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Certolizumab Pegol

Class: Disease-modifying Antirheumatic Drugs
Molecular Formula: C2115H3252N556O673S16
CAS Number: 428863-50-7
Brands: Cimzia

Warning(s)

  • Serious Infections
  • Increased risk of serious infections involving various organ systems and sites that may require hospitalization or result in death; tuberculosis (frequently disseminated or extrapulmonary), invasive fungal infections (may be disseminated), bacterial (e.g., legionellosis, listeriosis) and viral infections, and other opportunistic infections reported.1 6 24 (See Infectious Complications under Cautions.)

  • Carefully consider risks and benefits prior to initiating certolizumab pegol therapy in patients with chronic or recurring infections.1 24

  • Evaluate patients for latent tuberculosis infection prior to and periodically during certolizumab pegol therapy; if indicated, initiate appropriate antimycobacterial regimen prior to initiating therapy.1 24

  • Closely monitor patients for infection, including active tuberculosis in those with a negative tuberculin skin test, during and after treatment.1 6 24 Discontinue certolizumab pegol if serious infection occurs.1 6 Consider empiric antifungal therapy if serious systemic illness occurs in a patient at risk for invasive fungal infections.1 6 24

  • Malignancy
  • Lymphoma and other malignancies (some fatal) reported in children and adolescents receiving TNF blocking agents.1 9 25 (See Malignancies and Lymphoproliferative Disorders under Cautions.)

Introduction

Biologic response modifier and disease-modifying antirheumatic drug (DMARD); a recombinant humanized Fab′ fragment of a monoclonal antibody specific for tumor necrosis factor (TNF; TNF-α).1 2 3 7 8 14 15 16

Uses for Certolizumab Pegol

Crohn’s Disease

Used to reduce the signs and symptoms of moderately to severely active Crohn’s disease and to maintain clinical response in adults who have had an inadequate response to conventional therapies.1 2 3

Slideshow: Drug Treatment for Rheumatoid Arthritis - What Are Your Options?

Rheumatoid Arthritis

Management of moderately to severely active rheumatoid arthritis in adults.1 May be used alone or in combination with methotrexate or other nonbiologic DMARDs.1

Ankylosing Spondylitis

Management of active ankylosing spondylitis in adults.1 31

Psoriatic Arthritis

Management of active psoriatic arthritis in adults.1 32 33

Certolizumab Pegol Dosage and Administration

General

Concomitant Therapy

  • May be used alone or in combination with methotrexate or other nonbiologic DMARDs; concomitant use with biologic DMARDs, including other TNF blocking agents, not recommended.1

  • Corticosteroids, NSAIAs, and/or analgesics may be continued in adults with rheumatoid arthritis, ankylosing spondylitis, or psoriatic arthritis.1 17 18 19 31 32

  • Administered concomitantly with aminosalicylates, corticosteroids, azathioprine, mercaptopurine, methotrexate, or anti-infective agents in patients with Crohn’s disease.2 3 (See Malignancies and Lymphoproliferative Disorders under Cautions.)

Administration

Sub-Q Administration

Administer by sub-Q injection into the thighs or abdomen using a 23-gauge needle.1 Rotate injection sites.1 Do not inject into areas where the skin is tender, bruised, red, or hard.1

Allow reconstituted solution and prefilled syringes sit at room temperature for 30 minutes prior to administration.1

Following reconstitution, draw up each 400-mg dose into 2 syringes, each containing 200 mg, and administer by sub-Q injection into separate sites on the thighs or abdomen using 23-gauge needles.1

Reconstituted solution intended for use under the guidance and supervision of a clinician.1 Certolizumab pegol solution supplied in prefilled syringes may be self-administered if the clinician determines that the patient and/or their caregiver is competent to safely administer the drug after appropriate training.1

Reconstitution

Allow lyophilized powder kit (containing drug, diluent, syringes, needles) to reach room temperature prior to reconstitution.1

