Commentary: New Research on BC Chemotherapies, March 2024

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Dr Roesch scans the journals so you don't have to!

Erin Roesch, MD
Adjuvant endocrine therapy with aromatase inhibitors (AI) significantly reduces risk for recurrence and favorably affects survival outcomes in early breast cancer (EBC). However, these therapies also carry potential side effects due to estrogen depletion, including increased bone resorption, decreased bone mineral density, and subsequently an increased risk for fracture. Bone-strengthening agents can help mitigate the risk for AI-related bone loss. Studies have demonstrated a benefit in terms of breast cancer outcomes with their use in the adjuvant setting.[1] A prospective, single-center cohort study that included 237 postmenopausal patients with hormone receptor–positive EBC who were receiving adjuvant AI treatment and denosumab every 6 months explored the association between risk factors for bone fracture and vertebral fracture progression in this population (Cosentini et al). After 18 months of treatment, a total of 4.4% of patients were noted to have vertebral fracture progression. Both Fracture Risk Assessment Tool (FRAX) score (odds ratio [OR] 3.95; 95% CI 1.09-14.39; P = .04) and percentage of fat body mass  (OR 5.41; 95% CI 1.49-19.59; P = .01) were independent variables associated with vertebral fracture progression. The relationship between obesity and bone density is complex; higher estrogen levels derived from adipose tissue exert a protective effect on bone mineral density, whereas inflammatory cytokines and other hormones can adversely affect bone quality.[2] This study highlights the beneficial role of modalities such as diet and exercise to achieve healthy body mass, and how these can work in conjunction with antiresorptive therapy (such as denosumab) to benefit bone health in women receiving AI.

The phase 3 KEYNOTE-355 trial established the role of chemotherapy in combination with pembrolizumab in the first-line setting for programmed death-ligand 1 (PD-L1)–positive advanced triple-negative breast cancer (TNBC). Patients unselected for PD-L1 status in this trial who received platinum- or taxane-based chemotherapy with placebo had a median progression-free survival of 5.6 months.[3] Strategies to improve upon efficacy and tolerability are desired in this space, and various trials have evaluated "switch maintenance" that involves receipt of an intensive induction regimen followed by a switch to an alternative/more tolerable regimen after response is achieved.[4] The phase II DORA trial randomized 45 patients with advanced TNBC and ongoing stable disease or complete or partial response from first- or second-line platinum-based chemotherapy to a maintenance regimen of olaparib (300 mg orally twice daily) with or without durvalumab (1500 mg on day 1 and every 4 weeks) (Tan et al). At a median follow-up of 9.8 months, median progression-free survival was 4.0 months (95% CI 2.6-6.1) with olaparib and 6.1 months (95% CI 3.7-10.1) with the combination; both were significantly longer than the historical control of continued platinum-based therapy (P = .0023 and P < .0001, respectively). Durable disease control appeared more pronounced in patients with complete or partial response to prior platinum therapy, and no new safety signals were observed. Future efforts to study this approach include the phase 2/3 KEYLYNK-009 trial, which is evaluating olaparib plus pembrolizumab maintenance therapy after first-line chemotherapy plus pembrolizumab for TNBC.[5]

TNBC is a heterogenous subtype, characterized by aggressive biology, and it benefits from chemotherapy and immunotherapy treatment approaches. Presently, the management of early-stage TNBC often involves neoadjuvant systemic therapy; however, a proportion of patients receive treatment in the postoperative setting, highlighting the relevance of time to initiation of adjuvant therapy as well.[6] Various prior studies have showed that delayed administration of adjuvant chemotherapy for EBC can lead to adverse survival outcomes. Furthermore, this effect is subtype-dependent, with more aggressive tumors (luminal B, triple-negative, human epidermal growth factor receptor 2 [HER2]-positive) exhibiting inferior outcomes with delayed chemotherapy.[7] A retrospective cohort study that included 245 patients with early TNBC who received adjuvant chemotherapy after surgery evaluated the impact of time to initiation of adjuvant therapy in this population (Hatzipanagiotou et al). Superior survival outcomes were observed for the group receiving systemic therapy 22-28 days after surgery (median overall survival 10.2 years) compared with those receiving adjuvant chemotherapy at later time points (29-35 days, 36-42 days, and >6 weeks after surgery; median overall survival 8.3 years, 7.8 years, and 6.9 years, respectively). Patients receiving chemotherapy 22-28 days after surgery had significantly better survival than those receiving chemotherapy 29-35 days (P = .043) and >6 weeks (P = 0.033) postoperatively. This study emphasizes the importance of timely administration of adjuvant chemotherapy for early TNBC, and efforts aimed to identify potential challenges and propose solutions to optimize outcomes in this space are valuable.

Additional References

  1. Gnant M, Frantal S, Pfeiler G, et al, for the Austrian Breast & Colorectal Cancer Study Group. Long-term outcomes of adjuvant denosumab in breast cancer. NEJM Evid. 2022;1:EVIDoa2200162. doi: 10.1056/EVIDoa2200162 Source
  2. Fassio A, Idolazzi L, Rossini M, et al. The obesity paradox and osteoporosis. Eating and Weight Disorders - Studies on Anorexia, Bulimia and Obesity. 2018;23:293-30 doi: 10.1007/s40519-018-0505-2 Source
  3. Cortes J, Cescon DW, Rugo HS, et al, for the KEYNOTE-355 Investigators. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): A randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet. 2020;396:1817-1828. doi: 10.1016/S0140-6736(20)32531-9 Source
  4. Bachelot T, Filleron T, Bieche I, et al. Durvalumab compared to maintenance chemotherapy in metastatic breast cancer: The randomized phase II SAFIR02-BREAST IMMUNO trial. Nat Med. 2021;27:250-255. doi: 10.1038/s41591-020-01189-2 Source
  5. Saji S, Cussac AL, Andre F, et al. 68TiP KEYLYNK-009: a phase II/III, open-label, randomized study of pembrolizumab (pembro) + olaparib (ola) vs pembro + chemotherapy after induction with first-line (1L) pembro + chemo in patients (pts) with locally recurrent inoperable or metastatic TNBC (abstract). Ann Oncol. 2020;31(Suppl 6):S1268. doi: 10.1016/j.annonc.2020.10.088 Source
  6. Ortmann O, Blohmer JU, Sibert NT, et al for 55 breast cancer centers certified by the German Cancer Society. Current clinical practice and outcome of neoadjuvant chemotherapy for early breast cancer: Analysis of individual data from 94,638 patients treated in 55 breast cancer centers. J Cancer Res Clin Oncol. 2023;149:1195-1209. doi: 10.1007/s00432-022-03938-x Source
  7. Yu KD, Fan L, Qiu LX, et al. Influence of delayed initiation of adjuvant chemotherapy on breast cancer survival is subtype-dependent. Oncotarget. 2017;8:46549-46556. doi: 10.18632/oncotarget.10551 Source
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Erin E. Roesch, MD, has disclosed the following relevant financial relationships: Serve(d) as a speaker or a member of a speakers bureau for: Puma Biotechnology

