Cimzia | Pharmacology Mentor

Generic Name

Cimzia

Mechanism

Cimzia (*adalimumab*) is a fully human IgG1 κ monoclonal antibody that selectively binds soluble and membrane‑bound tumor necrosis factor‑α (TNF‑α), neutralizing its pro‑inflammatory effects.
• Inhibition of TNF‑α blocks its interaction with TNFR1/TNFR2, reducing NF‑κB activation and subsequent cytokine release (IL‑1, IL‑6, IFN‑γ).
• This leads to attenuation of immune cell infiltration, decreased synovial inflammation, and improved mucosal healing in inflammatory bowel diseases.
• Because of its IgG1 isotype, it also mediates antibody‑dependent cellular cytotoxicity (ADCC) against TNF‑α‑expressing cells.

Pharmacokinetics

Absorption: Subcutaneous (SC) injection; ~70 % bioavailability.
Distribution: Volume of distribution ≈ 4 L; extensive binding to plasma proteins (≈ 98 %).
Metabolism: Proteolytic catabolism; no clinically relevant cytochrome P450 interactions.
Elimination: Half‑life ≈ 2 weeks (12–15 days) at steady state; dosing interval 2 weeks (some indications allow 4 weeks).
Special populations: No dose adjustment needed for renal or hepatic impairment; caution in HIV‑positive patients due to immunosuppression.

Indications

Rheumatoid arthritis (RA) – active disease, inadequate response to methotrexate or other disease‑modifying agents.
Psoriatic arthritis (PsA) – active peripheral arthritis or enthesitis.
Ankylosing spondylitis (AS) – active disease.
Plaque psoriasis – moderate‑to‑severe disease (oral/SC).
Crohn’s disease (CD) and Ulcerative colitis (UC) – moderate‑to‑severe disease refractory to conventional therapy.

Contraindications

Active infections (TB, hepatitis, HBV, fungal).
Known hypersensitivity to adalimumab or other components.
Severe heart failure (NYHA III‑IV).
Mental health: risk of mood changes, depression, suicidality.
Vaccination: live vaccines contraindicated; patient should be immunized pre‑treatment.

> Warning: Increased risk of serious infections, malignancy (especially lymphoma, skin cancers), and demyelinating disorders. Use of concurrent corticosteroids or other biologics raises infection risk.

Dosing

Disease	Initial Dose	Maintenance Dose	Administration
RA, PsA, AS	80 mg SC (week 0)	40 mg SC every 2 weeks	Subcutaneous injection (left arm, abdomen, thigh)
Crohn’s / UC	80 mg SC (weeks 0, 2)	40 mg SC every 2 weeks	SC
Plaque psoriasis	80 mg SC (weeks 0, 2)	40 mg SC every 2 weeks	SC
Maintenance flexibility	40 mg SC every 4 weeks (for some conditions)	–	–

• Use pre‑filled syringe or autoinjector (Amplyra®).
• Rotate injection sites to minimize lipoatrophy.

Adverse Effects

Common (≥ 5 %):
• Injection‑site reactions (pain, erythema, induration)
• Upper respiratory tract infections
• Headache
• Nausea

Serious (≥ 1 %):
• Serious infections (severe bacterial, TB re‑activation, fungal)
• Malignancies (non‑melanoma skin cancers, lymphoma)
• Demyelinating disorders (multiple sclerosis, optic neuritis)
• Heart failure exacerbation

Rare (< 1 %):
• Cytokine‑release syndrome
• Severe hypersensitivity (anaphylaxis)
• Autoimmune hemolytic anemia
• Vasculitis

Monitoring

Baseline: CBC with differential, LFTs, renal function, hepatitis B/C serology, TB screening (IGRA or TST).
During therapy:
CBC and LFTs every 3 months (or as clinically indicated).
Monitor for signs of infection; consider screening for TB annually.
For patients with high malignancy risk, skin examinations every 6 months.
Vaccinations: Ensure non‑live vaccines (influenza, pneumococcal, COVID‑19 mRNA) are administered at least 2 weeks before starting therapy.

Clinical Pearls

Dual‑track dosing flexibility: The 40 mg every 4 weeks option can improve adherence without compromising efficacy in RA, PsA, and CD once disease control is achieved.
Switching strategies: If inadequate response to adalimumab, a short washout period (≈ 4 weeks) followed by switch to another TNF‑α inhibitor (e.g., infliximab) is often effective; stasis may occur if switching within 2 weeks.
Hydrocontact: Avoid simultaneous use of non‑steroidal anti‑inflammatory drugs (NSAIDs) and adalimumab due to synergistic risk of GI ulceration and infection.
Pregnancy considerations: Classified as Category B; safe data in observational registries, but avoid live vaccines and influenza vaccine timing.
Pediatric dosing: Weight‑based (≤ 20 mg/kg) for RA and ≥ 30 mg/kg for JIA at maintenance; consult pediatric specialist for CD/UC.

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• *For detailed prescribing information, consult the labeled product monograph or the FDA’s drug approval documents.*