Reconstitute vial containing 200 mg of certolizumab pegol lyophilized powder by adding 1 mL of sterile water for injection (provided by manufacturer) to provide a solution containing approximately 200 mg/mL.1

Gently swirl vial to ensure all of the powder comes into contact with the diluent; do not shake.1 Leave vial undisturbed to fully reconstitute (may take up to 30 minutes).1

Dosage

Adults

Crohn’s Disease
Sub-Q

400 mg (as two 200-mg injections at separate sites) at 0, 2, and 4 weeks (induction regimen); patients who respond may receive additional 400-mg doses every 4 weeks (maintenance regimen).1

Rheumatoid Arthritis
Sub-Q

400 mg (as two 200-mg injections at separate sites) at 0, 2, and 4 weeks, followed by 200 mg every 2 weeks.1 For maintenance therapy, 400 mg every 4 weeks may be considered.1

Ankylosing Spondylitis
Sub-Q

400 mg (as two 200-mg injections at separate sites) at 0, 2, and 4 weeks, followed by 200 mg every 2 weeks or 400 mg every 4 weeks.1

Psoriatic Arthritis
Sub-Q

400 mg (as two 200-mg injections at separate sites) at 0, 2, and 4 weeks, followed by 200 mg every 2 weeks.1 For maintenance therapy, 400 mg every 4 weeks may be considered.1

Special Populations

Dosage adjustment based on weight not necessary.1 (See Special Populations under Pharmacokinetics.)

Hepatic Impairment

No specific dosage recommendations at this time.1

Renal Impairment

Insufficient data available to provide dosage recommendations for patients with moderate or severe renal impairment.1 (See Special Populations under Pharmacokinetics.)

Geriatric Patients

No specific dosage recommendations at this time.1

Cautions for Certolizumab Pegol

Contraindications

  • Manufacturer states none known.1

Warnings/Precautions

Warnings

Infectious Complications

Increased risk of serious infections involving various organ systems and sites that may require hospitalization or result in death.1 24 Opportunistic infections caused by bacterial, mycobacterial, invasive fungal, viral, parasitic, or other opportunistic pathogens (e.g., aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, histoplasmosis, legionellosis, listeriosis, pneumocystosis, tuberculosis) reported, particularly in patients receiving concomitant therapy with immunosuppressive agents (e.g., methotrexate, corticosteroids).1 2 3 6 24 Infections frequently are disseminated.1 (See Boxed Warning.)

Increased incidence of serious infections observed with concomitant use of a TNF blocking agent and anakinra or abatacept.1 5 23 (See Specific Drugs and Laboratory Tests under Interactions.)

Patients >65 years of age, with comorbid conditions, and/or receiving concomitant therapy with immunosuppressive agents (e.g., corticosteroids, methotrexate) may be at increased risk of infection.1 24

Do not initiate certolizumab pegol in patients with active infections, including clinically important localized infections.1 Consider potential risks and benefits of the drug prior to initiating therapy in patients with a history of chronic, recurring, or opportunistic infections; patients with underlying conditions that may predispose them to infections; and patients who have been exposed to tuberculosis or who have resided or traveled in regions where tuberculosis or mycoses such as histoplasmosis, coccidioidomycosis, or blastomycosis are endemic.1 24

Closely monitor patients during and after treatment for signs or symptoms of infection (e.g., fever, malaise, weight loss, sweats, cough, dyspnea, pulmonary infiltrates, serious systemic illness including shock).1 6 24

If new infection occurs during therapy, perform thorough diagnostic evaluation (appropriate for immunocompromised patient), initiate appropriate anti-infective therapy, and closely monitor patient.1 6 Discontinue certolizumab pegol if serious infection or sepsis develops.1 6

