Table 3

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

StudyPopulationRisk of biasTreatmentnTime point
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-IRLowPLC+MTX (Combination group)106241.90.90000
TOFA 5 mg two times per day+MTX2045.91.50000
TOFA 10 mg two times per day+MTX2015.
ADA 40 mg EOW+MTX2042.500000.5
Fleischmann 2017 (ORAL Strategy)31 MTX-IRLowTOFA 5 mg two times per day+PLC3842492100.26<110
TOFA 5 mg two times per day+MTX37673210000
ADA 40 mg EOW+MTX38662200.260<11
Taylor 2017 (RA-BEAM)32 MTX-IRLowPLC+MTX4882451<100*0*<1<10
BARI 4 mg+ MTX48751100.2*0.2*<10<1
ADA 40 mg EOW+MTX3302<11<10*0*000
Fleischmann 2018 (SELECT-COMPARE)33 34 MTX-IRLowPLC+MTX651262.90.80.5000.20.30.5
UPA 15 mg OD+MTX6513.
ADA 40 mg EOW+MTX3274.31.50.3000.
Psoriatic arthritis
Mease 2017 (OPAL Broaden)5 csDMARD-IRLowPLC±csDMARD1051210 0 00000
TOFA 5 mg two times per day±csDMARD10730100200
TOFA 10 mg two times per day±csDMARD10410000010
ADA 40 mg EOW±csDMARD10610000000
Chronic plaque psoriasis
Bachelez 201535 Candidates for systemic therapy or phototherapy
+ PASI >12
+ PGA moderate/severe
TOFA 5 mg two times per day3292.10.60.300.30.3
TOFA 10 mg two times per day3301.
ETA 50 mg twice weekly3352.10.60.600.60.3
  • *Not reported in original report/supplement/, 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.