Table 3

Adverse events of special interest in randomised controlled trials investigating Janus kinase inhibitors and tumour necrosis factor alpha inhibitors

Study	Population	Risk of bias	Treatment	n	Time point (weeks)	Serious adverse events (%)	Serious infections (%)	Herpes zoster (%)	Tuberculosis (%)	Deep vein thrombosis (%)	Pulmonary embolism (%)	Malignancy, excluding NMSC (%)	Non-melanoma skin cancer (%)	MACE (%)
Rheumatoid arthritis
van Vollenhoven 2012 (ORAL Standard)³⁰	MTX-IR	Low	PLC+MTX (Combination group)	106	24	1.9	0.9	0	0	0				0
			TOFA 5 mg two times per day+MTX	204		5.9	1.5	0	0	0				0
			TOFA 10 mg two times per day+MTX	201		5.0	2.0	3.0	0	0.5				0
			ADA 40 mg EOW+MTX	204		2.5	0	0	0	0				0.5
Fleischmann 2017 (ORAL Strategy)³¹	MTX-IR	Low	TOFA 5 mg two times per day+PLC	384	24	9	2	1	0		0.26	<1	1	0
			TOFA 5 mg two times per day+MTX	376		7	3	2	1		0	0	0	0
			ADA 40 mg EOW+MTX	386		6	2	2	0		0.26	0	<1	1
Taylor 2017 (RA-BEAM)³²	MTX-IR	Low	PLC+MTX	488	24	5	1	<1	0	0*	0*	<1	<1	0
			BARI 4 mg+ MTX	487		5	1	1	0	0.2*	0.2*	<1	0	<1
			ADA 40 mg EOW+MTX	330		2	<1	1	<1	0*	0*	0	0	0
Fleischmann 2018 (SELECT-COMPARE)^{33 34}	MTX-IR	Low	PLC+MTX	651	26	2.9	0.8	0.5	0	0	0.2	0.3		0.5
			UPA 15 mg OD+MTX	651		3.7	1.8	0.8	0.2	0.2	0.2	0	0.5	0
			ADA 40 mg EOW+MTX	327		4.3	1.5	0.3	0	0	0.9	0.3	0.3	0.6
Psoriatic arthritis
Mease 2017 (OPAL Broaden)⁵	csDMARD-IR	Low	PLC±csDMARD	105	12	1	0	0	0	0		0	0	0
			TOFA 5 mg two times per day±csDMARD	107		3	0	1	0	0		2	0	0
			TOFA 10 mg two times per day±csDMARD	104		1	0	0	0	0		0	1	0
			ADA 40 mg EOW±csDMARD	106		1	0	0	0	0		0	0	0
Chronic plaque psoriasis
Bachelez 2015³⁵	Candidates for systemic therapy or phototherapy + PASI >12 + PGA moderate/severe +csDMARD-IR	Low	PLC	107	12	1.9	0	0				0	0	0
			TOFA 5 mg two times per day	329		2.1	0.6	0.3				0	0.3	0.3
			TOFA 10 mg two times per day	330		1.5	0.6	0.6				0.3	0.3	0
			ETA 50 mg twice weekly	335		2.1	0.6	0.6				0	0.6	0.3

*Not reported in original report/supplement/ClinicalTrials.gov, source: FDA Briefing Document Arthritis Advisory Committee Meeting, 23 April 2018, pp. 54–55 (Table 25).
ADA, adalimumab; BARI, baricitinib; csDMARD, conventional synthetic disease-modifying anti-rheumatic drug; EOW, every other week; ETA, etanercept; FDA, Food and Drug Administration; IR, insufficient responder; MACE, major adverse cardiovascular events; NMSC, non-melanoma skin cancer; MTX, methotrexate; PASI, Psoriasis Area and Severity Index; PGA, Physician Global Assessment; PLC, placebo; TOFA, tofacitinib; UPA, upadacitinib.