Evaluate all patients for active or latent tuberculosis and for risk factors for tuberculosis prior to and periodically during therapy.1 24 When indicated, initiate appropriate antimycobacterial regimen for treatment of latent tuberculosis infection prior to certolizumab pegol therapy.1 Consider antimycobacterial therapy prior to initiating certolizumab pegol in patients with a history of latent or active tuberculosis for whom adequate antimycobacterial treatment is unconfirmed, and in patients with a negative tuberculin skin test who have risk factors for tuberculosis.1 Consultation with a tuberculosis specialist is recommended when deciding whether to initiate antimycobacterial therapy.1

Monitor all patients, including those with negative tuberculin skin tests, for active tuberculosis.1 Strongly consider tuberculosis in patients who develop new infections during therapy, especially if they previously have traveled to countries where tuberculosis is highly prevalent or have been in close contact with an individual with active tuberculosis.1

Failure to recognize invasive fungal infections has led to delays in appropriate treatment.6 Consider empiric antifungal therapy in patients at risk for invasive fungal infections who develop severe systemic illness.1 6 24 Whenever feasible, consult specialist in fungal infections when making decisions regarding initiation and duration of antifungal therapy.1 6

When deciding whether to reinitiate TNF blocking agent therapy following resolution of an invasive fungal infection, reevaluate risks and benefits, particularly in patients who reside in regions where mycoses are endemic.6 Whenever feasible, consult specialist in fungal infections.6

Malignancies and Lymphoproliferative Disorders

Lymphoma and other malignancies (some fatal) reported during postmarketing surveillance in children and adolescents receiving TNF blocking agents, particularly in those receiving other immunosuppressive agents (e.g., azathioprine, methotrexate) concomitantly.1 9 Malignancies included lymphomas (about 50% of the cases) (e.g., Hodgkin’s disease, non-Hodgkin’s lymphoma) and various other malignancies (e.g., leukemia, melanoma, solid organ cancers), including rare malignancies usually associated with immunosuppression and malignancies not usually observed in children and adolescents (e.g., leiomyosarcoma, hepatic malignancies, renal cell carcinoma).1 9 Median time to occurrence was 30 months (range: 1–84 months) after the initial TNF blocking agent dose.1 FDA has concluded that there is an increased risk of malignancy with TNF blocking agents in children and adolescents; however, the strength of the association is not fully characterized.9

Hepatosplenic T-cell lymphoma (a rare, aggressive, usually fatal T-cell lymphoma) reported mainly in adolescents and young adults with Crohn’s disease or ulcerative colitis receiving TNF blocking agents and/or thiopurine analogs (mercaptopurine or azathioprine).1 25 Most of the patients received a combination of immunosuppressive agents, including TNF blocking agents and thiopurine analogs.1 25

In controlled studies, lymphoma was reported more frequently in patients receiving certolizumab pegol or other TNF blocking agents than in control patients.1 Patients with Crohn’s disease, rheumatoid arthritis, and other chronic inflammatory diseases, especially those with highly active disease and/or chronic exposure to immunosuppressive therapies, may be at increased risk of lymphoma;1 9 25 may be difficult to measure added risk of TNF-blocking agents, azathioprine, and/or mercaptopurine.1 25

In clinical studies of certolizumab pegol, rate of malignancies other than nonmelanoma skin cancer was 0.5 or 0.6 per 100 patient-years in patients receiving certolizumab pegol or placebo, respectively; however, the role of certolizumab pegol use in the development of malignancies not fully determined.1 9

Acute and chronic leukemias (some fatal) reported during postmarketing surveillance of TNF blocking agents in adults and pediatric patients, particularly in those receiving other immunosuppressive agents concomitantly.1 9 Leukemia (most commonly acute myeloid leukemia, chronic lymphocytic leukemia, and chronic myeloid leukemia) generally occurred during first 2 years of therapy.9 FDA has concluded that there is a possible association between TNF blocking agents and development of leukemia; interpretation of findings is complicated because patients with rheumatoid arthritis may be at increased risk for leukemia independent of any treatment with TNF blocking agents.1 9

