Clinical Edge Journal Scan

Key clinical point: Eptinezumab vs placebo demonstrated significantly greater and sustained improvements in patient-reported overall health, quality of life, and most bothersome symptoms in patients with migraine and 2-4 preventive treatment failures.

Major finding: At week 12, 100 and 300 mg eptinezumab vs placebo led to significantly greater improvements in EQ-5D-5L visual analog scale scores (difference from placebo [Δ] 5.1; P < .001, and Δ 7.5; P < .0001, respectively), 6-item Headache Impact Test total scores (Δ −3.8 and −5.4, respectively; both P < .0001), Migraine-Specific Quality of Life Questionnaire scores (both P < .0001), and patient-identified most bothersome symptoms (both P < .0001), with effects sustained until week 24.

Study details: Findings are from the phase 3b DELIVER trial including 890 adults with episodic/chronic migraine and 2-4 prior preventive treatment failures who were randomly assigned to receive eptinezumab (100/300 mg) or placebo.

Disclosures: The clinical trial and publication was funded by H. Lundbeck A/S. Five authors declared being employees of H. Lundbeck A/S. Three authors reported ties with various sources.

Source: Goadsby PJ et al. Eptinezumab improved patient-reported outcomes and quality of life in patients with migraine and prior preventive treatment failures. Eur J Neurol. 2022 (Dec 30). Doi: 10.1111/ene.15670

Key clinical point: Eptinezumab vs placebo demonstrated significantly greater and sustained improvements in patient-reported overall health, quality of life, and most bothersome symptoms in patients with migraine and 2-4 preventive treatment failures.

Major finding: At week 12, 100 and 300 mg eptinezumab vs placebo led to significantly greater improvements in EQ-5D-5L visual analog scale scores (difference from placebo [Δ] 5.1; P < .001, and Δ 7.5; P < .0001, respectively), 6-item Headache Impact Test total scores (Δ −3.8 and −5.4, respectively; both P < .0001), Migraine-Specific Quality of Life Questionnaire scores (both P < .0001), and patient-identified most bothersome symptoms (both P < .0001), with effects sustained until week 24.

Study details: Findings are from the phase 3b DELIVER trial including 890 adults with episodic/chronic migraine and 2-4 prior preventive treatment failures who were randomly assigned to receive eptinezumab (100/300 mg) or placebo.

Disclosures: The clinical trial and publication was funded by H. Lundbeck A/S. Five authors declared being employees of H. Lundbeck A/S. Three authors reported ties with various sources.

Source: Goadsby PJ et al. Eptinezumab improved patient-reported outcomes and quality of life in patients with migraine and prior preventive treatment failures. Eur J Neurol. 2022 (Dec 30). Doi: 10.1111/ene.15670

Key clinical point: Eptinezumab vs placebo demonstrated significantly greater and sustained improvements in patient-reported overall health, quality of life, and most bothersome symptoms in patients with migraine and 2-4 preventive treatment failures.

Major finding: At week 12, 100 and 300 mg eptinezumab vs placebo led to significantly greater improvements in EQ-5D-5L visual analog scale scores (difference from placebo [Δ] 5.1; P < .001, and Δ 7.5; P < .0001, respectively), 6-item Headache Impact Test total scores (Δ −3.8 and −5.4, respectively; both P < .0001), Migraine-Specific Quality of Life Questionnaire scores (both P < .0001), and patient-identified most bothersome symptoms (both P < .0001), with effects sustained until week 24.

Study details: Findings are from the phase 3b DELIVER trial including 890 adults with episodic/chronic migraine and 2-4 prior preventive treatment failures who were randomly assigned to receive eptinezumab (100/300 mg) or placebo.

Disclosures: The clinical trial and publication was funded by H. Lundbeck A/S. Five authors declared being employees of H. Lundbeck A/S. Three authors reported ties with various sources.

Source: Goadsby PJ et al. Eptinezumab improved patient-reported outcomes and quality of life in patients with migraine and prior preventive treatment failures. Eur J Neurol. 2022 (Dec 30). Doi: 10.1111/ene.15670

Key clinical point: Single session of onabotulinumtoxinA effectively reduced neck and migraine-related disability and pain intensity over 3 months in patients with chronic migraine.

Major finding: OnabotulinumtoxinA significantly reduced Neck Disability Index scores (median −16.5 points; P < .001) and Migraine Disability Assessment scores (median −28 points; P < .001) after 4 weeks. The neck pain intensity and migraine headache intensity reduced by almost half (both P < .001) and the median number of monthly headache days reduced from 20 to 6 days (P < .001) after 3 months of onabotulinumtoxinA treatment.

Study details: This retrospective study included 134 patients with chronic migraine who received one session of onabotulinumtoxinA treatment.

Disclosures: This study did not receive any external funding. The authors declared no conflicts of interest.

Source: Onan D et al. OnabotulinumtoxinA treatment in chronic migraine: Investigation of its effects on disability, headache and neck pain intensity. Toxins (Basel). 2022;15(1):29 (Dec 30). Doi: 10.3390/toxins15010029

Key clinical point: Single session of onabotulinumtoxinA effectively reduced neck and migraine-related disability and pain intensity over 3 months in patients with chronic migraine.

Major finding: OnabotulinumtoxinA significantly reduced Neck Disability Index scores (median −16.5 points; P < .001) and Migraine Disability Assessment scores (median −28 points; P < .001) after 4 weeks. The neck pain intensity and migraine headache intensity reduced by almost half (both P < .001) and the median number of monthly headache days reduced from 20 to 6 days (P < .001) after 3 months of onabotulinumtoxinA treatment.

Study details: This retrospective study included 134 patients with chronic migraine who received one session of onabotulinumtoxinA treatment.

Disclosures: This study did not receive any external funding. The authors declared no conflicts of interest.

Source: Onan D et al. OnabotulinumtoxinA treatment in chronic migraine: Investigation of its effects on disability, headache and neck pain intensity. Toxins (Basel). 2022;15(1):29 (Dec 30). Doi: 10.3390/toxins15010029

Key clinical point: Single session of onabotulinumtoxinA effectively reduced neck and migraine-related disability and pain intensity over 3 months in patients with chronic migraine.

