Table 1 Recurrence rates for acute treatments for migraine

Sumatriptan [28]

RCT, placebo-controlled

100 mg

Reemergence of moderate or severe headache within 24 h of dosing after initial pain relief (mild or none) at 4 h

Patients who reported pain relief at 4 h

92

17.4%

Placebo

32

12.5%

Sumatriptan [14]

RCT, placebo-controlled

100 mg

Return of moderate or severe headache within 24 h of dosing after initial pain relief at 4 h (measured across 3 attacks)

Patients who reported pain relief at 4 h

1st attack: 196

2nd attack: 194

3rd attack: 179

30%

29%

28%

50 mg

1st attack: 198

2nd attack: 194

3rd attack: 167

34%

29%

34%

25 mg

1st attack: 167

2nd attack: 161

3rd attack: 148

34%

39%

26%

Placebo

1st attack: 34

2nd attack: 25

3rd attack: 22

35%

48%

41%

Frovatriptan [26]

(3 studies combined)

RCT, placebo-controlled

2.5 mg

Grade 3 or 2 headache improving to grade 1 or 0 at 4 h, but subsequently returning to grade 2 or 3 within 24 h of initial dose

Patients who responded at 4 h

1454

10%-25%

Placebo

740

24%-31%

Lasmiditan [3, 29]

(SAMURAI and SPARTAN)

RCT, placebo-controlled, pooled analysis

200 mg

Administration of a second dose if moderate or severe pain returns from 2 to 24 h

Patients who reported pain freedom at 2 h

396

7%

100 mg

337

10%

50 mg

169

8%

Placebo

206

10%

200 mg

Patients who reported none or mild pain at 2 h after the first dose and subsequently reported moderate or severe pain within 24 h

Patients who reported mild or no pain at 2 h

683

14.1%

100 mg

698

15.3%

50 mg

346

15.3%

Placebo

505

17.4%

Lasmiditan [30]

(GLADIATOR)

Open-label, randomized

All doses combined

Number of attacks treated with a second dose up to 48 h after the first dose for recurrence

Patients who reported pain freedom at

2 h (ITT population)

4963

6.1%

200 mg

2665

5.6%

100 mg

2298

6.6%

All doses combined

Number of attacks that had recurrence up to 48 h post-dose

Patients who reported pain freedom at 2 h (mITT population)

NA

17.1%

Rimegepant (ODT) [31]

RCT, placebo-controlled

75 mg

Return of headache (some pain) within 48 h of an initial response to treatment after initial pain freedom at 2 h

Patients who reported pain freedom at 2 h

142

36.6%

Placebo

74

50%

Ubrogepant [32]

(ACHIEVE I)

RCT, placebo-controlled

Rescue

100 mg

50 mg

Placebo

Administration of a second dose of study drug or rescue medication for moderate or severe headache from 2 to 48 h after the initial dose

mITT population

448

423

456

15.2%

16.3%

28.7%

Second Dose

50 mg/100 mg

871

38.6%

Ubrogepant [33]

(ACHIEVE II)

RCT, placebo-controlled

Rescue

50 mg

25 mg

Placebo

Administration of a second dose of study drug or rescue medication for moderate or severe headache from 2 to 24 h after the initial dose

mITT population

NA

NA

NA

16.4%

20.5%

25.7%

Second Dose

25 mg/50 mg

Placebo

899

456

37.6%

42.8%

MAP0004 (FREEDOM-301)

RCT, placebo-controlled, post hoc analysis

1 mg

Return of moderate or severe pain within 24 h or 48 h of dosing (Definition A)

Patients who reported pain relief at 2 h

231

24 h: 6.5%

48 h: 10.4%

Placebo

136

24 h: 14.7%

48 h: 17.6%

1 mg

Return of moderate or severe pain within 24 h or 48 h of dosing OR use of rescue medications (Definition B)

Patients who reported pain relief at 2 h

231

24 h: 21.6%

48 h: 29.4%

Placebo

136

24 h: 39.0%

48 h: 41.2%

1 mg

Return of moderate or severe pain within 24 h or 48 h of dosing (Definition C)

mITT population

397

24 h: 3.8%

48 h: 6.0%

Placebo

397

24 h: 5.0%

48 h: 6.0%

1 mg

Return of moderate or severe pain within 24 h or 48 h of dosing OR use of rescue medications (Definition D)

mITT population

397

24 h: 12.6%

48 h: 17.1%

Placebo

397

24 h: 13.4%

48 h: 14.1%

INP104

(STOP 301) [34]

Open-label

1.45 mg

Onset of a new headache prior to 24 h and 48 h post-dose

Patients who self-reported pain freedom at 2 h

126

24 h: 7.1%

48 h: 14.3%