The pharmacological and clinical aspects behind dose loading of biological disease modifying anti-rheumatic drugs (bDMARDs) in auto-immune rheumatic diseases (AIRDs): rationale and systematic narrative review of clinical evidence

Table 1 Overview of bDMARDs for AIRD, loading schedules (if applicable) and associated costs

Drug class	Drug	Terminal halve life	Authorised with dose-loading in AIRDs / other disease?	Loading schedule	Cost per patient year with loading dose^a	Cost per patient year without loading dose^a	Euro/ % increase medication costs due to dose-loading for full year use
TNFi	Adalimumab	14 days	No / Yes	NA
	Certolizumab	14 days	Yes / NA	400 mg weeks 0,2,4, instead of 200 mg	€14,459	€12,965	€1495 / 11.5%
	Etanercept	3 days	No / Yes	NA
	Golimumab	12 days	No / Yes	NA
	Infliximab (RA)	9 days	Yes / Yes	3 mg/kg weeks 0,2,6 and 14, instead of 8 weekly^b	€12,940	€11,323	€1617 / 12.4%
	Infliximab (PsA/axSpA)	9 days	Yes / Yes	5 mg/kg weeks 0,2,6 and 14, instead of 8 weekly^b	€17,254	€15,097	€2157 / 12.5%
Anti-CD20	Rituximab	6–62 days	No / No	NA
Anti CD80/86	Abatacept i.v.	14 days	Yes / No	750 mg weeks 0,2,4 instead of weeks 0,4^c	€15,996	€14,853	€1143 / 7.1%
	Abatacept s.c.	14 days	Yes / NA	Start with 750 mg i.v. instead of once weekly sc^c	€15,199	€14,056	€1143 / 7.5%
IL-1 receptor antagonist	Anakinra	5 h	No / No	NA
Anti-IL6 receptor	Sarilumab	9 days (initial)	No / No	NA
	Tocilizumab i.v.	3 days	No / No	NA
	Tocilizumab s.c.	13 days	No / No	NA
Anti-IL-17A	Secukinumab 150 mg	27 days	Yes / Yes	Weeks 0,1,2,3,4, instead of monthly	€9357	€7486	€1871 / 20%
	Secukinumab 300 mg	27 days	Yes / Yes	Weeks 0,1,2,3,4, instead of monthly	€18,714	€14,972	€3742 / 20%
	Ixekizumab	13 days	Yes / Yes	160 mg instead of 80 mg week 0	€16,116	€14,965	€1151 / 7.1%
Anti-IL-12/23	Ustekinumab	21 days	Yes / Yes	Additional injection at week 4^c	€16,023	€12,819	€3204 / 20%

^awww.medicijnkosten.nl, costs per patient year in the Netherlands
^b 3 mg/ and 5 mg/kg rounded to 3*100 mg and 4*100 mg vials per infusion
^c of the three weight based doses the middle dose of 750 mg was used
^c 45 mg (< 100 kg bodyweight) was used
Abbreviations: i.v. Intravenous, s.c. Subcutaneous, TNFi TNF inhibitor, AIRDs Auto-Immune Rheumatic Disease, NA Not Applicable, AIRD Auto-immune Rheumatic Diseases