. 2022 Jun 4;27:86. doi: 10.1186/s40001-022-00716-w

Table 6.

Safety outcomes measured in the studies included

Study	Main adverse events	Serious adverse events	Adverse events leading to treatment discontinuation
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

Data are presented as the percentage of patients presenting any adverse effect

^aMonthly administration for 3 months

^bFirst dose consists of fremanezumab 675 mg and placebo in the remaining 2 months

^cFirst dose consists of fremanezumab 675 mg followed by monthly fremanezumab 225 mg for 2 months

^dErenumab

^e Placebo, fremanezumab quarterly treatment, fremanezumab monthly treatment

^fPlacebo, 120 mg galcanezumab, 240 mg galcanezumab

^gPlacebo, galcanezumab 120 mg