Certolizumab Pegol
Cimzia (UCB)
Certolizumab Pegol — Approved Indications
| Indication | Approved Population | Therapy Type | Status |
|---|---|---|---|
| Rheumatoid arthritis — moderate to severe | Adults | Monotherapy or with MTX/DMARDs | FDA Approved |
| Crohn’s disease — moderate to severe | Adults | Monotherapy or adjunctive | FDA Approved |
| Psoriatic arthritis | Adults | With or without non-biologic DMARDs | FDA Approved |
| Ankylosing spondylitis | Adults | Monotherapy | FDA Approved |
| Non-radiographic axial spondyloarthritis (nr-axSpA) | Adults with objective signs of inflammation | Monotherapy | FDA Approved |
| Plaque psoriasis — moderate to severe | Adults | Monotherapy | FDA Approved |
| Polyarticular juvenile idiopathic arthritis (pJIA) | ≥2 years | Monotherapy or with MTX | FDA Approved (2024) |
Certolizumab pegol is the only PEGylated, Fc-free anti-TNF-α agent available for clinical use. Initially approved for Crohn’s disease in 2008, it received its RA indication in 2009 based on the RAPID 1 and RAPID 2 trials. Its Fab’-only structure means it does not induce complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity, or apoptosis of TNF-expressing cells — a mechanistic distinction from whole-antibody TNF inhibitors. This same structural feature results in negligible placental transfer, making certolizumab pegol a preferred anti-TNF option for women of childbearing potential.
Hidradenitis suppurativa — refractory cases where other TNF inhibitors are not suitable. Evidence quality: Low (case series).
Non-infectious uveitis — refractory disease, particularly when pregnancy planning is a consideration. Evidence quality: Low (case reports, expert opinion).
Certolizumab Pegol Dosing by Clinical Scenario
Adult Dosing
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| RA — with or without MTX | 400 mg SC at Weeks 0, 2, 4 | 200 mg SC Q2W | 400 mg Q4W (alternative) | Each 400 mg dose given as 2 × 200 mg injections; MTX not required but reduces immunogenicity 400 mg Q4W is an alternative maintenance regimen |
| Crohn’s disease — adult | 400 mg SC at Weeks 0, 2, 4 | 400 mg SC Q4W | 400 mg Q4W | Higher maintenance dose than RA; no approved dose escalation beyond 400 mg Q4W |
| Psoriatic arthritis | 400 mg SC at Weeks 0, 2, 4 | 200 mg SC Q2W or 400 mg Q4W | 400 mg Q4W | With or without non-biologic DMARDs |
| Ankylosing spondylitis / nr-axSpA | 400 mg SC at Weeks 0, 2, 4 | 200 mg SC Q2W or 400 mg Q4W | 400 mg Q4W | Same dosing for both AS and nr-axSpA |
| Plaque psoriasis — moderate to severe | 400 mg SC at Weeks 0, 2, 4 | 400 mg SC Q2W | 400 mg Q2W | Standard maintenance is 400 mg Q2W; for patients ≤90 kg, 200 mg Q2W may be considered after loading Higher maintenance exposure needed for psoriasis than for RA |
Certolizumab pegol uses the same 400 mg loading regimen (Weeks 0, 2, and 4) for every approved indication, simplifying prescribing. Each 400 mg dose requires two separate 200 mg subcutaneous injections at different sites. The key difference between indications is the maintenance dose: RA uses 200 mg Q2W (or 400 mg Q4W), while Crohn’s disease uses the higher 400 mg Q4W, and psoriasis may require 400 mg Q2W. Unlike infliximab, concomitant MTX is not mandated for the RA indication, though its use reduces immunogenicity (neutralising antibody rate 2% with MTX vs 8% monotherapy; overall antibody-positive rate 7%).