Major finding: OnabotulinumtoxinA significantly reduced Neck Disability Index scores (median −16.5 points; P < .001) and Migraine Disability Assessment scores (median −28 points; P < .001) after 4 weeks. The neck pain intensity and migraine headache intensity reduced by almost half (both P < .001) and the median number of monthly headache days reduced from 20 to 6 days (P < .001) after 3 months of onabotulinumtoxinA treatment.

Study details: This retrospective study included 134 patients with chronic migraine who received one session of onabotulinumtoxinA treatment.

Disclosures: This study did not receive any external funding. The authors declared no conflicts of interest.

Source: Onan D et al. OnabotulinumtoxinA treatment in chronic migraine: Investigation of its effects on disability, headache and neck pain intensity. Toxins (Basel). 2022;15(1):29 (Dec 30). Doi: 10.3390/toxins15010029

Key clinical point: The safety and tolerability of once-daily atogepant observed over 40 weeks in this extension trial aligns with profiles from the pivotal phase 3 trials with no new safety signals identified in patients with episodic migraine.

Major finding: Nearly 63% of patients reported treatment-emergent adverse events, most being mild or moderate, with upper respiratory tract infection (5.5%) and urinary tract infection (5.3%) being most frequent. Treatment discontinuation rates due to lack of efficacy (0.6%) or adverse events (3.6%) were low. No deaths were reported.

Study details: Findings are from the 309-OLEX trial, an open-label extension of phase 3 ADVANCE trial, including 685 patients with episodic migraine with or without aura who received 60 mg atogepant once daily for 40 weeks.

Disclosures: This study was supported by AbbVie Inc. (formerly Allergan). Five authors declared being full-time or former employees of or holding stock or stock options in AbbVie. Several authors reported ties with various sources, including AbbVie.

Source: Klein BC et al. Safety and tolerability results of atogepant for the preventive treatment of episodic migraine from a 40-week, open-label multicenter extension of the phase 3 ADVANCE trial. Cephalalgia. 2023 (Jan 9). Doi: 10.1177/03331024221128250

Key clinical point: The safety and tolerability of once-daily atogepant observed over 40 weeks in this extension trial aligns with profiles from the pivotal phase 3 trials with no new safety signals identified in patients with episodic migraine.

Major finding: Nearly 63% of patients reported treatment-emergent adverse events, most being mild or moderate, with upper respiratory tract infection (5.5%) and urinary tract infection (5.3%) being most frequent. Treatment discontinuation rates due to lack of efficacy (0.6%) or adverse events (3.6%) were low. No deaths were reported.

Study details: Findings are from the 309-OLEX trial, an open-label extension of phase 3 ADVANCE trial, including 685 patients with episodic migraine with or without aura who received 60 mg atogepant once daily for 40 weeks.

Disclosures: This study was supported by AbbVie Inc. (formerly Allergan). Five authors declared being full-time or former employees of or holding stock or stock options in AbbVie. Several authors reported ties with various sources, including AbbVie.

Source: Klein BC et al. Safety and tolerability results of atogepant for the preventive treatment of episodic migraine from a 40-week, open-label multicenter extension of the phase 3 ADVANCE trial. Cephalalgia. 2023 (Jan 9). Doi: 10.1177/03331024221128250

Key clinical point: The safety and tolerability of once-daily atogepant observed over 40 weeks in this extension trial aligns with profiles from the pivotal phase 3 trials with no new safety signals identified in patients with episodic migraine.

Major finding: Nearly 63% of patients reported treatment-emergent adverse events, most being mild or moderate, with upper respiratory tract infection (5.5%) and urinary tract infection (5.3%) being most frequent. Treatment discontinuation rates due to lack of efficacy (0.6%) or adverse events (3.6%) were low. No deaths were reported.

Study details: Findings are from the 309-OLEX trial, an open-label extension of phase 3 ADVANCE trial, including 685 patients with episodic migraine with or without aura who received 60 mg atogepant once daily for 40 weeks.

Disclosures: This study was supported by AbbVie Inc. (formerly Allergan). Five authors declared being full-time or former employees of or holding stock or stock options in AbbVie. Several authors reported ties with various sources, including AbbVie.

Source: Klein BC et al. Safety and tolerability results of atogepant for the preventive treatment of episodic migraine from a 40-week, open-label multicenter extension of the phase 3 ADVANCE trial. Cephalalgia. 2023 (Jan 9). Doi: 10.1177/03331024221128250

Key clinical point: A preconception history of migraine showed no significant association with the risk for spontaneous abortion (SAB); however, routine use of medication, suggesting more severe migraine, may confer a greater SAB risk.

Major finding: Preconception migraine history did not increase the risk for SAB (adjusted hazard ratio [aHR] 1.03; 95% CI 0.91-1.16), but daily migraine medication use (aHR 1.38; 95% CI 0.81-2.35), use of prescription migraine prophylaxis medication (aHR 1.43; 95% CI 0.72-2.84), or analgesic/caffeine medication use (aHR 1.42; 95% CI 0.99-2.04) showed a modest but non-significant association with SAB risk.

Study details: This study evaluated 7890 participants from an ongoing prospective study who conceived during follow-up and had or did not have a preconception diagnosis of migraine or migraine medication use, of which 1537 experienced SAB.

Disclosures: This study was funded by the National Institute of Child Health and Human Development, US National Institutes of Health. The authors declared no conflicts of interest.

Source: Crowe HM et al. Pre‑pregnancy migraine diagnosis, medication use, and spontaneous abortion: A prospective cohort study. J Headache Pain. 2022;23:162 (Dec 20). Doi: 10.1186/s10194-022-01533-6

Key clinical point: A preconception history of migraine showed no significant association with the risk for spontaneous abortion (SAB); however, routine use of medication, suggesting more severe migraine, may confer a greater SAB risk.

Major finding: Preconception migraine history did not increase the risk for SAB (adjusted hazard ratio [aHR] 1.03; 95% CI 0.91-1.16), but daily migraine medication use (aHR 1.38; 95% CI 0.81-2.35), use of prescription migraine prophylaxis medication (aHR 1.43; 95% CI 0.72-2.84), or analgesic/caffeine medication use (aHR 1.42; 95% CI 0.99-2.04) showed a modest but non-significant association with SAB risk.