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Dr Roesch scans the journals so you don't have to!
Dr Roesch scans the journals so you don't have to!

Erin Roesch, MD
Adjuvant endocrine therapy with aromatase inhibitors (AI) significantly reduces risk for recurrence and favorably affects survival outcomes in early breast cancer (EBC). However, these therapies also carry potential side effects due to estrogen depletion, including increased bone resorption, decreased bone mineral density, and subsequently an increased risk for fracture. Bone-strengthening agents can help mitigate the risk for AI-related bone loss. Studies have demonstrated a benefit in terms of breast cancer outcomes with their use in the adjuvant setting.[1] A prospective, single-center cohort study that included 237 postmenopausal patients with hormone receptor–positive EBC who were receiving adjuvant AI treatment and denosumab every 6 months explored the association between risk factors for bone fracture and vertebral fracture progression in this population (Cosentini et al). After 18 months of treatment, a total of 4.4% of patients were noted to have vertebral fracture progression. Both Fracture Risk Assessment Tool (FRAX) score (odds ratio [OR] 3.95; 95% CI 1.09-14.39; P = .04) and percentage of fat body mass  (OR 5.41; 95% CI 1.49-19.59; P = .01) were independent variables associated with vertebral fracture progression. The relationship between obesity and bone density is complex; higher estrogen levels derived from adipose tissue exert a protective effect on bone mineral density, whereas inflammatory cytokines and other hormones can adversely affect bone quality.[2] This study highlights the beneficial role of modalities such as diet and exercise to achieve healthy body mass, and how these can work in conjunction with antiresorptive therapy (such as denosumab) to benefit bone health in women receiving AI.

The phase 3 KEYNOTE-355 trial established the role of chemotherapy in combination with pembrolizumab in the first-line setting for programmed death-ligand 1 (PD-L1)–positive advanced triple-negative breast cancer (TNBC). Patients unselected for PD-L1 status in this trial who received platinum- or taxane-based chemotherapy with placebo had a median progression-free survival of 5.6 months.[3] Strategies to improve upon efficacy and tolerability are desired in this space, and various trials have evaluated "switch maintenance" that involves receipt of an intensive induction regimen followed by a switch to an alternative/more tolerable regimen after response is achieved.[4] The phase II DORA trial randomized 45 patients with advanced TNBC and ongoing stable disease or complete or partial response from first- or second-line platinum-based chemotherapy to a maintenance regimen of olaparib (300 mg orally twice daily) with or without durvalumab (1500 mg on day 1 and every 4 weeks) (Tan et al). At a median follow-up of 9.8 months, median progression-free survival was 4.0 months (95% CI 2.6-6.1) with olaparib and 6.1 months (95% CI 3.7-10.1) with the combination; both were significantly longer than the historical control of continued platinum-based therapy (P = .0023 and P < .0001, respectively). Durable disease control appeared more pronounced in patients with complete or partial response to prior platinum therapy, and no new safety signals were observed. Future efforts to study this approach include the phase 2/3 KEYLYNK-009 trial, which is evaluating olaparib plus pembrolizumab maintenance therapy after first-line chemotherapy plus pembrolizumab for TNBC.[5]

TNBC is a heterogenous subtype, characterized by aggressive biology, and it benefits from chemotherapy and immunotherapy treatment approaches. Presently, the management of early-stage TNBC often involves neoadjuvant systemic therapy; however, a proportion of patients receive treatment in the postoperative setting, highlighting the relevance of time to initiation of adjuvant therapy as well.[6] Various prior studies have showed that delayed administration of adjuvant chemotherapy for EBC can lead to adverse survival outcomes. Furthermore, this effect is subtype-dependent, with more aggressive tumors (luminal B, triple-negative, human epidermal growth factor receptor 2 [HER2]-positive) exhibiting inferior outcomes with delayed chemotherapy.[7] A retrospective cohort study that included 245 patients with early TNBC who received adjuvant chemotherapy after surgery evaluated the impact of time to initiation of adjuvant therapy in this population (Hatzipanagiotou et al). Superior survival outcomes were observed for the group receiving systemic therapy 22-28 days after surgery (median overall survival 10.2 years) compared with those receiving adjuvant chemotherapy at later time points (29-35 days, 36-42 days, and >6 weeks after surgery; median overall survival 8.3 years, 7.8 years, and 6.9 years, respectively). Patients receiving chemotherapy 22-28 days after surgery had significantly better survival than those receiving chemotherapy 29-35 days (P = .043) and >6 weeks (P = 0.033) postoperatively. This study emphasizes the importance of timely administration of adjuvant chemotherapy for early TNBC, and efforts aimed to identify potential challenges and propose solutions to optimize outcomes in this space are valuable.

