Risk of hepatitis B virus reactivation in rheumatoid arthritis patients undergoing biologic treatment: Extending perspective from old to newer drugs

Table 1 Four classes of immunotherapies licensed to treat rheumatoid arthritis

Class	Mode of action	Drug	Mechanism of action	Route of administration	Therapeutic regimen	Half-life	Major approved indications (FDA)
TNF inhibitors	TNF-α neutralization	Adalimumab (fully human monoclonal IgG1 antibody)	Binding to TNF	SC	40 mg every 2 wk	13 d	RA, JIA, PsA, AS, CD, UC, PP, non radiographic axial SpA
		Golimumab (fully human monoclonal IgG1 antibody)	Binding to soluble and membrane bound TNF	SC	50 mg every 4 wk	13 d	RA, PsA, AS, UC
		Certolizumab (pegilated FabI fragment of a human monoclonal antibody)	Binding to TNF	SC	200 mg every 2 wk or 400 mg monthly	14 d	RA, CD, PsA, AS, non-radiographic axial SpA
		Etanercept (p75 TNF receptor - IgG1 Fc fusion protein	Works as a decoy receptor. It binds to soluble TNF, blocking the binding to its receptor	SC	50 mg weekly or 25 mg twice a week	3-6 d	RA, PsA, AS, poliarticular JIA, PP
		Infliximab (chimeric mouse-human monoclonal IgG1 antibody)	Binding to soluble and membrane bound TNF	IV	3 mg/kg (up to 7.5 mg/kg if not effective) every 8 wk after loading at 0, 2 and 6 wk	9 d	RA, PsA, AS, CD, pediatric CD, UC, pediatric UC, PP
B-cell depletion	B-cell lysis	Rituximab (chimeric mouse-human monoclonal IgG1 antibody)	Binding to CD20 and depletion of CD20+ B cells	IV	Two infusions of 1000 mg 2 wk apart. This can be repeated every 6 mo if symptoms return. Infusions are preceded by IV methylprednisolone to reduce the incidence of infusion reactions	18 d (range 5-76)	BNHL, CLL, RA, GPA, MPA
T-cell inhibition	T-cell costimulation blockade	Abatacept (extracellular domain of CTLA4-IgG1 Fc recumbinant human fusion protein)	Binding to CD80/ CD86, blocking T-cell co-stimulation	IV	500-750-1000 mg infusions (for body weight < 60, between 60 and 100 or > 100 kg) every 4 wk following three loading infusions at 0, 2 and 4 wk	13 d (range 8-25)	RA, poliarticular JIA
				SC	125 mg weekly
IL-6 inhibition	IL-6 receptor blockade	Tocilizumab (humanized monoclonal IgG1 antibody)	Binding to soluble and membrane bound IL-6 receptor	IV	8 mg/kg every 4 wk	10-13 d	RA, poliarticular JIA, sistemic JIA

FDA: Food and Drug Administration; CTLA-4: Cytotoxic T-lymphocyte associated-antigen 4; IL-6: Interleukin 6; IV: Intraveneous injection; PEG: Polyethylene glycol; SC: Subcutaneous; TNF: Tumour necrosis factor; JIA: Juvenile Idiopathic Arthritis; PsA: Psoriatic arthritis; AS: Ankylosing spondylitis; SpA: Spondiloarthritis; CD: Chron’s disease; UC: Ulcerative colitis; PP: Plaque psoriasis; BNHL: B-cell non-Hodgkin lymphoma; CLL: Chronic lymphocytic leukemia; GPA: Granulomatosis with polyangiitis (Wegener’s disease); MPA: Microscopic polyangiitis.