Safety and tolerability of atogepant for the preventive treatment of migraine: a post hoc analysis of pooled data from four clinical trials
Background Conventional, non-specific preventive migraine treatments often demonstrate low rates of treatment persistence due to poor efficacy or tolerability. Effective, well-tolerated preventive treatments are needed to reduce migraine symptoms, improve function, and enhance quality of life. Atogepant is a migraine-specific oral calcitonin gene–related peptide receptor antagonist that is indicated for the preventive treatment of migraine in adults. This analysis evaluated the safety and tolerability profile of atogepant for the preventive treatment of migraine, including adverse events (AEs) of interest, such as constipation, nausea, hepatic safety, weight changes, and cardiac disorders. Methods This post hoc analysis was performed using data pooled from 2 (12-week) randomized, double-blind, placebo-controlled trials (RCTs) and 2 (40- and 52-week) open-label long-term safety (LTS) trials of oral atogepant for episodic migraine (EM). Results The safety population included 1550 participants from the pooled RCTs (atogepant, n = 1142; placebo, n = 408) and 1424 participants from the pooled LTS trials (atogepant, n = 1228; standard care [SC], n = 196). In total, 643/1142 (56.3%) atogepant participants and 218/408 (53.4%) placebo participants experienced ≥ 1 treatment-emergent AEs (TEAEs) in the RCTs. In the LTS trials, 792/1228 (64.5%) of atogepant participants and 154/196 (78.6%) of SC participants experienced ≥ 1 TEAEs. The most commonly reported TEAEs (≥ 5%) in participants who received atogepant once daily were upper respiratory tract infection (5.3% in RCTs, 7.7% in LTS trials), constipation (6.1% in RCTs, 5.0% in LTS trials), nausea (6.6% in RCTs, 4.6% in LTS trials), and urinary tract infection (3.4% in RCTs, 5.2% in LTS trials). Additionally, weight loss appeared to be dose- and duration-dependent. Most TEAEs were considered unrelated to study drug and few led to discontinuation. Conclusions Overall, atogepant is safe and well tolerated in pooled RCTs and LTS trials for the preventive treatment of EM in adults. Trial registration ClinicalTrials.gov identifiers: NCT02848326 (MD-01), NCT03777059 (ADVANCE), NCT03700320 (study 302), NCT03939312 (study 309). Graphical Abstract.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:25 |
|---|---|
| Enthalten in: |
The journal of headache and pain - 25(2024), 1 vom: 11. März |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Rizzoli, Paul [VerfasserIn] |
|---|
| Links: |
Volltext [kostenfrei] |
|---|
| BKL: | |
|---|---|
| Themen: |
| Anmerkungen: |
© The Author(s) 2024 |
|---|
| doi: |
10.1186/s10194-024-01736-z |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
SPR055091067 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | SPR055091067 | ||
| 003 | DE-627 | ||
| 005 | 20240311095256.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240311s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1186/s10194-024-01736-z |2 doi | |
| 035 | |a (DE-627)SPR055091067 | ||
| 035 | |a (SPR)s10194-024-01736-z-e | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 082 | 0 | 4 | |a 610 |q VZ |
| 082 | 0 | 4 | |a 610 |q VZ |
| 084 | |a 44.90 |2 bkl | ||
| 100 | 1 | |a Rizzoli, Paul |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Safety and tolerability of atogepant for the preventive treatment of migraine: a post hoc analysis of pooled data from four clinical trials |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a © The Author(s) 2024 | ||
| 520 | |a Background Conventional, non-specific preventive migraine treatments often demonstrate low rates of treatment persistence due to poor efficacy or tolerability. Effective, well-tolerated preventive treatments are needed to reduce migraine symptoms, improve function, and enhance quality of life. Atogepant is a migraine-specific oral calcitonin gene–related peptide receptor antagonist that is indicated for the preventive treatment of migraine in adults. This analysis evaluated the safety and tolerability profile of atogepant for the preventive treatment of migraine, including adverse events (AEs) of interest, such as constipation, nausea, hepatic safety, weight changes, and cardiac disorders. Methods This post hoc analysis was performed using data pooled from 2 (12-week) randomized, double-blind, placebo-controlled trials (RCTs) and 2 (40- and 52-week) open-label long-term safety (LTS) trials of oral atogepant for episodic migraine (EM). Results The safety population included 1550 participants from the pooled RCTs (atogepant, n = 1142; placebo, n = 408) and 1424 participants from the pooled LTS trials (atogepant, n = 1228; standard care [SC], n = 196). In total, 643/1142 (56.3%) atogepant participants and 218/408 (53.4%) placebo participants experienced ≥ 1 treatment-emergent AEs (TEAEs) in the RCTs. In the LTS trials, 792/1228 (64.5%) of atogepant participants and 154/196 (78.6%) of SC participants experienced ≥ 1 TEAEs. The most commonly reported TEAEs (≥ 5%) in participants who received atogepant once daily were upper respiratory tract infection (5.3% in RCTs, 7.7% in LTS trials), constipation (6.1% in RCTs, 5.0% in LTS trials), nausea (6.6% in RCTs, 4.6% in LTS trials), and urinary tract infection (3.4% in RCTs, 5.2% in LTS trials). Additionally, weight loss appeared to be dose- and duration-dependent. Most TEAEs were considered unrelated to study drug and few led to discontinuation. Conclusions Overall, atogepant is safe and well tolerated in pooled RCTs and LTS trials for the preventive treatment of EM in adults. Trial registration ClinicalTrials.gov identifiers: NCT02848326 (MD-01), NCT03777059 (ADVANCE), NCT03700320 (study 302), NCT03939312 (study 309). Graphical Abstract | ||
| 650 | 4 | |a Calcitonin gene–related peptide |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Migraine |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Safety |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Tolerability |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Marmura, Michael J. |4 aut | |
| 700 | 1 | |a Robblee, Jennifer |4 aut | |
| 700 | 1 | |a McVige, Jennifer |4 aut | |
| 700 | 1 | |a Sacco, Sara |4 aut | |
| 700 | 1 | |a Nahas, Stephanie J. |4 aut | |
| 700 | 1 | |a Ailani, Jessica |4 aut | |
| 700 | 1 | |a De Abreu Ferreira, Rosa |4 aut | |
| 700 | 1 | |a Ma, Julia |4 aut | |
| 700 | 1 | |a Smith, Jonathan H. |4 aut | |
| 700 | 1 | |a Dabruzzo, Brett |4 aut | |
| 700 | 1 | |a Ashina, Messoud |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t The journal of headache and pain |d Springer Milan, 2000 |g 25(2024), 1 vom: 11. März |w (DE-627)SPR009071415 |w (DE-600)2020168-0 |x 1129-2377 |7 nnns |
| 773 | 1 | 8 | |g volume:25 |g year:2024 |g number:1 |g day:11 |g month:03 |
| 856 | 4 | 0 | |u https://dx.doi.org/10.1186/s10194-024-01736-z |z kostenfrei |3 Volltext |
| 912 | |a GBV_SPRINGER | ||
| 912 | |a SSG-OLC-PHA | ||
| 936 | b | k | |a 44.90 |q VZ |
| 951 | |a AR | ||
| 952 | |d 25 |j 2024 |e 1 |b 11 |c 03 | ||