Additional References

  1. Gnant M, Frantal S, Pfeiler G, et al, for the Austrian Breast & Colorectal Cancer Study Group. Long-term outcomes of adjuvant denosumab in breast cancer. NEJM Evid. 2022;1:EVIDoa2200162. doi: 10.1056/EVIDoa2200162 Source
  2. Fassio A, Idolazzi L, Rossini M, et al. The obesity paradox and osteoporosis. Eating and Weight Disorders - Studies on Anorexia, Bulimia and Obesity. 2018;23:293-30 doi: 10.1007/s40519-018-0505-2 Source
  3. Cortes J, Cescon DW, Rugo HS, et al, for the KEYNOTE-355 Investigators. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): A randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet. 2020;396:1817-1828. doi: 10.1016/S0140-6736(20)32531-9 Source
  4. Bachelot T, Filleron T, Bieche I, et al. Durvalumab compared to maintenance chemotherapy in metastatic breast cancer: The randomized phase II SAFIR02-BREAST IMMUNO trial. Nat Med. 2021;27:250-255. doi: 10.1038/s41591-020-01189-2 Source
  5. Saji S, Cussac AL, Andre F, et al. 68TiP KEYLYNK-009: a phase II/III, open-label, randomized study of pembrolizumab (pembro) + olaparib (ola) vs pembro + chemotherapy after induction with first-line (1L) pembro + chemo in patients (pts) with locally recurrent inoperable or metastatic TNBC (abstract). Ann Oncol. 2020;31(Suppl 6):S1268. doi: 10.1016/j.annonc.2020.10.088 Source
  6. Ortmann O, Blohmer JU, Sibert NT, et al for 55 breast cancer centers certified by the German Cancer Society. Current clinical practice and outcome of neoadjuvant chemotherapy for early breast cancer: Analysis of individual data from 94,638 patients treated in 55 breast cancer centers. J Cancer Res Clin Oncol. 2023;149:1195-1209. doi: 10.1007/s00432-022-03938-x Source
  7. Yu KD, Fan L, Qiu LX, et al. Influence of delayed initiation of adjuvant chemotherapy on breast cancer survival is subtype-dependent. Oncotarget. 2017;8:46549-46556. doi: 10.18632/oncotarget.10551 Source

Erin Roesch, MD
Adjuvant endocrine therapy with aromatase inhibitors (AI) significantly reduces risk for recurrence and favorably affects survival outcomes in early breast cancer (EBC). However, these therapies also carry potential side effects due to estrogen depletion, including increased bone resorption, decreased bone mineral density, and subsequently an increased risk for fracture. Bone-strengthening agents can help mitigate the risk for AI-related bone loss. Studies have demonstrated a benefit in terms of breast cancer outcomes with their use in the adjuvant setting.[1] A prospective, single-center cohort study that included 237 postmenopausal patients with hormone receptor–positive EBC who were receiving adjuvant AI treatment and denosumab every 6 months explored the association between risk factors for bone fracture and vertebral fracture progression in this population (Cosentini et al). After 18 months of treatment, a total of 4.4% of patients were noted to have vertebral fracture progression. Both Fracture Risk Assessment Tool (FRAX) score (odds ratio [OR] 3.95; 95% CI 1.09-14.39; P = .04) and percentage of fat body mass  (OR 5.41; 95% CI 1.49-19.59; P = .01) were independent variables associated with vertebral fracture progression. The relationship between obesity and bone density is complex; higher estrogen levels derived from adipose tissue exert a protective effect on bone mineral density, whereas inflammatory cytokines and other hormones can adversely affect bone quality.[2] This study highlights the beneficial role of modalities such as diet and exercise to achieve healthy body mass, and how these can work in conjunction with antiresorptive therapy (such as denosumab) to benefit bone health in women receiving AI.

The phase 3 KEYNOTE-355 trial established the role of chemotherapy in combination with pembrolizumab in the first-line setting for programmed death-ligand 1 (PD-L1)–positive advanced triple-negative breast cancer (TNBC). Patients unselected for PD-L1 status in this trial who received platinum- or taxane-based chemotherapy with placebo had a median progression-free survival of 5.6 months.[3] Strategies to improve upon efficacy and tolerability are desired in this space, and various trials have evaluated "switch maintenance" that involves receipt of an intensive induction regimen followed by a switch to an alternative/more tolerable regimen after response is achieved.[4] The phase II DORA trial randomized 45 patients with advanced TNBC and ongoing stable disease or complete or partial response from first- or second-line platinum-based chemotherapy to a maintenance regimen of olaparib (300 mg orally twice daily) with or without durvalumab (1500 mg on day 1 and every 4 weeks) (Tan et al). At a median follow-up of 9.8 months, median progression-free survival was 4.0 months (95% CI 2.6-6.1) with olaparib and 6.1 months (95% CI 3.7-10.1) with the combination; both were significantly longer than the historical control of continued platinum-based therapy (P = .0023 and P < .0001, respectively). Durable disease control appeared more pronounced in patients with complete or partial response to prior platinum therapy, and no new safety signals were observed. Future efforts to study this approach include the phase 2/3 KEYLYNK-009 trial, which is evaluating olaparib plus pembrolizumab maintenance therapy after first-line chemotherapy plus pembrolizumab for TNBC.[5]

TNBC is a heterogenous subtype, characterized by aggressive biology, and it benefits from chemotherapy and immunotherapy treatment approaches. Presently, the management of early-stage TNBC often involves neoadjuvant systemic therapy; however, a proportion of patients receive treatment in the postoperative setting, highlighting the relevance of time to initiation of adjuvant therapy as well.[6] Various prior studies have showed that delayed administration of adjuvant chemotherapy for EBC can lead to adverse survival outcomes. Furthermore, this effect is subtype-dependent, with more aggressive tumors (luminal B, triple-negative, human epidermal growth factor receptor 2 [HER2]-positive) exhibiting inferior outcomes with delayed chemotherapy.[7] A retrospective cohort study that included 245 patients with early TNBC who received adjuvant chemotherapy after surgery evaluated the impact of time to initiation of adjuvant therapy in this population (Hatzipanagiotou et al). Superior survival outcomes were observed for the group receiving systemic therapy 22-28 days after surgery (median overall survival 10.2 years) compared with those receiving adjuvant chemotherapy at later time points (29-35 days, 36-42 days, and >6 weeks after surgery; median overall survival 8.3 years, 7.8 years, and 6.9 years, respectively). Patients receiving chemotherapy 22-28 days after surgery had significantly better survival than those receiving chemotherapy 29-35 days (P = .043) and >6 weeks (P = 0.033) postoperatively. This study emphasizes the importance of timely administration of adjuvant chemotherapy for early TNBC, and efforts aimed to identify potential challenges and propose solutions to optimize outcomes in this space are valuable.

