegol during pregnancy: results from CRIB, a prospective, postmarketing, pharmacokinetic study. Ann Rheum Dis. 2018;77(2):228-233.
Clowse MEB, Förger F, Hwang C, et al. Minimal to no transfer of certolizumab pegol into breast milk: results from CRADLE, a prospective, postmarketing, multicentre, pharmacokinetic study. Ann Rheum Dis. 2017;76(11):1890-1896.

nr-axSpA References

Deodhar A, Gensler LS, Kay J, et al. A 52-week randomized placebo-controlled trial of certolizumab pegol in non-radiographic axial spondyloarthritis. Arthritis Rheumatol. 2019;71(7):1101-1111.
Sieper J, Rudwaleit M, Baraliakos X, et al. The assessment of spondyloarthritis international society (ASAS) handbook: a guide to assess spondyloarthritis. Ann Rheum Dis. 2009;68:ii1-ii44.