Pharmacology
Mechanism of Action
Certolizumab pegol is a recombinant, humanised antibody Fab’ fragment conjugated to an approximately 40 kDa polyethylene glycol (PEG) moiety, yielding a total molecular weight of ~91 kDa. It binds human TNF-α with high affinity (KD ~90 pM), selectively neutralising both soluble and membrane-bound TNF-α and blocking its interaction with TNFR1 and TNFR2. Because certolizumab pegol lacks the Fc (fragment crystallisable) region present in conventional IgG antibodies, it does not fix complement, does not mediate antibody-dependent cellular cytotoxicity (ADCC), and does not induce apoptosis of TNF-expressing cells in vitro. This Fc-free structure also accounts for its negligible placental transfer — a clinically meaningful distinction from other anti-TNF agents during pregnancy. The PEG moiety extends the circulating half-life of the Fab’ fragment from hours to approximately 14 days, enabling fortnightly or monthly dosing.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | Bioavailability ~80% (76–88%); Tmax 54–171 hours; dose-proportional PK | Slow SC absorption supports Q2W or Q4W dosing; no food effect |
| Distribution | Vss ~6.4 L (pop PK); primarily intravascular | Distribution approximates plasma volume; minimal extravascular penetration typical of PEGylated proteins |
| Metabolism | Fab’ fragment: proteolytic catabolism; PEG moiety: not further metabolised, renally excreted; not CYP-mediated | No conventional CYP drug interactions; however, TNF normalisation may restore suppressed CYP450 activity |
| Elimination | Terminal t½ ~14 days (311 h); clearance ~0.43 L/day in 70 kg patient; anti-CZP antibodies increase clearance 3.6-fold | PEGylation extends half-life from hours (native Fab’) to ~2 weeks; concomitant MTX reduces ADA formation |
Side Effects
Adverse reaction data below are from premarketing controlled clinical trials across all adult indications and placebo-controlled RA studies (FDA PI), unless otherwise stated.
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Upper respiratory infections (nasopharyngitis, laryngitis, viral) | 20% vs 13% placebo | Most common adverse reaction across all indications; generally mild and self-limiting |
| Upper respiratory infections (all populations combined) | 18% (≥8% threshold) | Across all premarketing controlled trials; consistent with the TNF inhibitor class |
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Rash | 9% | Second most common across all populations; evaluate for new psoriasiform eruptions |
| Urinary tract infections | 8% (7% vs 6% in controlled studies) | Includes cystitis and bacteriuria; treat promptly |
| Arthralgia | 6% vs 4% placebo | May be difficult to distinguish from underlying disease; also a feature of delayed hypersensitivity |
| Injection site reactions | ~5% | Generally mild; PEGylation may reduce injection site reactions compared to non-PEGylated biologics |
| Headache | ~5% | Typically mild and transient |
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| Serious infections (pneumonia, cellulitis, pyelonephritis, TB) | 0.06/PY vs 0.02/PY placebo (RA) | Any time during treatment | Discontinue certolizumab; initiate appropriate antimicrobials |
| Tuberculosis | 0.61/100 PY (all indications) | Median 345 days; often disseminated | Screen before and during therapy; treat latent TB before starting; stop for active TB |
| Invasive fungal infections | Rare | Variable; consider in endemic regions | Empiric antifungal therapy in febrile patients from endemic areas; discontinue |
| Hypersensitivity reactions (angioedema, anaphylaxis, serum sickness, urticaria) | Rare | During or after injection | Permanent discontinuation; emergency treatment as needed |
| Lymphoma | ~2-fold higher than general population | Months to years | Evaluate unexplained lymphadenopathy; refer to oncology |
| Hepatosplenic T-cell lymphoma (HSTCL) | Very rare (post-marketing) | Months to years; mainly young IBD patients on thiopurines | Almost universally fatal; weigh risks carefully in young IBD patients on combination therapy |
| Heart failure (new onset or worsening) | Rare (class effect) | Weeks to months | Exercise caution; monitor closely; discontinue if CHF worsens |
| Demyelinating disease | Rare | Weeks to months | Discontinue; refer to neurology |
| Lupus-like syndrome | Rare (autoantibodies in 4% vs 2% placebo) | Months | Discontinue; symptoms typically resolve |
| HBV reactivation | Rare (carriers at risk) | During or after treatment | Screen all patients before initiation; stop and start antiviral if reactivation occurs |
Certolizumab pegol can cause erroneously elevated activated partial thromboplastin time (aPTT) results in patients without true coagulation abnormalities. This has been observed with the PTT-Lupus Anticoagulant test (Diagnostica Stago), HemosIL APTT-SP, and HemosIL lyophilised silica tests (Instrumentation Laboratories). Prothrombin time (PT) and thrombin time (TT) assays are not affected. There is no evidence of an in vivo coagulation effect. Clinicians should be aware of this interference to avoid unnecessary anticoagulation workups or treatment delays.