Additional References

  1. Gnant M, Frantal S, Pfeiler G, et al, for the Austrian Breast & Colorectal Cancer Study Group. Long-term outcomes of adjuvant denosumab in breast cancer. NEJM Evid. 2022;1:EVIDoa2200162. doi: 10.1056/EVIDoa2200162 Source
  2. Fassio A, Idolazzi L, Rossini M, et al. The obesity paradox and osteoporosis. Eating and Weight Disorders - Studies on Anorexia, Bulimia and Obesity. 2018;23:293-30 doi: 10.1007/s40519-018-0505-2 Source
  3. Cortes J, Cescon DW, Rugo HS, et al, for the KEYNOTE-355 Investigators. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): A randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet. 2020;396:1817-1828. doi: 10.1016/S0140-6736(20)32531-9 Source
  4. Bachelot T, Filleron T, Bieche I, et al. Durvalumab compared to maintenance chemotherapy in metastatic breast cancer: The randomized phase II SAFIR02-BREAST IMMUNO trial. Nat Med. 2021;27:250-255. doi: 10.1038/s41591-020-01189-2 Source
  5. Saji S, Cussac AL, Andre F, et al. 68TiP KEYLYNK-009: a phase II/III, open-label, randomized study of pembrolizumab (pembro) + olaparib (ola) vs pembro + chemotherapy after induction with first-line (1L) pembro + chemo in patients (pts) with locally recurrent inoperable or metastatic TNBC (abstract). Ann Oncol. 2020;31(Suppl 6):S1268. doi: 10.1016/j.annonc.2020.10.088 Source
  6. Ortmann O, Blohmer JU, Sibert NT, et al for 55 breast cancer centers certified by the German Cancer Society. Current clinical practice and outcome of neoadjuvant chemotherapy for early breast cancer: Analysis of individual data from 94,638 patients treated in 55 breast cancer centers. J Cancer Res Clin Oncol. 2023;149:1195-1209. doi: 10.1007/s00432-022-03938-x Source
  7. Yu KD, Fan L, Qiu LX, et al. Influence of delayed initiation of adjuvant chemotherapy on breast cancer survival is subtype-dependent. Oncotarget. 2017;8:46549-46556. doi: 10.18632/oncotarget.10551 Source
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Commentary: Medication Timing and Other Dupilumab Concerns, March 2024

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Dr. Feldman scans the journals, so you don’t have to!

Steven R. Feldman, MD, PhD
Ahn and colleagues found that having atopic dermatitis (AD) is associated with a higher risk for subsequent autoimmune disease. Is it a significant increased risk? What do we mean by "significant"? If we mean that the difference they observed wasn't likely due to chance alone, then yes, the observed difference was significant in the sense of being statistically significant. But what we really want to know is whether the difference they saw was large enough that someone with AD should lose sleep over it; I don't think they should. About six in 1000 patients per year without AD had a subsequent autoimmune disease; about eight in 1000 patients per year with AD had a subsequent autoimmune disease. There may be some genetic propensity to autoimmune disease in people with AD, but the great majority of people with AD, like the great majority of people in general, will not develop a subsequent autoimmune disease.

When skin diseases affect the palm or sole, they can have a disproportionately large negative effect on patients' lives. Hand and foot dermatitis can be disabling. Simpson and colleagues find that dupilumab is an effective treatment for AD of the hands and feet. Having safe and effective treatment for hand and foot dermatitis will be life-changing for many of our patients.

Patients often do very well with biologic treatment. When they do, they often wonder, Do I need to continue taking the medication? Lasheras-Pérez and colleagues found that the great majority of patients doing well taking dupilumab for AD could stretch out their dosing interval. I suspect a lot of our patients are doing this already. I used to worry that stretching out the dosing interval might lead to antidrug antibodies and loss of activity. Such loss of activity doesn't appear common. Because we also have multiple alternative treatments for severe AD, I think it may be quite reasonable for patients to try spreading out their doses after their disease has been well controlled for a good long time.

Superficial skin infections aren't rare in children, particularly children with AD. Paller and colleagues' study is informative about the safety of dupilumab in children. The drug, which blocks a pathway of the immune system, was associated with fewer infections. This is good news. The reduction in infections could be through restoring "immune balance" (whatever that means) or by improving skin barrier function. Perhaps the low rate of infection explains why dupilumab is not considered immunosuppressive.

I love studies of drug survival because I think that knowing the percentage of patients who stay with drug treatment is a good measure of overall safety and efficacy. Pezzolo and colleagues found — perhaps not surprisingly given the extraordinary efficacy of upadacitinib for AD — that almost no one discontinued the drug over 1.5 years due to lack of efficacy. There were patients who discontinued due to adverse events (and additional patients lost to follow-up who perhaps also discontinued the drug), but 80% of patients were still in the study at the end of 1.5 years. Three patients who weren't vaccinated for shingles developed shingles; encouraging patients to get the shingles vaccine may be a prudent measure when starting patients taking upadacitinib. 
 

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Professor of Dermatology, Pathology and Social Sciences & Health Policy Wake Forest University School of Medicine, Winston-Salem, NC

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Dr. Feldman scans the journals, so you don’t have to!
Dr. Feldman scans the journals, so you don’t have to!

Steven R. Feldman, MD, PhD
Ahn and colleagues found that having atopic dermatitis (AD) is associated with a higher risk for subsequent autoimmune disease. Is it a significant increased risk? What do we mean by "significant"? If we mean that the difference they observed wasn't likely due to chance alone, then yes, the observed difference was significant in the sense of being statistically significant. But what we really want to know is whether the difference they saw was large enough that someone with AD should lose sleep over it; I don't think they should. About six in 1000 patients per year without AD had a subsequent autoimmune disease; about eight in 1000 patients per year with AD had a subsequent autoimmune disease. There may be some genetic propensity to autoimmune disease in people with AD, but the great majority of people with AD, like the great majority of people in general, will not develop a subsequent autoimmune disease.

