Table 2.

First Use of Biologic Treatment: Hypotheses and Operational Definitions of Exposure to Biologic Treatment and Comparison Regimens

Hypothesis	Nickname	Exposure started at initiation of…
		Biologic treatment	Comparison regimen
RA
Biologic A is no less safe than Biologic B	Head to head comparison	Biologic A	Biologic B
Biologic A is no less safe than the addition of hydrochloroquine, sulfasalazine or leflunomide to someone who has stepped up from background methotrexate	Methotrexate- step-up comparison	Biologic A	≥ 1 dispensing of methotrexate during baseline, followed by adding or switching to hydrochloroquine, sulfasalazine or sulfasalazine
PsA and AS
Biologic A is no less safe than Biologic B	Head to head comparison	Biologic A	Biologic B
Biologic A is no less safe than methotrexate, sulfasalazine, or sulfasalazine	Non-biologic comparison	Biologic A	Methotrexate, sulfasalazine, or sulfasalazine
IBD
Biologic A is no less safe than switching from 5-aminosalicylate or methotrexate to thiopurine*, oral glucocorticoid, or budesonide	Short-term comparison	Biologic A	Thiopurine
Biologic A is no less safe than thiopurine	Long-term comparison	Biologic A	Thiopurine
PsO
Biologic A is no less safe than Biologic B	Head to head comparison	Biologic A	Biologic B
Biologic A is no less safe than methotrexate	Methotrexate comparison	Biologic A	Methotrexate
Biologic A is no less safe than methotrexate failure by adding or switching to comparison treatments	PsO methotrexate - revision treatment comparison	Biologic A	≥ 1 dispensing of methotrexate during baseline followed by adding or switching to UVB + actinotherapy, psoralen + UVA treatment, oral retinoids, isotretinoin +/− etretinate or large quantity topical glucocorticoid

^*Thiopurine=Azathioprine or 6-mercaptopurine.