Study details: This study evaluated 7890 participants from an ongoing prospective study who conceived during follow-up and had or did not have a preconception diagnosis of migraine or migraine medication use, of which 1537 experienced SAB.

Disclosures: This study was funded by the National Institute of Child Health and Human Development, US National Institutes of Health. The authors declared no conflicts of interest.

Source: Crowe HM et al. Pre‑pregnancy migraine diagnosis, medication use, and spontaneous abortion: A prospective cohort study. J Headache Pain. 2022;23:162 (Dec 20). Doi: 10.1186/s10194-022-01533-6

Key clinical point: A preconception history of migraine showed no significant association with the risk for spontaneous abortion (SAB); however, routine use of medication, suggesting more severe migraine, may confer a greater SAB risk.

Major finding: Preconception migraine history did not increase the risk for SAB (adjusted hazard ratio [aHR] 1.03; 95% CI 0.91-1.16), but daily migraine medication use (aHR 1.38; 95% CI 0.81-2.35), use of prescription migraine prophylaxis medication (aHR 1.43; 95% CI 0.72-2.84), or analgesic/caffeine medication use (aHR 1.42; 95% CI 0.99-2.04) showed a modest but non-significant association with SAB risk.

Study details: This study evaluated 7890 participants from an ongoing prospective study who conceived during follow-up and had or did not have a preconception diagnosis of migraine or migraine medication use, of which 1537 experienced SAB.

Disclosures: This study was funded by the National Institute of Child Health and Human Development, US National Institutes of Health. The authors declared no conflicts of interest.

Source: Crowe HM et al. Pre‑pregnancy migraine diagnosis, medication use, and spontaneous abortion: A prospective cohort study. J Headache Pain. 2022;23:162 (Dec 20). Doi: 10.1186/s10194-022-01533-6

Key clinical point: A brief group education and supportive self-management program had no beneficial effects on clinically relevant outcomes in patients with chronic migraine or chronic tension type headache and episodic migraine, with or without medication overuse headache.

Major finding: At 12 months, Headache Impact Test scores (adjusted mean difference [AMD] −0.3; P  =  .56), number of headache days (AMD 0.2; P  =  .234), duration of headache (estimated difference [ED] 0.4; P  =  .361), and headache severity (ED 0.2; P  =  .163) were not significantly different between patients who received self-management intervention vs usual care.

Study details: The data come from CHESS, a randomized controlled trial, including 727 participants with chronic migraine or chronic tension type headache and episodic migraine, with or without medication overuse headache, who received self-management intervention or usual care.

Disclosures: This study was funded by the UK National Institute for Health Research Programme Grants for Applied Research program. Several authors reported receiving grants, personal fees, or honoraria from various sources or owning patent.

Source: Underwood M et al. A supportive self-management program for people with chronic headaches and migraine: A randomized controlled trial and economic evaluation. Neurology. 2022 (Dec 16). Doi: 10.1212/WNL.0000000000201518

Key clinical point: A brief group education and supportive self-management program had no beneficial effects on clinically relevant outcomes in patients with chronic migraine or chronic tension type headache and episodic migraine, with or without medication overuse headache.

Major finding: At 12 months, Headache Impact Test scores (adjusted mean difference [AMD] −0.3; P  =  .56), number of headache days (AMD 0.2; P  =  .234), duration of headache (estimated difference [ED] 0.4; P  =  .361), and headache severity (ED 0.2; P  =  .163) were not significantly different between patients who received self-management intervention vs usual care.

Study details: The data come from CHESS, a randomized controlled trial, including 727 participants with chronic migraine or chronic tension type headache and episodic migraine, with or without medication overuse headache, who received self-management intervention or usual care.

Disclosures: This study was funded by the UK National Institute for Health Research Programme Grants for Applied Research program. Several authors reported receiving grants, personal fees, or honoraria from various sources or owning patent.

Source: Underwood M et al. A supportive self-management program for people with chronic headaches and migraine: A randomized controlled trial and economic evaluation. Neurology. 2022 (Dec 16). Doi: 10.1212/WNL.0000000000201518

Key clinical point: A brief group education and supportive self-management program had no beneficial effects on clinically relevant outcomes in patients with chronic migraine or chronic tension type headache and episodic migraine, with or without medication overuse headache.

Major finding: At 12 months, Headache Impact Test scores (adjusted mean difference [AMD] −0.3; P  =  .56), number of headache days (AMD 0.2; P  =  .234), duration of headache (estimated difference [ED] 0.4; P  =  .361), and headache severity (ED 0.2; P  =  .163) were not significantly different between patients who received self-management intervention vs usual care.

Study details: The data come from CHESS, a randomized controlled trial, including 727 participants with chronic migraine or chronic tension type headache and episodic migraine, with or without medication overuse headache, who received self-management intervention or usual care.

Disclosures: This study was funded by the UK National Institute for Health Research Programme Grants for Applied Research program. Several authors reported receiving grants, personal fees, or honoraria from various sources or owning patent.

Source: Underwood M et al. A supportive self-management program for people with chronic headaches and migraine: A randomized controlled trial and economic evaluation. Neurology. 2022 (Dec 16). Doi: 10.1212/WNL.0000000000201518

Key clinical point: Erenumab and onabotulinumtoxinA (onabotA) dual therapy appeared less effective than erenumab alone in patients with chronic migraine.

Major finding: After 12 weeks, patients who were taking onabotA while initiating erenumab and maintained it as dual therapy (WBT) vs those who received erenumab alone (NoBT) had a lower reduction in mean monthly headache days (MHD; 4.7 vs 8.21 days; P  =  .009) and lower mean percentage improvement in MHD (21.7% vs 35.0%; P  =  .001), with a similar trend being observed among patients who were on onabotA while initiating erenumab but discontinued onabotA (WoBT).

Study details: This retrospective cohort study included 187 patients with chronic migraine who received WBT (n = 73), WoBT (n = 44), or NoBT (n = 70).

Disclosures: This study did not receive any specific funding. A Jaimes and J Rodríguez-Vico declared receiving honoraria or speaking fees from AbbVie and other sources.

