Table 6 Safety outcomes measured in the studies included

Ashina et al. NCT 02,066,415 [67]

Nasopharyngitis

 placebo^a: 5.67%

 70 mg^{a, d}: 3.16%

 140 mg^{a, d}: 1.60%

2.5% with placebo (pancreatitis, vomiting, cholecystitis, parotitis, urinary tract infection, intervertebral disc protrusion)

3.2% with 70 mg (non−cardiac chest pain, appendicitis, radius fracture, costochondritis, intervertebral disc protrusion, fibroma)

1.1% with 140 mg (abdominal adhesions, abdominal pain)

0% mortality

0,7% with placebo

0% with 70 mg

1.1% with 140 mg

Ferrari et al. FOCUS (NCT03308968) [68]

Injection−site erythema

 placebo^a: 5%

 quarterly^b: 7%

 monthly^c: 6%

Injection site induration

 4%, 4%, 5%, respectively^e

Nasopharyngitis

 4%, 5%, 2%, respectively^e

1% with placebo

 < 1% with quarterly

1% with monthly

Atrial fibrillation, cholelithiasis, clavicle fracture, foot fracture, respiratory fume inhalation, rib fracture, road traffic accident, back pain, nephrolithiasis and vocal cord thickening. None considered treatment related

0% mortality

1% with placebo (chest discomfort, injection−site pain and vulvar cancer)

 < 1%) with quarterly

1% with monthly

(palpitations, fatigue, cholelithiasis, road traffic accidents and temporal arteritis)

Ruff et al. REGAIN (NCT02614261) [69]

Injection site pain

 placebo^a: 4.30%

 120 mg^a: 6.23%

 240 mg^a: 7.09%

Injection site reaction

 2%, 3%, 5%, respectively^f

Nasopharyngitis

 5%, 6%, 3%, respectively^f

1.25% with placebo (iron deficiency anaemia, myocardial infarction, alcoholic pancreatitis, gastritis, cellulitis, osteomyelitis, epistaxis)

1.83% with 120 mg (cholelithiasis, pyelonephritis, laceration, road traffic accident, colon cancer, squamous cell carcinoma, seizure)

2.84% with 240 mg (acute myocardial infarction, unstable angina, cardiac failure congestive, acute pancreatitis, hypokalaemia, seizure, nephrolithiasis, renal colic, pulmonary embolism, urticaria)

0% mortality

No data

Mulleners et al. CONQUER (NCT03559257) [70]

Injection site reaction

 placebo^a: 10%

 120 mg^a: 7%

Constipation

 2%, 2%, respectively^g

Nasopharyngitis

 9%, 7%, respectively^g

Influenza

 3%, 5%, respectively^g

1% with placebo (lower limb fracture, Bechet’s syndrome)

1% with 120 mg (haemorrhoids, tonsillitis)

0% mortality

 < 1% hypersensitivity reaction