In controlled studies of other TNF blocking agents in adults at increased risk of malignancies (e.g., patients with COPD and a history of heavy smoking, patients with Wegener’s granulomatosis receiving concomitant cyclophosphamide), a greater proportion of malignancies occurred in patients receiving the TNF blocking agent compared with control patients.28 29

Consider possibility of and monitor for occurrence of malignancies during and following treatment with TNF blocking agents.9 25

Carefully consider risks and benefits of TNF blocking agents, especially in adolescents and young adults and especially in the treatment of Crohn’s disease or ulcerative colitis.1 25

Periodic dermatologic evaluations recommended for all patients, particularly those with risk factors for skin cancer.1

Other Warnings/Precautions

Cardiovascular Effects

Worsening CHF and new-onset CHF reported in patients receiving TNF blocking agents; certolizumab pegol not studied in patients with CHF.1 If used in patients with CHF, caution and careful monitoring recommended.1

Sensitivity Reactions

Angioedema, dyspnea, hypotension, rash, serum sickness, and urticaria reported rarely, sometimes after the first dose.1 If allergic reaction occur, discontinue certolizumab pegol and initiate appropriate treatment.1

HBV Reactivation

Increased risk of reactivation of HBV infection in patients who are chronic carriers of this virus (i.e., hepatitis B surface antigen-positive [HBsAg-positive]).1 5 Fatalities reported.1 Use of multiple immunosuppressive agents may contribute to HBV reactivation.1

Screen all patients for HBV infection prior to initiation of therapy.1 Consultation with an HBV infection specialist is recommended for those who test positive.1

Evaluate and monitor HBV carriers before, during, and for up to several months after therapy.1 Safety and efficacy of antiviral therapy for prevention of HBV reactivation not established.1 Discontinue certolizumab pegol and initiate appropriate treatment (e.g., antiviral therapy) if HBV reactivation occurs.1 Not known whether certolizumab pegol can be readministered once control of a reactivated HBV infection is achieved; caution advised in this situation.1

Nervous System Effects

New onset or exacerbation of central or peripheral nervous system demyelinating disorders (e.g., multiple sclerosis, Guillain-Barré syndrome) reported rarely.1 Exercise caution when considering certolizumab pegol therapy in patients with preexisting or recent-onset central or peripheral nervous system demyelinating disorders.1

Seizure disorder, optic neuritis, and peripheral neuropathy reported rarely.1

Hematologic Effects

Pancytopenia (including aplastic anemia),1 leukopenia, and thrombocytopenia reported rarely; causal relationship unclear.1 Use with caution in patients with a history of substantial hematologic abnormalities.1 Consider discontinuing therapy if substantial hematologic abnormalities occur.1

Immunologic Reactions and Antibody Formation

Possible formation of autoimmune antibodies.1 2 3 Lupus-like syndrome reported rarely.1 Discontinue therapy if manifestations suggestive of a lupus-like syndrome occur.1

Antibodies to certolizumab pegol may develop.1 Incidence of antibody formation was lower in patients receiving concomitant therapy with other immunosuppressive agents (e.g., methotrexate) than in those not receiving immunosuppressive agents at baseline.1

Antibody formation associated with lower plasma drug concentrations and reduced efficacy in patients with rheumatoid arthritis.1 In patients with Crohn’s disease, no apparent association between antibody development and efficacy or adverse events.1

Immunization

Avoid live vaccines.1 (See Interactions.)

Immunosuppression

Safety and efficacy in immunosuppressed patients not evaluated.1

Psoriasis

New-onset psoriasis, including pustular and palmoplantar psoriasis, and exacerbation of existing psoriasis reported with TNF blocking agents, including certolizumab pegol.1 9 Most patients experienced improvement following discontinuance of the TNF blocking agent.9

Consider possibility of and monitor for manifestations (e.g., new rash) of new or worsening psoriasis, particularly pustular and palmoplantar psoriasis.9

Specific Populations

Pregnancy

Category B.1

Pregnancy registry at 877-311-8972 (for patients or clinicians).1

Lactation

Not known whether distributed into milk.1 Discontinue nursing or the drug.1

Pediatric Use

Safety and efficacy not established.1

Malignancies, some fatal, reported in children and adolescents who received TNF-blocking agents.1 9 (See Malignancies and Lymphoproliferative Disorders under Cautions.)