When skin diseases affect the palm or sole, they can have a disproportionately large negative effect on patients' lives. Hand and foot dermatitis can be disabling. Simpson and colleagues find that dupilumab is an effective treatment for AD of the hands and feet. Having safe and effective treatment for hand and foot dermatitis will be life-changing for many of our patients.

Patients often do very well with biologic treatment. When they do, they often wonder, Do I need to continue taking the medication? Lasheras-Pérez and colleagues found that the great majority of patients doing well taking dupilumab for AD could stretch out their dosing interval. I suspect a lot of our patients are doing this already. I used to worry that stretching out the dosing interval might lead to antidrug antibodies and loss of activity. Such loss of activity doesn't appear common. Because we also have multiple alternative treatments for severe AD, I think it may be quite reasonable for patients to try spreading out their doses after their disease has been well controlled for a good long time.

Superficial skin infections aren't rare in children, particularly children with AD. Paller and colleagues' study is informative about the safety of dupilumab in children. The drug, which blocks a pathway of the immune system, was associated with fewer infections. This is good news. The reduction in infections could be through restoring "immune balance" (whatever that means) or by improving skin barrier function. Perhaps the low rate of infection explains why dupilumab is not considered immunosuppressive.

I love studies of drug survival because I think that knowing the percentage of patients who stay with drug treatment is a good measure of overall safety and efficacy. Pezzolo and colleagues found — perhaps not surprisingly given the extraordinary efficacy of upadacitinib for AD — that almost no one discontinued the drug over 1.5 years due to lack of efficacy. There were patients who discontinued due to adverse events (and additional patients lost to follow-up who perhaps also discontinued the drug), but 80% of patients were still in the study at the end of 1.5 years. Three patients who weren't vaccinated for shingles developed shingles; encouraging patients to get the shingles vaccine may be a prudent measure when starting patients taking upadacitinib. 
 

Steven R. Feldman, MD, PhD
Ahn and colleagues found that having atopic dermatitis (AD) is associated with a higher risk for subsequent autoimmune disease. Is it a significant increased risk? What do we mean by "significant"? If we mean that the difference they observed wasn't likely due to chance alone, then yes, the observed difference was significant in the sense of being statistically significant. But what we really want to know is whether the difference they saw was large enough that someone with AD should lose sleep over it; I don't think they should. About six in 1000 patients per year without AD had a subsequent autoimmune disease; about eight in 1000 patients per year with AD had a subsequent autoimmune disease. There may be some genetic propensity to autoimmune disease in people with AD, but the great majority of people with AD, like the great majority of people in general, will not develop a subsequent autoimmune disease.

When skin diseases affect the palm or sole, they can have a disproportionately large negative effect on patients' lives. Hand and foot dermatitis can be disabling. Simpson and colleagues find that dupilumab is an effective treatment for AD of the hands and feet. Having safe and effective treatment for hand and foot dermatitis will be life-changing for many of our patients.

Patients often do very well with biologic treatment. When they do, they often wonder, Do I need to continue taking the medication? Lasheras-Pérez and colleagues found that the great majority of patients doing well taking dupilumab for AD could stretch out their dosing interval. I suspect a lot of our patients are doing this already. I used to worry that stretching out the dosing interval might lead to antidrug antibodies and loss of activity. Such loss of activity doesn't appear common. Because we also have multiple alternative treatments for severe AD, I think it may be quite reasonable for patients to try spreading out their doses after their disease has been well controlled for a good long time.

Superficial skin infections aren't rare in children, particularly children with AD. Paller and colleagues' study is informative about the safety of dupilumab in children. The drug, which blocks a pathway of the immune system, was associated with fewer infections. This is good news. The reduction in infections could be through restoring "immune balance" (whatever that means) or by improving skin barrier function. Perhaps the low rate of infection explains why dupilumab is not considered immunosuppressive.

I love studies of drug survival because I think that knowing the percentage of patients who stay with drug treatment is a good measure of overall safety and efficacy. Pezzolo and colleagues found — perhaps not surprisingly given the extraordinary efficacy of upadacitinib for AD — that almost no one discontinued the drug over 1.5 years due to lack of efficacy. There were patients who discontinued due to adverse events (and additional patients lost to follow-up who perhaps also discontinued the drug), but 80% of patients were still in the study at the end of 1.5 years. Three patients who weren't vaccinated for shingles developed shingles; encouraging patients to get the shingles vaccine may be a prudent measure when starting patients taking upadacitinib. 
 

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Clinical Edge Journal Scan
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RINVOQ [ 5260 ]

Comparative Efficacy of Lasmiditan and Calcitonin Gene-Related Peptide-Antagonists for Migraine

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Key clinical point: Calcitonin gene-related peptide-antagonists, such as rimegepant and Ubrogepant, can be used for treating acute migraine due to their favorable efficacy and safety, whereas lasmiditan, despite showing promising efficacy, may increase the risk for adverse events (AE).

Major finding: Compared with other drugs, 100 mg ubrogepant showed the highest surface under the cumulative ranking curve (SUCRA) for providing quick pain freedom at 2 hours (0.79) and sustained pain freedom for over 24 hours (0.74), and 75 mg rimegepant showed the highest SUCRA for providing freedom from photophobia within 2 hours (0.96). Although both 100 mg and 200 mg lasmiditan provided relief from headache pain at 2 hours, they increased the risk for AE.

Study details: Findings are from a network meta-analysis of 18 studies including 22,429 patients with migraine who received lasmiditan, rimegepant, ubrogepant, and zavegepant.

Disclosures: This study was supported by the Fundamental Research Funds for the Central Universities, China. The authors declared no conflicts of interest.

Source: Deng X, Zhou L, Liang C et al. Comparison of effectiveness and safety of lasmiditan and CGRP-antagonists for the acute treatment of migraine in adults: Systematic review and network meta-analysis of randomised trials. J Headache Pain. 2024;25:16. doi: 10.1186/s10194-024-01723-4 Source

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Key clinical point: Calcitonin gene-related peptide-antagonists, such as rimegepant and Ubrogepant, can be used for treating acute migraine due to their favorable efficacy and safety, whereas lasmiditan, despite showing promising efficacy, may increase the risk for adverse events (AE).

