RA - Biologic Drugs

Question 1

Anti-TNF Therapeutics

Answer 1

• Etanercept (Enbrel)
• Infliximab (Remicade)
• Adalimumab (Humira)
• Golimumab (Simponi)
• Certolizumab Pegol (Cimzia)

Question 2

Anti-TNF MoA, Warnings, Administration, Monitoring

Answer 2

• MoA: block the inflammatory effects of TNF
• Warnings: Serious infections, Malignancy
• All injections
• Monitoring: Initial TB test, HBV/HIV screening, monitor for infection

Question 3

Etanercept

Answer 3

• Enbrel
• “-cept” = receptor fusion protien
• Biosimilar to Erelzi
• Dose: 25 mg SC twice weekly or 50 mg qweek
• Indications: RA, plaque psoriasis, psoriatic arthritis
• Consists of 2 soluble TNF receptor moieties linked to Fc portion of IgG (decoy receptor)
• Onset: 1-2 weeks
• Half life: 7-12 days
• Risk X combos: other immunosuppressives, live vaccine

Question 4

Infliximab

Answer 4

• Remicade
• Biosimilar to Inflectra
• Onset: 3-7 days
• Duration: 6-12 weeks
• Half life: ~102 hours
• Dose: 3 mg/kg IV at 0, 2, and 6 weeks. Then every 8 weeks
• Additional SE: HA/Nausea from infusion (antihistamines)

Question 5

Adalimumab

Answer 5

• Humira
• Biosimilar of Amjevita
• Half life: ~2 weeks
• Dose: 40 mg SQ q2w

Question 6

Golimumab

Answer 6

• Simponi
• Half life: ~2 weeks
• Dose: 50 mg SQ qmonth
• Use with MTX
• Additional SE: URI
• Additional Warning: Tuberculosis
• Additional Monitoring: CBC, S/S CHF

Question 7

Certolizumab Pegol

Answer 7

• Cimzia
• Pegylated
• Half life: ~2 weeks
• Additional SE: Nausea, URI, Headache
• Additional Warning: Tuberculosis
• Additional Monitoring: CBC, S/S CHF

Question 8

Cimzia Dosing

Answer 8

• Initial: 400 mg SQ, repeat in 2 and 4 weeks
• Maintenance: 200 mg qow
• May consider a maintenance dose of 400 mg q4w

Question 9

Anti-TNF Additional Considerations

Answer 9

• Risk of worsening infections, D/C in those with active infection
• May worsen heart failure
• Rare reports of lupus-like symptoms, hepatotoxicity, pancytopenia
• May exacerbate previous MS
• Lack of comparative efficacy and limited long-term safety data
• Reports of pediatric malignancies

Question 10

Anakinra

Answer 10

• Kineret
• Indications: RA, recurrent pericaditis, neonatal-onset multisystem inflammatory disease
• MoA: IL-1 Receptor Antagonist, recombinant protein
• Elimination Half Life: 4-6 hours
• Risk X combos: other immunosuppressives, live vaccines
• ADE: Serious infections, malignancies, neutropenia, anaphylaxis, injection site reactions
• Monitoring: CBC, TB test, Serum creatinine, infections
• ADJUST dose in severely renal impaired
• Don’t use in combo with Anti-TNF
• Reserve for failure of Anti-TNF therapy
• Dose: 100 mg SQ daily

Question 11

Tocilizumab

Answer 11

• Actemra
• IL-6 Receptor Antagonist
• Indications: moderate to severe RA (after Anti-TNF failure), juvenile idiopathic arthritis (JIA)
• MoA: Humanized mAb against the IL-6 receptor, blocks binding and activation by IL-6
• Half life: 6.3 days
• Risk X combinations: other immunosuppressives, live vaccines
• Boxed warning: serious infections
• Other ADE: infusional reactions, lipids, GI perforation
• Monitoring: TB and HBV test, LFTs, lipid panel, CBC, monitor for infections

Question 12

Abatacept

Answer 12

• Orencia
• Indications: RA, JIA
• Target: B7-1/2
• MoA: recombinant fusion protein consisting of CTLA-4 extracellular domain linked to Fc portion of human IgG, binds to target and prevents co-stimulatory signal required for T-cell activation
• Half-life: 13.1 days
• Risk X combos: other immunosuppressives, live vaccines
• Box warnings: serious infections, malignancies
• Other ADE: infusional reactions
• Monitoring: hypersensitivity, infection, TB/HBV test
• Dose: weight dependent, 750 mg IV infusion over 30 minutes, admin at baseline then at 2 and 4 weeks, then every 4 weeks

Question 13

Sarilumab

Answer 13

• Kevzara
• IL-6 receptor antagonist
• Binds soluble and membrane-bound IL-6 receptors, blocks IL-6 signaling and production of CRP
• Indication: moderate to severe RA with inadequate response to Anti-TNF
• Dosing: 200 mg SQ q2w
• Alone or in combination with non-biologic DMARDs
• ADE: infection, TB, GI perforation, neutropenia, thrombocytopenia, hepatotoxicity, plasma lipids, malignancy
• Risk X combos: other immunosuppressives
• Box warnings: serious infections
• Monitor: signs of infection, therapies that increase TG/LDL/HDL, monitor lipids

Question 14

Rituximab

Answer 14

-Rituxan
-Anti-B cell Ab
-MoA: mAb against CD20 on B-cells. CD20 controls cell cycle. Binding to CD20 activates CDCC and ADCC to kill B cells
-Onset: ~ 2 weeks, B-cell depletion lasts at least 6 mo
-Half Life: 18 days
-Risk X combos: other immunosuppressives, live vaccines
-Boxed warnings: Infusion reactions, HepB reactivation, mucocutaneous reactions, progressive multifocal leukoencephalopathy
-Monitoring: CBC, platelets, creatinine, HBV screening, infusion rxns, arrhythmias, bowel
obstruction/perforation, neurologic deficits
-Dosing: 1000 mg IV infusion, separate by 2 weeks
-Premedication with methylprednisolone 100 mg IV
-Use in combination with MTX in moderate to severe RA with inadequate response to Anti-TNF