Source: Jaimes A et al. Dual therapy with Erenumab and onabotulinumtoxinA: No synergistic effect in chronic migraine: A retrospective cohort study. Pain Pract. 2022 (Dec 12). Doi: 10.1111/papr.13196

Key clinical point: Erenumab and onabotulinumtoxinA (onabotA) dual therapy appeared less effective than erenumab alone in patients with chronic migraine.

Major finding: After 12 weeks, patients who were taking onabotA while initiating erenumab and maintained it as dual therapy (WBT) vs those who received erenumab alone (NoBT) had a lower reduction in mean monthly headache days (MHD; 4.7 vs 8.21 days; P  =  .009) and lower mean percentage improvement in MHD (21.7% vs 35.0%; P  =  .001), with a similar trend being observed among patients who were on onabotA while initiating erenumab but discontinued onabotA (WoBT).

Study details: This retrospective cohort study included 187 patients with chronic migraine who received WBT (n = 73), WoBT (n = 44), or NoBT (n = 70).

Disclosures: This study did not receive any specific funding. A Jaimes and J Rodríguez-Vico declared receiving honoraria or speaking fees from AbbVie and other sources.

Source: Jaimes A et al. Dual therapy with Erenumab and onabotulinumtoxinA: No synergistic effect in chronic migraine: A retrospective cohort study. Pain Pract. 2022 (Dec 12). Doi: 10.1111/papr.13196

Key clinical point: Erenumab and onabotulinumtoxinA (onabotA) dual therapy appeared less effective than erenumab alone in patients with chronic migraine.

Major finding: After 12 weeks, patients who were taking onabotA while initiating erenumab and maintained it as dual therapy (WBT) vs those who received erenumab alone (NoBT) had a lower reduction in mean monthly headache days (MHD; 4.7 vs 8.21 days; P  =  .009) and lower mean percentage improvement in MHD (21.7% vs 35.0%; P  =  .001), with a similar trend being observed among patients who were on onabotA while initiating erenumab but discontinued onabotA (WoBT).

Study details: This retrospective cohort study included 187 patients with chronic migraine who received WBT (n = 73), WoBT (n = 44), or NoBT (n = 70).

Disclosures: This study did not receive any specific funding. A Jaimes and J Rodríguez-Vico declared receiving honoraria or speaking fees from AbbVie and other sources.

Source: Jaimes A et al. Dual therapy with Erenumab and onabotulinumtoxinA: No synergistic effect in chronic migraine: A retrospective cohort study. Pain Pract. 2022 (Dec 12). Doi: 10.1111/papr.13196

Key clinical point: Erenumab and onabotulinumtoxinA (onabotA) dual therapy appeared less effective than erenumab alone in patients with chronic migraine.

Major finding: After 12 weeks, patients who were taking onabotA while initiating erenumab and maintained it as dual therapy (WBT) vs those who received erenumab alone (NoBT) had a lower reduction in mean monthly headache days (MHD; 4.7 vs 8.21 days; P  =  .009) and lower mean percentage improvement in MHD (21.7% vs 35.0%; P  =  .001), with a similar trend being observed among patients who were on onabotA while initiating erenumab but discontinued onabotA (WoBT).

Study details: This retrospective cohort study included 187 patients with chronic migraine who received WBT (n = 73), WoBT (n = 44), or NoBT (n = 70).

Disclosures: This study did not receive any specific funding. A Jaimes and J Rodríguez-Vico declared receiving honoraria or speaking fees from AbbVie and other sources.

Source: Jaimes A et al. Dual therapy with Erenumab and onabotulinumtoxinA: No synergistic effect in chronic migraine: A retrospective cohort study. Pain Pract. 2022 (Dec 12). Doi: 10.1111/papr.13196

Key clinical point: Erenumab and onabotulinumtoxinA (onabotA) dual therapy appeared less effective than erenumab alone in patients with chronic migraine.

Major finding: After 12 weeks, patients who were taking onabotA while initiating erenumab and maintained it as dual therapy (WBT) vs those who received erenumab alone (NoBT) had a lower reduction in mean monthly headache days (MHD; 4.7 vs 8.21 days; P  =  .009) and lower mean percentage improvement in MHD (21.7% vs 35.0%; P  =  .001), with a similar trend being observed among patients who were on onabotA while initiating erenumab but discontinued onabotA (WoBT).

Study details: This retrospective cohort study included 187 patients with chronic migraine who received WBT (n = 73), WoBT (n = 44), or NoBT (n = 70).

Disclosures: This study did not receive any specific funding. A Jaimes and J Rodríguez-Vico declared receiving honoraria or speaking fees from AbbVie and other sources.

Source: Jaimes A et al. Dual therapy with Erenumab and onabotulinumtoxinA: No synergistic effect in chronic migraine: A retrospective cohort study. Pain Pract. 2022 (Dec 12). Doi: 10.1111/papr.13196

Key clinical point: Erenumab and onabotulinumtoxinA (onabotA) dual therapy appeared less effective than erenumab alone in patients with chronic migraine.

Major finding: After 12 weeks, patients who were taking onabotA while initiating erenumab and maintained it as dual therapy (WBT) vs those who received erenumab alone (NoBT) had a lower reduction in mean monthly headache days (MHD; 4.7 vs 8.21 days; P  =  .009) and lower mean percentage improvement in MHD (21.7% vs 35.0%; P  =  .001), with a similar trend being observed among patients who were on onabotA while initiating erenumab but discontinued onabotA (WoBT).

Study details: This retrospective cohort study included 187 patients with chronic migraine who received WBT (n = 73), WoBT (n = 44), or NoBT (n = 70).

Disclosures: This study did not receive any specific funding. A Jaimes and J Rodríguez-Vico declared receiving honoraria or speaking fees from AbbVie and other sources.

Source: Jaimes A et al. Dual therapy with Erenumab and onabotulinumtoxinA: No synergistic effect in chronic migraine: A retrospective cohort study. Pain Pract. 2022 (Dec 12). Doi: 10.1111/papr.13196

Key clinical point: Youth with continuous headache from migraine, persistent post-traumatic headache (PPTH), and new daily persistent headache (NDPH) presented remarkably similar headache features, with most PPTH and NDPH cases resembling abrupt onset of migraine.