Neonates and infants exposed to certolizumab pegol in utero may have impaired immune responses.1 Low certolizumab pegol concentrations reported in infants exposed to the drug in utero; clinical importance is unknown.1 The drug may be eliminated more slowly in infants than in adults.1 Consider risks and benefits of administering live vaccines to infants exposed to certolizumab pegol in utero; safety of live vaccines in these infants is unknown.1

Geriatric Use

No substantial differences in response relative to younger adults.1

Possible increased incidence of infections in geriatric patients; use with caution.1

Common Adverse Effects

Upper respiratory infection, urinary tract infection, arthralgia, rash.1 2

Interactions for Certolizumab Pegol

No formal drug interaction studies with oral corticosteroids, NSAIAs, analgesics, or immunosuppressants to date.1

Administered concomitantly with methotrexate or other nonbiologic DMARDs, corticosteroids, NSAIAs, and/or other analgesics in patients with rheumatoid arthritis, ankylosing spondylitis, or psoriatic arthritis.1 17 18 19 31 32

Administered concomitantly with aminosalicylates, corticosteroids, azathioprine, mercaptopurine, methotrexate, or anti-infective agents in patients with Crohn’s disease.2 3

Biologic Antirheumatic Agents

Concomitant use of certolizumab pegol and other biologic DMARDs not recommended.1

Use caution when switching from one biologic DMARD to another, since overlapping biologic activity may further increase the risk of infection.29

Vaccines

Avoid live vaccines.1 (See also Pediatric Use under Cautions.) No data available on secondary transmission of infection by live vaccines in certolizumab pegol-treated patients.1

Specific Drugs and Laboratory Tests

Drug

Interaction

Comments

Abatacept

Increased incidence of infection and serious infection, without additional clinical benefit, reported with abatacept and TNF blocking agents in rheumatoid arthritis1 23

Concomitant use not recommended1 23

Use caution when switching from one biologic DMARD to another, since overlapping biologic activity may further increase risk of infection29

Anakinra

Increased incidence of serious infections and neutropenia, without additional clinical benefit, reported with anakinra and etanercept (another TNF blocking agent) in rheumatoid arthritis; similar toxicities expected with certolizumab pegol and anakinra1 5

Concomitant use not recommended1

Use caution when switching from one biologic DMARD to another, since overlapping biologic activity may further increase risk of infection29

Corticosteroids, oral

Increased risk of serious infection1

Used concomitantly in clinical studies1

Influenza virus vaccine

Certolizumab pegol did not suppress immune response to concurrently administered influenza virus vaccine in patients with rheumatoid arthritis; concomitant methotrexate may reduce immune response to the vaccine, but clinical importance unknown 1

Methotrexate

Increased risk of serious infection1

Possible decrease in rate of development of antibodies to certolizumab pegol in patients with rheumatoid arthritis; may result in sustained therapeutic plasma certolizumab pegol concentrations1

Concomitant use with certolizumab pegol may reduce immune response to influenza virus vaccine or pneumococcal polysaccharide vaccine, but clinical importance unknown1

Methotrexate pharmacokinetics not altered by certolizumab pegol in patients with rheumatoid arthritis; effect of methotrexate on certolizumab pharmacokinetics not determined1

Used concomitantly in clinical studies1

Natalizumab

Increased risk of progressive multifocal leukoencephalopathy (PML) or other serious infections1 12