Major finding: Compared with other drugs, 100 mg ubrogepant showed the highest surface under the cumulative ranking curve (SUCRA) for providing quick pain freedom at 2 hours (0.79) and sustained pain freedom for over 24 hours (0.74), and 75 mg rimegepant showed the highest SUCRA for providing freedom from photophobia within 2 hours (0.96). Although both 100 mg and 200 mg lasmiditan provided relief from headache pain at 2 hours, they increased the risk for AE.

Study details: Findings are from a network meta-analysis of 18 studies including 22,429 patients with migraine who received lasmiditan, rimegepant, ubrogepant, and zavegepant.

Disclosures: This study was supported by the Fundamental Research Funds for the Central Universities, China. The authors declared no conflicts of interest.

Source: Deng X, Zhou L, Liang C et al. Comparison of effectiveness and safety of lasmiditan and CGRP-antagonists for the acute treatment of migraine in adults: Systematic review and network meta-analysis of randomised trials. J Headache Pain. 2024;25:16. doi: 10.1186/s10194-024-01723-4 Source

Key clinical point: Calcitonin gene-related peptide-antagonists, such as rimegepant and Ubrogepant, can be used for treating acute migraine due to their favorable efficacy and safety, whereas lasmiditan, despite showing promising efficacy, may increase the risk for adverse events (AE).

Major finding: Compared with other drugs, 100 mg ubrogepant showed the highest surface under the cumulative ranking curve (SUCRA) for providing quick pain freedom at 2 hours (0.79) and sustained pain freedom for over 24 hours (0.74), and 75 mg rimegepant showed the highest SUCRA for providing freedom from photophobia within 2 hours (0.96). Although both 100 mg and 200 mg lasmiditan provided relief from headache pain at 2 hours, they increased the risk for AE.

Study details: Findings are from a network meta-analysis of 18 studies including 22,429 patients with migraine who received lasmiditan, rimegepant, ubrogepant, and zavegepant.

Disclosures: This study was supported by the Fundamental Research Funds for the Central Universities, China. The authors declared no conflicts of interest.

Source: Deng X, Zhou L, Liang C et al. Comparison of effectiveness and safety of lasmiditan and CGRP-antagonists for the acute treatment of migraine in adults: Systematic review and network meta-analysis of randomised trials. J Headache Pain. 2024;25:16. doi: 10.1186/s10194-024-01723-4 Source

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Habitual Intake of Caffeinated Beverages May Not Trigger Headache in Episodic Migraine

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Key clinical point: Habitual intake of caffeinated beverages may not increase headache frequency, duration, or intensity in patients with episodic migraine, contrary to popular belief.

Major finding: Compared with patients having episodic migraine who did not habitually consume caffeinated beverages, those who consumed 1-2 servings per day reported 0.3 (95% CI −2.0 to 2.5) more headache days per month, whereas those who consumed 3-4 servings per day reported 1.3 (95% CI −4.5 to 1.9) fewer headache days per month. Moreover, the headache duration and intensity did not differ across levels of caffeinated beverage intake.

Study details: This prospective cohort study evaluated the association between habitual caffeinated beverages intake and headache outcomes among 97 patients with episodic migraine (age 18 years).

Disclosures: This study was funded by US National Institute of Neurological Disorders and Stroke, the American Sleep Medicine Foundation, Harvard Catalyst—The Harvard Clinical and Translational Science Center. Suzanne M. Bertisch declared serving as a consultant for Idorsia and ResMed. The other authors declared no conflicts of interest.

Source: Mittleman MR, Mostofsky E, Vgontzas A, Bertisch SM. Habitual caffeinated beverage consumption and headaches among adults with episodic migraine: A prospective cohort study. Headache. 2024 (Feb 6). doi: 10.1111/head.14673 Source

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Key clinical point: Habitual intake of caffeinated beverages may not increase headache frequency, duration, or intensity in patients with episodic migraine, contrary to popular belief.

Major finding: Compared with patients having episodic migraine who did not habitually consume caffeinated beverages, those who consumed 1-2 servings per day reported 0.3 (95% CI −2.0 to 2.5) more headache days per month, whereas those who consumed 3-4 servings per day reported 1.3 (95% CI −4.5 to 1.9) fewer headache days per month. Moreover, the headache duration and intensity did not differ across levels of caffeinated beverage intake.

Study details: This prospective cohort study evaluated the association between habitual caffeinated beverages intake and headache outcomes among 97 patients with episodic migraine (age 18 years).

Disclosures: This study was funded by US National Institute of Neurological Disorders and Stroke, the American Sleep Medicine Foundation, Harvard Catalyst—The Harvard Clinical and Translational Science Center. Suzanne M. Bertisch declared serving as a consultant for Idorsia and ResMed. The other authors declared no conflicts of interest.

Source: Mittleman MR, Mostofsky E, Vgontzas A, Bertisch SM. Habitual caffeinated beverage consumption and headaches among adults with episodic migraine: A prospective cohort study. Headache. 2024 (Feb 6). doi: 10.1111/head.14673 Source

Key clinical point: Habitual intake of caffeinated beverages may not increase headache frequency, duration, or intensity in patients with episodic migraine, contrary to popular belief.

Major finding: Compared with patients having episodic migraine who did not habitually consume caffeinated beverages, those who consumed 1-2 servings per day reported 0.3 (95% CI −2.0 to 2.5) more headache days per month, whereas those who consumed 3-4 servings per day reported 1.3 (95% CI −4.5 to 1.9) fewer headache days per month. Moreover, the headache duration and intensity did not differ across levels of caffeinated beverage intake.

Study details: This prospective cohort study evaluated the association between habitual caffeinated beverages intake and headache outcomes among 97 patients with episodic migraine (age 18 years).

Disclosures: This study was funded by US National Institute of Neurological Disorders and Stroke, the American Sleep Medicine Foundation, Harvard Catalyst—The Harvard Clinical and Translational Science Center. Suzanne M. Bertisch declared serving as a consultant for Idorsia and ResMed. The other authors declared no conflicts of interest.