Drug Interactions
Certolizumab pegol is not metabolised by CYP450 enzymes. As with other TNF inhibitors, normalisation of TNF-α levels can restore suppressed CYP450 enzyme activity, potentially altering the exposure of narrow-therapeutic-index CYP substrates. The most clinically significant interactions are pharmacodynamic and relate to additive immunosuppression.
Monitoring
- TB ScreeningBefore initiation; periodically
RoutineTST or IGRA before starting. Treat latent TB before initiation. Repeat annually for those with ongoing risk factors. TB rate ~0.61/100 PY across all indications; median onset 345 days. - Hepatitis BBefore initiation; during and after therapy in carriers
RoutineScreen all patients (HBsAg, anti-HBc, anti-HBs). Monitor carriers for HBV DNA and LFTs throughout treatment and for several months after stopping. - CBCBaseline; periodically
RoutineMonitor for cytopenias, pancytopenia, and thrombophilia. Check urgently if fever, bruising, or pallor develops. - Signs of InfectionEvery visit
RoutineInfection rate 0.91/PY vs 0.72/PY placebo in RA. Assess for fever, cough, weight loss, night sweats at each encounter. - Skin ExaminationAnnually
RoutineMelanoma and Merkel cell carcinoma reported with TNF blockers. Periodic skin examination, especially with prior skin malignancy risk factors. - aPTT ResultsWhen coagulation studies ordered
Trigger-BasedBe aware of potential false aPTT elevation. No in vivo coagulation effect. Use PT or anti-Xa assays if coagulation assessment needed. - Heart FailureIf pre-existing
Trigger-BasedMonitor for worsening dyspnoea, oedema, weight gain. Exercise caution; discontinue if worsening. - Neurological SymptomsIf new symptoms
Trigger-BasedEvaluate new visual changes, numbness, weakness for demyelinating disease. Discontinue and refer.
Contraindications & Cautions
Absolute Contraindications
- History of serious hypersensitivity reaction to certolizumab pegol or any excipient (reactions have included angioedema, anaphylaxis, serum sickness, urticaria) (FDA PI §4).
Relative Contraindications (Specialist Input Recommended)
- Active serious infection — do not initiate until fully controlled.
- Active or untreated latent TB — complete or initiate latent TB treatment before starting.
- Pre-existing demyelinating disease (MS, optic neuritis).
- Moderate to severe heart failure (NYHA III/IV) — per Canadian labeling; US label advises caution.
- History of malignancy — risk-benefit evaluation required.
Use with Caution
- Mild heart failure (NYHA I/II) — monitor closely.
- Elderly patients (≥65 years) — higher serious infection risk.
- HBV carriers — monitor during and after treatment.
- Renal impairment — PEG component pharmacokinetics may be dependent on renal function; not formally studied.
- Latex-sensitive patients — prefilled syringe needle shield contains a derivative of natural rubber latex.
Serious Infections: Patients treated with certolizumab pegol are at increased risk for developing serious infections leading to hospitalisation or death, including TB, invasive fungal infections, and bacterial, viral, and other opportunistic infections. Discontinue certolizumab pegol if a serious infection or sepsis develops.