Avoid concomitant use1 12

Pneumococcal polysaccharide vaccine

Certolizumab pegol did not suppress immune response to concurrently administered pneumococcal polysaccharide vaccine in patients with rheumatoid arthritis; concomitant methotrexate may reduce immune response to the vaccine in patients with rheumatoid arthritis, but clinical importance unknown 1

Rituximab

Increased risk of serious infection reported in patients who received rituximab and subsequently received a TNF blocking agent1 13

Concomitant use not recommended1

Use caution when switching from one biologic DMARD to another, since overlapping biologic activity may further increase risk of infection29

Tests, coagulation

May erroneously elevate aPPT; thrombin time and PT unaffected; no evidence of effect on in vivo coagulation1

Tocilizumab

Concomitant use not studied; possibility of increased immunosuppression and increased risk of infection26

Avoid concomitant use26

Use caution when switching from one biologic DMARD to another, since overlapping biologic activity may further increase risk of infection29

Certolizumab Pegol Pharmacokinetics

Absorption

Bioavailability

Bioavailability is approximately 80% following sub-Q administration.1 Peak serum concentrations achieved in 54–171 hours.1

Distribution

Extent

Crosses the placenta in small amounts.1

Elimination

Metabolism

Not studied.1

Elimination Route

Not studied.1 Polyethylene glycol moiety excreted principally in urine.1

Half-life

Approximately 14 days.1

Special Populations

Pharmacokinetics of certolizumab pegol not formally studied in patients with renal impairment.1 However, pharmacokinetics of polyethylene glycol moiety dependent on renal function.1

Among adults, age does not appear to influence pharmacokinetics.1

Clearance of certolizumab pegol is higher with increasing body weight; however, no clinically important weight-related differences observed.1

In patients with certolizumab pegol antibodies, clearance of certolizumab is higher.1

No gender-related pharmacokinetic differences apparent.1

Stability

Storage

Sub-Q

Injection in Prefilled Syringes

2–8°C.1 Do not freeze.1 Protect from light; store in original carton until administration.1

Powder for Injection Kit

2–8°C.1 Do not freeze.1 Protect from light; store in original carton until administration.1

Store reconstituted solution for up to 2 hours at room temperature or up to 24 hours (in vials) at 2–8°C.1 Do not freeze.1

Actions

  • Recombinant humanized Fab′ fragment of an anti-TNF monoclonal antibody conjugated to an approximately 40-kilodalton polyethylene glycol (PEG2MAL40K) in order to prolong the half-life.1 2 3 7 8

  • Binds with high affinity to TNF-α, a cytokine involved in the regulation of immune response.1 2 3 7 8

  • Does not contain a fragment crystallizable (Fc) region or induce complement activation, antibody-dependent cellular cytotoxicity, apoptosis, or neutrophil degranulation in vitro.1 2 3 7 8

Advice to Patients

  • Importance of advising patients about potential benefits and risks of certolizumab pegol.1 9 24 25 Importance of patients reading the manufacturer’s patient information (medication guide) prior to initiation of therapy and before each injection of the drug.1 24 25

  • Importance of instructing patient and/or caregiver regarding proper dosage and administration of certolizumab pegol, including the use of aseptic technique, and proper disposal of needles and syringes if it is determined that the patient and/or caregiver is competent to safely administer the drug.1

  • Increased susceptibility to infection.1 Importance of informing clinicians promptly if any signs or symptoms suggestive of infection (e.g., persistent fever, sweating, cough, dyspnea, fatigue) occur.1 6

  • Risk of lymphoma, including hepatosplenic T-cell lymphoma, leukemia, and other malignancies with use of TNF blocking agents.1 9 25 Importance of informing patients and caregivers about the increased risk of cancer development in children, adolescents, and young adults, taking into account the clinical utility of TNF blocking agents, the relative risks and benefits of these and other immunosuppressive drugs, and the risks associated with untreated disease.9 25 Importance of promptly informing clinicians if signs and symptoms of malignancies (e.g., unexplained weight loss; fatigue; abdominal pain; persistent fever; night sweats; easy bruising or bleeding; swollen lymph nodes in the neck, underarm, or groin; hepatomegaly or splenomegaly) occur.9 25