Major finding: Youths with migraine, PPTH, and NDPH had similar median usual headache severity score (P  =  .55), similar frequency of bad headaches (P  =  .63), and similar raw Pediatric Migraine Disability Assessment score (P  =  .28). Overall, 72% youths with PPTH and 64% of youths with NDPH met all four diagnostic criteria for migraine.

Study details: This cross-sectional study included 150 age- and sex-matched youths with continuous headache from migraine, PPTH, or NDPH who had prior exposure to ≤2 preventive medications.

Disclosures: This study was supported by the National Institute of Neurological Disorders and Stroke of the US National Institutes of Health and other sources. All authors declared receiving research grants, salary support, or compensation for serving as consultants for or owning stock options in various sources.

Source: Gentile CP et al. Comparison of continuous headache features in youth with migraine, new daily persistent headache, and persistent post-traumatic headache. Cephalalgia. 2023 (Jan 1). Doi: 10.1177/03331024221131331

Key clinical point: Youth with continuous headache from migraine, persistent post-traumatic headache (PPTH), and new daily persistent headache (NDPH) presented remarkably similar headache features, with most PPTH and NDPH cases resembling abrupt onset of migraine.

Major finding: Youths with migraine, PPTH, and NDPH had similar median usual headache severity score (P  =  .55), similar frequency of bad headaches (P  =  .63), and similar raw Pediatric Migraine Disability Assessment score (P  =  .28). Overall, 72% youths with PPTH and 64% of youths with NDPH met all four diagnostic criteria for migraine.

Study details: This cross-sectional study included 150 age- and sex-matched youths with continuous headache from migraine, PPTH, or NDPH who had prior exposure to ≤2 preventive medications.

Disclosures: This study was supported by the National Institute of Neurological Disorders and Stroke of the US National Institutes of Health and other sources. All authors declared receiving research grants, salary support, or compensation for serving as consultants for or owning stock options in various sources.

Source: Gentile CP et al. Comparison of continuous headache features in youth with migraine, new daily persistent headache, and persistent post-traumatic headache. Cephalalgia. 2023 (Jan 1). Doi: 10.1177/03331024221131331

Key clinical point: Youth with continuous headache from migraine, persistent post-traumatic headache (PPTH), and new daily persistent headache (NDPH) presented remarkably similar headache features, with most PPTH and NDPH cases resembling abrupt onset of migraine.

Major finding: Youths with migraine, PPTH, and NDPH had similar median usual headache severity score (P  =  .55), similar frequency of bad headaches (P  =  .63), and similar raw Pediatric Migraine Disability Assessment score (P  =  .28). Overall, 72% youths with PPTH and 64% of youths with NDPH met all four diagnostic criteria for migraine.

Study details: This cross-sectional study included 150 age- and sex-matched youths with continuous headache from migraine, PPTH, or NDPH who had prior exposure to ≤2 preventive medications.

Disclosures: This study was supported by the National Institute of Neurological Disorders and Stroke of the US National Institutes of Health and other sources. All authors declared receiving research grants, salary support, or compensation for serving as consultants for or owning stock options in various sources.

Source: Gentile CP et al. Comparison of continuous headache features in youth with migraine, new daily persistent headache, and persistent post-traumatic headache. Cephalalgia. 2023 (Jan 1). Doi: 10.1177/03331024221131331

Several recent studies have assessed the use of glucocorticoids, a frequent companion to disease-modifying antirheumatic drug (DMARD) and biologic therapy. Many patients are treated with glucocorticoids early in their disease course as a bridging therapy to long-term treatment, and others receive glucocorticoid therapy chronically or intermittently for flares. Van Ouwerkerk and colleagues performed a combined analysis of seven clinical trials, identified in a systematic literature review, that included a glucocorticoid taper protocol for the treatment of newly diagnosed rheumatoid arthritis (RA), undifferentiated arthritis, or "high-risk profile for persistent arthritis." These studies encompassed intravenous, intramuscular, and oral glucocorticoid regimens, and the continued use of glucocorticoids after bridging. These regimens, including cumulative doses, were examined and found to result in a low probability of ongoing use, especially in patients with lower initial doses and shorter bridging schedules. However, though reassuring as to the early use of glucocorticoids in clinical practice, this finding can be affected by patient characteristics not examined in detail in the aggregated results, including whether the patients were classified as having RA, undifferentiated arthritis, or a "high-risk profile."

Adami and colleagues also looked at tapering of glucocorticoids in patients with RA (though not necessarily early RA) in order to determine risk for flare associated with different tapering schedules. They examined the characteristics of patients with RA experiencing a flare (defined as an increase in Disease Activity Score 28 for Rheumatoid Arthritis with C-reactive protein [DAS28-CRP] > 1.2) and their glucocorticoid therapy in the preceding 6 months and found that tapering to a prednisone equivalent ≤ 2.5 mg daily was associated with a higher risk for flare but that doses > 2.5 mg daily were not. Though this finding is perhaps expected, it does not provide further insight into a strategy to minimize the associated adverse effects of glucocorticoid therapy.

Adding further weight to this point is a study performed in Denmark by Dieperink and colleagues examining risk for Staphylococcus aureus bacteremia (SAB) using a nation-wide registry of over 30,000 patients with RA. They found 180 cases of SAB and examined the patient characteristics. Patients who were currently using or previously used a biologic DMARD had an increased risk for SAB as well as those with moderate to high RA disease activity. Study participants who were currently using a prednisone-equivalent of ≤ 7.5 mg daily had an adjusted odds ratio (aOR) of 2.2 and those using > 7.5 mg daily had an aOR of 9.5 for SAB. This concerning finding suggests that even a relatively "low" dose of prednisone use is not benign for patients with RA, and these studies bring to light the need to research optimal strategies for disease control and balancing immunosuppression with the risk for infection and other adverse events.