Source: Mittleman MR, Mostofsky E, Vgontzas A, Bertisch SM. Habitual caffeinated beverage consumption and headaches among adults with episodic migraine: A prospective cohort study. Headache. 2024 (Feb 6). doi: 10.1111/head.14673 Source

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Comparing Real-World Efficacy of Anti-CGRP mAb vs OnabotulinumtoxinA

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Key clinical point: Anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb) were more effective than onabotulinumtoxinA (BoNT-A) in reducing monthly headache days (MHD) in patients with chronic migraine (CM), although the safety profile of both treatments was comparable.

Major finding: Anti-CGRP mAb vs BoNT-A led to a significantly greater reduction in MHD at 6 months (adjusted mean difference 7.1; P < .001) and 12 months(adjusted mean difference 6.2; P < .001). Both treatments had favorable and comparable safety profiles.

Study details: Findings are from an observational, retrospective, multicenter, cohort study including 183 patients with CM who had at least two oral preventive treatment failures and received anti-CGRP mAb (n = 86) and BoNT-A (n = 97).

Disclosures: This study was supported by Italian Ministry of Health. Four authors declared receiving consultancy and advisory fees, travel grants, honoraria, or personal fees for participating in advisory boards, speaker panels, or clinical investigation studies from various sources.

Source: Grazzi L, Giossi R, Montisano DA et al. Real-world effectiveness of anti-CGRP monoclonal antibodies compared to onabotulinumtoxinA (RAMO) in chronic migraine: A retrospective, observational, multicenter, cohort study. J Headache Pain. 2024;25:14. doi: 10.1186/s10194-024-01721-6 Source

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Key clinical point: Anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb) were more effective than onabotulinumtoxinA (BoNT-A) in reducing monthly headache days (MHD) in patients with chronic migraine (CM), although the safety profile of both treatments was comparable.

Major finding: Anti-CGRP mAb vs BoNT-A led to a significantly greater reduction in MHD at 6 months (adjusted mean difference 7.1; P < .001) and 12 months(adjusted mean difference 6.2; P < .001). Both treatments had favorable and comparable safety profiles.

Study details: Findings are from an observational, retrospective, multicenter, cohort study including 183 patients with CM who had at least two oral preventive treatment failures and received anti-CGRP mAb (n = 86) and BoNT-A (n = 97).

Disclosures: This study was supported by Italian Ministry of Health. Four authors declared receiving consultancy and advisory fees, travel grants, honoraria, or personal fees for participating in advisory boards, speaker panels, or clinical investigation studies from various sources.

Source: Grazzi L, Giossi R, Montisano DA et al. Real-world effectiveness of anti-CGRP monoclonal antibodies compared to onabotulinumtoxinA (RAMO) in chronic migraine: A retrospective, observational, multicenter, cohort study. J Headache Pain. 2024;25:14. doi: 10.1186/s10194-024-01721-6 Source

Key clinical point: Anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb) were more effective than onabotulinumtoxinA (BoNT-A) in reducing monthly headache days (MHD) in patients with chronic migraine (CM), although the safety profile of both treatments was comparable.

Major finding: Anti-CGRP mAb vs BoNT-A led to a significantly greater reduction in MHD at 6 months (adjusted mean difference 7.1; P < .001) and 12 months(adjusted mean difference 6.2; P < .001). Both treatments had favorable and comparable safety profiles.

Study details: Findings are from an observational, retrospective, multicenter, cohort study including 183 patients with CM who had at least two oral preventive treatment failures and received anti-CGRP mAb (n = 86) and BoNT-A (n = 97).

Disclosures: This study was supported by Italian Ministry of Health. Four authors declared receiving consultancy and advisory fees, travel grants, honoraria, or personal fees for participating in advisory boards, speaker panels, or clinical investigation studies from various sources.

Source: Grazzi L, Giossi R, Montisano DA et al. Real-world effectiveness of anti-CGRP monoclonal antibodies compared to onabotulinumtoxinA (RAMO) in chronic migraine: A retrospective, observational, multicenter, cohort study. J Headache Pain. 2024;25:14. doi: 10.1186/s10194-024-01721-6 Source

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Is There Any Link Between Allergic Rhinitis and Migraine?

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and migraine or its subtypes, and vice versa.

Major finding: Genetic predispositions to AR were not casually associated with a higher risk for migraine (odds ratio [OR] 0.816; P = .394), both with aura (OR 0.690; P = .384) and without aura (OR 1.022; P = .954). Reciprocally, genetic predispositions to migraine or its subtypes showed no casual association with AR.

Study details: This two-sample Mendelian randomization analysis included 25,486 patients with AR and 87,907 control individuals without AR along with 3541 patients with migraine with aura, 3215 patients with migraine without aura, and 176,107 controls individuals without migraine.

Disclosures: This study was supported by grants from the National Natural Science Foundation of China and the Fundamental Research Funds for the Central Universities. The authors declared no conflicts of interest.

Source: Lv H, Liu K, Xie Y et al. No causal association between allergic rhinitis and migraine: A Mendelian randomization study. Eur J Med Res. 2024;29:78. doi: 10.1186/s40001-024-01682-1 Source

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and migraine or its subtypes, and vice versa.

Major finding: Genetic predispositions to AR were not casually associated with a higher risk for migraine (odds ratio [OR] 0.816; P = .394), both with aura (OR 0.690; P = .384) and without aura (OR 1.022; P = .954). Reciprocally, genetic predispositions to migraine or its subtypes showed no casual association with AR.

Study details: This two-sample Mendelian randomization analysis included 25,486 patients with AR and 87,907 control individuals without AR along with 3541 patients with migraine with aura, 3215 patients with migraine without aura, and 176,107 controls individuals without migraine.

Disclosures: This study was supported by grants from the National Natural Science Foundation of China and the Fundamental Research Funds for the Central Universities. The authors declared no conflicts of interest.

Source: Lv H, Liu K, Xie Y et al. No causal association between allergic rhinitis and migraine: A Mendelian randomization study. Eur J Med Res. 2024;29:78. doi: 10.1186/s40001-024-01682-1 Source

and migraine or its subtypes, and vice versa.

Major finding: Genetic predispositions to AR were not casually associated with a higher risk for migraine (odds ratio [OR] 0.816; P = .394), both with aura (OR 0.690; P = .384) and without aura (OR 1.022; P = .954). Reciprocally, genetic predispositions to migraine or its subtypes showed no casual association with AR.