Malignancy: Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers. Post-marketing cases of HSTCL have occurred, almost exclusively in young males with IBD receiving concurrent azathioprine or 6-mercaptopurine.
Patient Counselling
Purpose of Therapy
Certolizumab pegol works by blocking a protein called TNF-alpha that drives inflammation in conditions such as rheumatoid arthritis, Crohn’s disease, and psoriasis. By reducing this inflammation, it helps relieve joint pain, stiffness, and swelling, and can slow joint damage. It is unique among TNF blockers because its structure results in minimal transfer across the placenta during pregnancy.
How to Take
Certolizumab pegol is given as an injection under the skin. After initial training, patients can self-inject using a prefilled syringe. The loading doses are given at Weeks 0, 2, and 4 (each dose requires two separate 200 mg injections), followed by a maintenance dose that varies by condition. Injections should be given in the thigh or abdomen, rotating sites each time.
Sources
- UCB, Inc. CIMZIA (certolizumab pegol) for injection, for subcutaneous use. Full Prescribing Information. Revised 2024. FDA LabelPrimary source for all dosing, indications, boxed warnings, adverse reaction incidence rates, and PK data.
- UCB, Inc. CIMZIA (certolizumab pegol) injection. Full Prescribing Information. 2019 revision. FDA Label (2019)Label revision adding nr-axSpA indication with detailed immunogenicity and aPTT interference data.
- 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 (RAPID 1). Arthritis Rheum. 2008;58(11):3319-3329. doi:10.1002/art.23964Pivotal phase III trial demonstrating ACR20 response and inhibition of radiographic progression with certolizumab + MTX in RA.
- Smolen J, Landewé RB, Mease P, et al. Efficacy and safety of certolizumab pegol plus methotrexate in active rheumatoid arthritis: the RAPID 2 study. Ann Rheum Dis. 2009;68(6):797-804. doi:10.1136/ard.2008.101659Second pivotal RA trial confirming rapid and sustained clinical improvement with certolizumab + MTX.
- 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(6):805-811. doi:10.1136/ard.2008.099291Phase III monotherapy trial supporting certolizumab 400 mg Q4W as a monotherapy option in RA.
- Sandborn WJ, Feagan BG, Stoinov S, et al. Certolizumab pegol for the treatment of Crohn’s disease. N Engl J Med. 2007;357(3):228-238. doi:10.1056/NEJMoa067594PRECiSE 1 trial establishing certolizumab efficacy for induction and maintenance of clinical response in Crohn’s disease.
- Fraenkel L, Bathon JM, England BR, et al. 2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Care Res. 2021;73(7):924-939. doi:10.1002/acr.24596Current ACR guideline positioning TNF inhibitors including certolizumab as preferred biologics after csDMARD failure.
- Smolen JS, Landewé RBM, Bijlsma JWJ, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological DMARDs: 2022 update. Ann Rheum Dis. 2023;82(1):3-18. doi:10.1136/ard-2022-223356EULAR consensus on biologic DMARD sequencing and pregnancy considerations in RA management.
- 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. Inflamm Bowel Dis. 2007;13(11):1323-1332. doi:10.1002/ibd.20225Key mechanistic study demonstrating that certolizumab (Fc-free) does not induce CDC, ADCC, or apoptosis unlike whole-antibody TNF blockers.
- Wade JR, Parker G, Kosutic G, et al. Population pharmacokinetic analysis of certolizumab pegol in patients with Crohn’s disease. J Clin Pharmacol. 2015;55(8):866-874. doi:10.1002/jcph.491Pop PK model in 2,157 CD patients identifying BSA, albumin, CRP, and anti-drug antibodies as key covariates for clearance.
- 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. doi:10.1136/annrheumdis-2017-212196Prospective study confirming negligible placental transfer of certolizumab pegol, supporting its use during pregnancy.
- Certolizumab Pegol. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024. NCBI BookshelfPeer-reviewed pharmacology overview covering all approved indications, dosing, and adverse effects.