Heckert and colleagues looked at another aspect of RA disease control, namely, local progression in a single affected joint. Their prior work has suggested that patients with RA may be prone to recurrent inflammation in a single joint despite systemic treatment, a finding that aligns with common clinical observations. This study evaluates radiographic progression in susceptible joints via post hoc analysis using data from the BeSt study including tender and swollen joints, hand and foot radiographs, and disease activity scores. Despite systemic treatment to a target low disease activity or remission state (as per the BeSt protocol), the study found an association between recurrent joint inflammation and radiographic progression (ie, erosions). However, because they only looked at hand and foot joints, the strength of this association in other joints is unknown, as is the use of local treatment, such as steroid injection to minimize inflammation, though both questions may be difficult to evaluate in a small prospective study.

Several recent studies have assessed the use of glucocorticoids, a frequent companion to disease-modifying antirheumatic drug (DMARD) and biologic therapy. Many patients are treated with glucocorticoids early in their disease course as a bridging therapy to long-term treatment, and others receive glucocorticoid therapy chronically or intermittently for flares. Van Ouwerkerk and colleagues performed a combined analysis of seven clinical trials, identified in a systematic literature review, that included a glucocorticoid taper protocol for the treatment of newly diagnosed rheumatoid arthritis (RA), undifferentiated arthritis, or "high-risk profile for persistent arthritis." These studies encompassed intravenous, intramuscular, and oral glucocorticoid regimens, and the continued use of glucocorticoids after bridging. These regimens, including cumulative doses, were examined and found to result in a low probability of ongoing use, especially in patients with lower initial doses and shorter bridging schedules. However, though reassuring as to the early use of glucocorticoids in clinical practice, this finding can be affected by patient characteristics not examined in detail in the aggregated results, including whether the patients were classified as having RA, undifferentiated arthritis, or a "high-risk profile."

Adami and colleagues also looked at tapering of glucocorticoids in patients with RA (though not necessarily early RA) in order to determine risk for flare associated with different tapering schedules. They examined the characteristics of patients with RA experiencing a flare (defined as an increase in Disease Activity Score 28 for Rheumatoid Arthritis with C-reactive protein [DAS28-CRP] > 1.2) and their glucocorticoid therapy in the preceding 6 months and found that tapering to a prednisone equivalent ≤ 2.5 mg daily was associated with a higher risk for flare but that doses > 2.5 mg daily were not. Though this finding is perhaps expected, it does not provide further insight into a strategy to minimize the associated adverse effects of glucocorticoid therapy.

Adding further weight to this point is a study performed in Denmark by Dieperink and colleagues examining risk for Staphylococcus aureus bacteremia (SAB) using a nation-wide registry of over 30,000 patients with RA. They found 180 cases of SAB and examined the patient characteristics. Patients who were currently using or previously used a biologic DMARD had an increased risk for SAB as well as those with moderate to high RA disease activity. Study participants who were currently using a prednisone-equivalent of ≤ 7.5 mg daily had an adjusted odds ratio (aOR) of 2.2 and those using > 7.5 mg daily had an aOR of 9.5 for SAB. This concerning finding suggests that even a relatively "low" dose of prednisone use is not benign for patients with RA, and these studies bring to light the need to research optimal strategies for disease control and balancing immunosuppression with the risk for infection and other adverse events.

Heckert and colleagues looked at another aspect of RA disease control, namely, local progression in a single affected joint. Their prior work has suggested that patients with RA may be prone to recurrent inflammation in a single joint despite systemic treatment, a finding that aligns with common clinical observations. This study evaluates radiographic progression in susceptible joints via post hoc analysis using data from the BeSt study including tender and swollen joints, hand and foot radiographs, and disease activity scores. Despite systemic treatment to a target low disease activity or remission state (as per the BeSt protocol), the study found an association between recurrent joint inflammation and radiographic progression (ie, erosions). However, because they only looked at hand and foot joints, the strength of this association in other joints is unknown, as is the use of local treatment, such as steroid injection to minimize inflammation, though both questions may be difficult to evaluate in a small prospective study.

Several recent studies have assessed the use of glucocorticoids, a frequent companion to disease-modifying antirheumatic drug (DMARD) and biologic therapy. Many patients are treated with glucocorticoids early in their disease course as a bridging therapy to long-term treatment, and others receive glucocorticoid therapy chronically or intermittently for flares. Van Ouwerkerk and colleagues performed a combined analysis of seven clinical trials, identified in a systematic literature review, that included a glucocorticoid taper protocol for the treatment of newly diagnosed rheumatoid arthritis (RA), undifferentiated arthritis, or "high-risk profile for persistent arthritis." These studies encompassed intravenous, intramuscular, and oral glucocorticoid regimens, and the continued use of glucocorticoids after bridging. These regimens, including cumulative doses, were examined and found to result in a low probability of ongoing use, especially in patients with lower initial doses and shorter bridging schedules. However, though reassuring as to the early use of glucocorticoids in clinical practice, this finding can be affected by patient characteristics not examined in detail in the aggregated results, including whether the patients were classified as having RA, undifferentiated arthritis, or a "high-risk profile."

Adami and colleagues also looked at tapering of glucocorticoids in patients with RA (though not necessarily early RA) in order to determine risk for flare associated with different tapering schedules. They examined the characteristics of patients with RA experiencing a flare (defined as an increase in Disease Activity Score 28 for Rheumatoid Arthritis with C-reactive protein [DAS28-CRP] > 1.2) and their glucocorticoid therapy in the preceding 6 months and found that tapering to a prednisone equivalent ≤ 2.5 mg daily was associated with a higher risk for flare but that doses > 2.5 mg daily were not. Though this finding is perhaps expected, it does not provide further insight into a strategy to minimize the associated adverse effects of glucocorticoid therapy.

Adding further weight to this point is a study performed in Denmark by Dieperink and colleagues examining risk for Staphylococcus aureus bacteremia (SAB) using a nation-wide registry of over 30,000 patients with RA. They found 180 cases of SAB and examined the patient characteristics. Patients who were currently using or previously used a biologic DMARD had an increased risk for SAB as well as those with moderate to high RA disease activity. Study participants who were currently using a prednisone-equivalent of ≤ 7.5 mg daily had an adjusted odds ratio (aOR) of 2.2 and those using > 7.5 mg daily had an aOR of 9.5 for SAB. This concerning finding suggests that even a relatively "low" dose of prednisone use is not benign for patients with RA, and these studies bring to light the need to research optimal strategies for disease control and balancing immunosuppression with the risk for infection and other adverse events.