  • Importance of informing clinician of any new or worsening medical conditions (e.g., heart failure, neurologic disease [e.g., demyelinating disorders], autoimmune disorders [e.g., lupus-like syndrome], cytopenias, psoriasis).1 9

  • Importance of promptly contacting a clinician if manifestations of an allergic reaction (e.g., urticaria, facial swelling, difficulty breathing) occur.1

  • Importance of taking the drug as prescribed and of not altering or discontinuing therapy without first consulting with a clinician.9 25

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses or any history of cancer, tuberculosis, HBV infection, or other chronic or recurrent infections.1 6 24

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Certolizumab Pegol

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for subcutaneous use

2 vials (200 mg each)

Cimzia (available as kit with sterile water for injection diluent, needles, syringes, and alcohol swabs)

UCB

Injection, for subcutaneous use

2 syringes (200 mg/1 mL each)

Cimzia (available as disposable prefilled syringes)

UCB

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions June 11, 2014. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. UCB, Inc. Cimzia (certolizumab pegol) subcutaneous injection and for subcutaneous injection prescribing information. Smyrna, GA; 2013 Oct.

2. Sandborn WJ, Feagan BG, Stoinov S et al. Certolizumab pegol for the treatment of Crohn’s disease. N Engl J Med. 2007; 357:228-38. [PubMed 17634458]

3. Schreiber S, Khaliq-Kareemi M, Lawrance IC et al. Maintenance therapy with certolizumab pegol for Crohn’s disease. N Engl J Med. 2007; 357:239-50. [PubMed 17634459]

4. Best WR, Becktel JM, Singleton JW et al. Development of a Crohn’s disease activity index. National Cooperative Crohn’s Disease Study. Gastroenterology. 1976; 70:439-44. [PubMed 1248701]

5. Amgen/Wyeth Corporation. Enbrel (etanercept) for subcutaneous injection prescribing information. Thousand Oaks, CA: 2008 Jun.

6. Food and Drug Administration, Center for Drug Evaluation and Research. FDA alert: Information for healthcare professionals Cimzia (certolizumab pegol), Enbrel (etanercept), Humira (adalimumab), and Remicade (infliximab). Rockville MD: Food and Drug Administration; 2008 Sep 4. Available from FDA website. Accessed 2008 Sep 25.

7. Bourne T, Fossati G, Nesbitt A. A PEGylated Fab’ fragment against tumor necrosis factor for the treatment of Crohn disease: exploring a new mechanism of action. BioDrug. 2008; 22:331-7.

8. Nesbitt A, Fossati G, Bergin M et al. Mechanism of action of certolizumab pegol (CDP870): in vitro comparison with other anti-tumor necrosis factor α agents. In flamm Bowel Dis. 2007; 13:1323-32.

9. Food and Drug Administration, Center for Drug Evaluation and Research. Information for healthcare professionals: Tumor necrosis factor (TNF) blockers (marketed as Remicade, Enbrel, Humira, Cimzia, and Simponi). FDA alert, Rockville, MD; 2009 Aug 4. Available from FDA website. Accessed 2009 Nov 3.

10. UCB, Smyrna, GA: Personal communication.

11. Cimzia (certolizumab pegol) risk evaluation and mitigation strategy (REMS). From FDA website. Accessed 2010 Jul 28.

12. Biogen Idec Inc. Tysabri (natalizumab) injection prescribing information. Cambridge, MA; 2011 Sep.

13. Janssen Biotech Inc. Simponi (golimumab) injection prescribing information. Horsham, PA; 2011 Sep.

14. Sebba A. Tocilizumab: the first interleukin-6-receptor inhibitor. Am J Health Syst Pharm. 2008; 65:1413-8. [PubMed 18653811]