Heckert and colleagues looked at another aspect of RA disease control, namely, local progression in a single affected joint. Their prior work has suggested that patients with RA may be prone to recurrent inflammation in a single joint despite systemic treatment, a finding that aligns with common clinical observations. This study evaluates radiographic progression in susceptible joints via post hoc analysis using data from the BeSt study including tender and swollen joints, hand and foot radiographs, and disease activity scores. Despite systemic treatment to a target low disease activity or remission state (as per the BeSt protocol), the study found an association between recurrent joint inflammation and radiographic progression (ie, erosions). However, because they only looked at hand and foot joints, the strength of this association in other joints is unknown, as is the use of local treatment, such as steroid injection to minimize inflammation, though both questions may be difficult to evaluate in a small prospective study.

Poly-(ADP-ribose) polymerase (PARP) inhibitors have emerged as essential therapeutic agents in patients with germline BRCA1/2-mutated BC. A BRCA-like phenotype is displayed by a large subset of patients with germline BRCA1/2-wildtype BC who present with homologous recombination deficiency (HRD). The randomized phase 2 S1416 trial (Rodler et al) evaluated the efficacy of cisplatin combined with the PARP inhibitor veliparib in three cohorts of metastatic BC: mutated germline BRCA1/2, BRCA-like, and non-BRCA–like. A total of 335 patients with metastatic or recurrent triple-negative BC (TNBC) or germline BRCA1/2-mutated metastatic BC were randomly assigned (1:1) to receive cisplatin plus either veliparib or a matching placebo. The findings showed that the addition of veliparib to cisplatin significantly improved progression-free survival (PFS) in patients with BRCA-like metastatic TNBC compared with placebo (5.9 vs 4.2 months; HR 0.57; log-rank P = .01), but not in mutated germline BRCA1/2 (6.2 vs 6.4 months; P = .54) and non-BRCA–like (4.0 vs 3.0 months; P = .57) groups. No new toxicity signals were observed. These findings suggest BRCA-like TNBC might show sensitivity to PARP inhibitors and therefore these agents should be explored further in this cohort.

A recent update from the combined analysis of the SOFT and TEXT studies comparing outcomes in 4690 premenopausal women with estrogen/progesterone receptor–positive early BC (Pagani et al) showed that exemestane plus ovarian function suppression (OFS) led to a greater reduction in recurrence risk compared with tamoxifen plus OFS in premenopausal women. After a median follow-up of 13 years, results showed a 4.6% absolute improvement in 12-year disease-free survival (HR 0.79; P < .001) and a 1.8% absolute improvement in disease recurrence-free interval (HR 0.83; P = .03) with exemestane plus OFS compared with tamoxifen plus OFS. These treatment effects on recurrence began to attenuate over time, being strongest in the first 5 years with no further improvement after 10 or more years. No improvement in overall survival (OS) was noted with exemestane vs tamoxifen, although both arms had excellent survival outcomes (90.1% vs 89.1%; HR 0.93; 95% CI 0.78-1.11). It is important to note that there was a 3.3% absolute improvement in 12-year OS with exemestane plus OFS among patients with HER2-negative tumors who received chemotherapy. This OS benefit was also noted amongst patients with high-risk clinicopathologic characteristics (<35 years and those with > 2 cm or grade 3 tumors), ranging from 4.0% to 5.5% absolute improvement. In conclusion, sustained recurrence risk reductions were noted with adjuvant exemestane plus OFS compared with tamoxifen plus OFS, with the most clinically meaningful survival benefit noted for patients with higher risk tumors. Proper selection of patients who are most likely to benefit from exemestane over tamoxifen is vital to maximize the survival benefit while minimizing the burden of treatment intensification.

Findings from a retrospective study including 221 women with BC who received preoperative neoadjuvant chemotherapy (NAC) showed that the presence of metabolic syndrome (MetS) worsened survival outcomes and increased disease recurrence risk (Zhou et al). Patients were divided into MetS and non-MetS groups according to National Cholesterol Education Program Adult Treatment Panel III criteria to investigate the association between MetS and clinicopathologic characteristics, pathologic complete response (pCR), and long-term survival. The MetS group had a significantly lower likelihood of achieving pCR after NAC compared with the non-MetS group (odds ratio [OR] 0.316; P = .028), with the risk for death (OR 2.587; P = .004) and disease recurrence (OR 2.228; P = .007) being significantly higher in patients with vs without MetS. In a multivariate analysis, MetS (P = 0.028) and hormone receptors status were independent predictors of pCR after NAC in BC. These findings emphasize the importance of timely intervention of metabolic syndrome to improve outcomes in patients with BC.

Poly-(ADP-ribose) polymerase (PARP) inhibitors have emerged as essential therapeutic agents in patients with germline BRCA1/2-mutated BC. A BRCA-like phenotype is displayed by a large subset of patients with germline BRCA1/2-wildtype BC who present with homologous recombination deficiency (HRD). The randomized phase 2 S1416 trial (Rodler et al) evaluated the efficacy of cisplatin combined with the PARP inhibitor veliparib in three cohorts of metastatic BC: mutated germline BRCA1/2, BRCA-like, and non-BRCA–like. A total of 335 patients with metastatic or recurrent triple-negative BC (TNBC) or germline BRCA1/2-mutated metastatic BC were randomly assigned (1:1) to receive cisplatin plus either veliparib or a matching placebo. The findings showed that the addition of veliparib to cisplatin significantly improved progression-free survival (PFS) in patients with BRCA-like metastatic TNBC compared with placebo (5.9 vs 4.2 months; HR 0.57; log-rank P = .01), but not in mutated germline BRCA1/2 (6.2 vs 6.4 months; P = .54) and non-BRCA–like (4.0 vs 3.0 months; P = .57) groups. No new toxicity signals were observed. These findings suggest BRCA-like TNBC might show sensitivity to PARP inhibitors and therefore these agents should be explored further in this cohort.

A recent update from the combined analysis of the SOFT and TEXT studies comparing outcomes in 4690 premenopausal women with estrogen/progesterone receptor–positive early BC (Pagani et al) showed that exemestane plus ovarian function suppression (OFS) led to a greater reduction in recurrence risk compared with tamoxifen plus OFS in premenopausal women. After a median follow-up of 13 years, results showed a 4.6% absolute improvement in 12-year disease-free survival (HR 0.79; P < .001) and a 1.8% absolute improvement in disease recurrence-free interval (HR 0.83; P = .03) with exemestane plus OFS compared with tamoxifen plus OFS. These treatment effects on recurrence began to attenuate over time, being strongest in the first 5 years with no further improvement after 10 or more years. No improvement in overall survival (OS) was noted with exemestane vs tamoxifen, although both arms had excellent survival outcomes (90.1% vs 89.1%; HR 0.93; 95% CI 0.78-1.11). It is important to note that there was a 3.3% absolute improvement in 12-year OS with exemestane plus OFS among patients with HER2-negative tumors who received chemotherapy. This OS benefit was also noted amongst patients with high-risk clinicopathologic characteristics (<35 years and those with > 2 cm or grade 3 tumors), ranging from 4.0% to 5.5% absolute improvement. In conclusion, sustained recurrence risk reductions were noted with adjuvant exemestane plus OFS compared with tamoxifen plus OFS, with the most clinically meaningful survival benefit noted for patients with higher risk tumors. Proper selection of patients who are most likely to benefit from exemestane over tamoxifen is vital to maximize the survival benefit while minimizing the burden of treatment intensification.

Findings from a retrospective study including 221 women with BC who received preoperative neoadjuvant chemotherapy (NAC) showed that the presence of metabolic syndrome (MetS) worsened survival outcomes and increased disease recurrence risk (Zhou et al). Patients were divided into MetS and non-MetS groups according to National Cholesterol Education Program Adult Treatment Panel III criteria to investigate the association between MetS and clinicopathologic characteristics, pathologic complete response (pCR), and long-term survival. The MetS group had a significantly lower likelihood of achieving pCR after NAC compared with the non-MetS group (odds ratio [OR] 0.316; P = .028), with the risk for death (OR 2.587; P = .004) and disease recurrence (OR 2.228; P = .007) being significantly higher in patients with vs without MetS. In a multivariate analysis, MetS (P = 0.028) and hormone receptors status were independent predictors of pCR after NAC in BC. These findings emphasize the importance of timely intervention of metabolic syndrome to improve outcomes in patients with BC.

Poly-(ADP-ribose) polymerase (PARP) inhibitors have emerged as essential therapeutic agents in patients with germline BRCA1/2-mutated BC. A BRCA-like phenotype is displayed by a large subset of patients with germline BRCA1/2-wildtype BC who present with homologous recombination deficiency (HRD). The randomized phase 2 S1416 trial (Rodler et al) evaluated the efficacy of cisplatin combined with the PARP inhibitor veliparib in three cohorts of metastatic BC: mutated germline BRCA1/2, BRCA-like, and non-BRCA–like. A total of 335 patients with metastatic or recurrent triple-negative BC (TNBC) or germline BRCA1/2-mutated metastatic BC were randomly assigned (1:1) to receive cisplatin plus either veliparib or a matching placebo. The findings showed that the addition of veliparib to cisplatin significantly improved progression-free survival (PFS) in patients with BRCA-like metastatic TNBC compared with placebo (5.9 vs 4.2 months; HR 0.57; log-rank P = .01), but not in mutated germline BRCA1/2 (6.2 vs 6.4 months; P = .54) and non-BRCA–like (4.0 vs 3.0 months; P = .57) groups. No new toxicity signals were observed. These findings suggest BRCA-like TNBC might show sensitivity to PARP inhibitors and therefore these agents should be explored further in this cohort.

A recent update from the combined analysis of the SOFT and TEXT studies comparing outcomes in 4690 premenopausal women with estrogen/progesterone receptor–positive early BC (Pagani et al) showed that exemestane plus ovarian function suppression (OFS) led to a greater reduction in recurrence risk compared with tamoxifen plus OFS in premenopausal women. After a median follow-up of 13 years, results showed a 4.6% absolute improvement in 12-year disease-free survival (HR 0.79; P < .001) and a 1.8% absolute improvement in disease recurrence-free interval (HR 0.83; P = .03) with exemestane plus OFS compared with tamoxifen plus OFS. These treatment effects on recurrence began to attenuate over time, being strongest in the first 5 years with no further improvement after 10 or more years. No improvement in overall survival (OS) was noted with exemestane vs tamoxifen, although both arms had excellent survival outcomes (90.1% vs 89.1%; HR 0.93; 95% CI 0.78-1.11). It is important to note that there was a 3.3% absolute improvement in 12-year OS with exemestane plus OFS among patients with HER2-negative tumors who received chemotherapy. This OS benefit was also noted amongst patients with high-risk clinicopathologic characteristics (<35 years and those with > 2 cm or grade 3 tumors), ranging from 4.0% to 5.5% absolute improvement. In conclusion, sustained recurrence risk reductions were noted with adjuvant exemestane plus OFS compared with tamoxifen plus OFS, with the most clinically meaningful survival benefit noted for patients with higher risk tumors. Proper selection of patients who are most likely to benefit from exemestane over tamoxifen is vital to maximize the survival benefit while minimizing the burden of treatment intensification.

Findings from a retrospective study including 221 women with BC who received preoperative neoadjuvant chemotherapy (NAC) showed that the presence of metabolic syndrome (MetS) worsened survival outcomes and increased disease recurrence risk (Zhou et al). Patients were divided into MetS and non-MetS groups according to National Cholesterol Education Program Adult Treatment Panel III criteria to investigate the association between MetS and clinicopathologic characteristics, pathologic complete response (pCR), and long-term survival. The MetS group had a significantly lower likelihood of achieving pCR after NAC compared with the non-MetS group (odds ratio [OR] 0.316; P = .028), with the risk for death (OR 2.587; P = .004) and disease recurrence (OR 2.228; P = .007) being significantly higher in patients with vs without MetS. In a multivariate analysis, MetS (P = 0.028) and hormone receptors status were independent predictors of pCR after NAC in BC. These findings emphasize the importance of timely intervention of metabolic syndrome to improve outcomes in patients with BC.