15. McCluggage LK, Scholtz JM. Golimumab: a tumor necrosis factor alpha inhibitor for the treatment of rheumatoid arthritis. Ann Pharmacother. 2010; 44:135-44. [PubMed 20118145]

16. . Drugs for rheumatoid arthritis. Treat Guidel Med Lett. 2009; 7:37-46; quiz 47-8. [PubMed 19390497]

17. Keystone E, Heijde D, Mason D 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; 58:3319-29. [PubMed 18975346]

18. Smolen J, Landewé RB, Mease P et al. Efficacy and safety of certolizumab pegol plus methotrexate in active rheumatoid arthritis: the RAPID 2 study. A randomised controlled trial. Ann Rheum Dis. 2009; 68:797-804. [PubMed 19015207]

19. Fleischmann R, Vencovsky J, van Vollenhoven RF et al. Efficacy and safety of certolizumab pegol monotherapy every 4 weeks in patients with rheumatoid arthritis failing previous disease-modifying antirheumatic therapy: the FAST4WARD study. Ann Rheum Dis. 2009; 68:805-11. [PubMed 19015206]

20. Felson DT, Anderson JJ, Boers M et al. American College of Rheumatology preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum. 1995; 38:727-35. [PubMed 7779114]

21. Felson DT, Anderson JJ, Boers M et al. The American College of Rheumatology preliminary core set of disease activity measures for rheumatoid arthritis clinical trials. Arthritis Rheum. 1993; 36:729-40. [PubMed 8507213]

22. Felson DT, Anderson JJ, Lange MLM et al. Should improvement in rheumatoid arthritis clinical trials be defined as fifty percent or seventy percent improvement in core set measures, rather than twenty percent. Arthritis Rheum. 1998; 41:1564-70. [IDIS 411264] [PubMed 9751088]

23. Bristol-Myers Squibb. Orencia (abatacept) lyophilized powder for intravenous infusion prescribing information. Princeton, NJ; 2011 Sep.

24. US Food and Drug Administration. FDA drug safety communication: Drug labels for the tumor necrosis factor-alpha (TNFα) blockers now include warnings about infection with Legionella and Listeria bacteria. Rockville, MD; 2011 Sep 7. From FDA website. Accessed 2011 Oct 2.

25. US Food and Drug Administration. FDA drug safety communication: Safety review update on reports of hepatosplenic T-cell lymphoma in adolescents and young adults receiving tumor necrosis factor (TNF) blockers, azathioprine and/or mercaptopurine. Rockville, MD; 2011 Apr 14. From FDA website. Accessed 2011 Jul 26.

26. Genentech. Actemra (tocilizumab) injection prescribing information. South San Francisco, CA; 2011 Apr.

27. Genentech. Rituxan (rituximab) injection prescribing information. South San Francisco, CA; 2011 Apr.

28. Amgen/Pfizer. Enbrel (etanercept) prescribing information. Thousand Oaks, CA; 2011 Sep.

29. Janssen Biotech, Inc. Remicade (infliximab) for IV injection prescribing information. Horsham, PA; 2011 Sep.

30. 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 Suppl 2:ii1-44. [PubMed 19433414]

31. Landewé 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; 73:39-47. [PubMed 24013647]

32. 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. [PubMed 23942868]

33. van der Heijde D, Fleischmann R, Wollenhaupt J et al. Effect of different imputation approaches on the evaluation of radiographic progression in patients with psoriatic arthritis: results of the RAPID-PsA 24-week phase III double-blind randomised placebo-controlled study of certolizumab pegol. Ann Rheum Dis. 2014; 73:233-7. [PubMed 23942869]

34. Smolen JS, Kay J, Doyle MK et al. Golimumab in patients with active rheumatoid arthritis after treatment with tumour necrosis factor alpha inhibitors (GO-AFTER study): a multicentre, randomised, double-blind, placebo-controlled, phase III trial. Lancet. 2009; 374:210-21. [PubMed 19560810]

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