Study details: This two-sample Mendelian randomization analysis included 25,486 patients with AR and 87,907 control individuals without AR along with 3541 patients with migraine with aura, 3215 patients with migraine without aura, and 176,107 controls individuals without migraine.

Disclosures: This study was supported by grants from the National Natural Science Foundation of China and the Fundamental Research Funds for the Central Universities. The authors declared no conflicts of interest.

Source: Lv H, Liu K, Xie Y et al. No causal association between allergic rhinitis and migraine: A Mendelian randomization study. Eur J Med Res. 2024;29:78. doi: 10.1186/s40001-024-01682-1 Source

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Resuming Anti-CGRP Monoclonal Antibodies Effective for Migraine Prevention

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Key clinical point: Resuming anti-calcitonin gene-related peptide (anti-CGRP) monoclonal antibodies (mAb) therapy was beneficial in patients with migraine who had responded to this treatment previously but relapsed upon discontinuation.

Major finding: The median monthly headache days (MHD) improved from 16 in the month before antibody reintroduction to 8 after 3 months of treatment re-introduction. The majority of patients achieved 30% reduction in MHD (75.3%) and monthly migraine days (80.8%) during the second treatment period with anti-CGRP mAb.

Study details: This observational prospective analytical multicentric study included 360 patients with migraine who had shown prior response to anti-CGRP mAb, with clinical worsening after withdrawal and were re-introduced anti-CGRP mAb therapy.

Disclosures: This study was funded by the Instituto de Salud Carlos III, European Union, and  Fondo Europeo de Desarrollo Regional (FEDER) funds. Several authors declared receiving speaker honoraria, payments or honoraria for lectures, or research support or grants from various sources.

Source: Romero Del Rincón C, Gonzalez-Martinez A, Quintas S et al. RE-START: Exploring the effectiveness of anti-calcitonin gene-related peptide resumption after discontinuation in migraine. Eur J Neurol. 2024 (Jan 25). doi: 10.1111/ene.16203 Source

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Key clinical point: Resuming anti-calcitonin gene-related peptide (anti-CGRP) monoclonal antibodies (mAb) therapy was beneficial in patients with migraine who had responded to this treatment previously but relapsed upon discontinuation.

Major finding: The median monthly headache days (MHD) improved from 16 in the month before antibody reintroduction to 8 after 3 months of treatment re-introduction. The majority of patients achieved 30% reduction in MHD (75.3%) and monthly migraine days (80.8%) during the second treatment period with anti-CGRP mAb.

Study details: This observational prospective analytical multicentric study included 360 patients with migraine who had shown prior response to anti-CGRP mAb, with clinical worsening after withdrawal and were re-introduced anti-CGRP mAb therapy.

Disclosures: This study was funded by the Instituto de Salud Carlos III, European Union, and  Fondo Europeo de Desarrollo Regional (FEDER) funds. Several authors declared receiving speaker honoraria, payments or honoraria for lectures, or research support or grants from various sources.

Source: Romero Del Rincón C, Gonzalez-Martinez A, Quintas S et al. RE-START: Exploring the effectiveness of anti-calcitonin gene-related peptide resumption after discontinuation in migraine. Eur J Neurol. 2024 (Jan 25). doi: 10.1111/ene.16203 Source

Key clinical point: Resuming anti-calcitonin gene-related peptide (anti-CGRP) monoclonal antibodies (mAb) therapy was beneficial in patients with migraine who had responded to this treatment previously but relapsed upon discontinuation.

Major finding: The median monthly headache days (MHD) improved from 16 in the month before antibody reintroduction to 8 after 3 months of treatment re-introduction. The majority of patients achieved 30% reduction in MHD (75.3%) and monthly migraine days (80.8%) during the second treatment period with anti-CGRP mAb.

Study details: This observational prospective analytical multicentric study included 360 patients with migraine who had shown prior response to anti-CGRP mAb, with clinical worsening after withdrawal and were re-introduced anti-CGRP mAb therapy.

Disclosures: This study was funded by the Instituto de Salud Carlos III, European Union, and  Fondo Europeo de Desarrollo Regional (FEDER) funds. Several authors declared receiving speaker honoraria, payments or honoraria for lectures, or research support or grants from various sources.

Source: Romero Del Rincón C, Gonzalez-Martinez A, Quintas S et al. RE-START: Exploring the effectiveness of anti-calcitonin gene-related peptide resumption after discontinuation in migraine. Eur J Neurol. 2024 (Jan 25). doi: 10.1111/ene.16203 Source

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Presence of Diabetes May Worsen the Effects of BMI on Migraine

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Key clinical point: Body mass index (BMI) was positively correlated with an increased risk for severe headache or migraine, with the association being further increased in patients with diabetes and high BMI.

Major finding: BMI was positively associated with a higher risk for migraine (adjusted odds ratio [aOR] 1.02; P < .001), with participants in the highest (≥30.0 kg/m2) vs lowest (<25.0 kg/m2) BMI groups reporting an increased risk for migraine (aOR 1.30; P = .0022). The positive association between BMI and migraine was further strengthened in patients with diabetes, who had BMI ≥ 29.71 kg/m2 (aOR 1.30; P = . 003).

Study details: This cross-sectional study included 10,074 participants, of whom 2004 had migraine and 1020 had diabetes.

Disclosures: This work was supported by the National Natural Science Foundation of China and Jiangxi Province, Jiangxi Provincial Department of Education Science and Technology Program Project, and Jiangxi Province Postgraduate Innovation Special Fund. The authors declared no competing interests.

Source: Tian S, Cheng Z, Zheng H et al. Interaction between diabetes and body mass index on severe headache or migraine in adults: A cross-sectional study. BMC Geriatr. 2024;24:76. doi: 10.1186/s12877-024-04657-3 Source

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Key clinical point: Body mass index (BMI) was positively correlated with an increased risk for severe headache or migraine, with the association being further increased in patients with diabetes and high BMI.

Major finding: BMI was positively associated with a higher risk for migraine (adjusted odds ratio [aOR] 1.02; P < .001), with participants in the highest (≥30.0 kg/m2) vs lowest (<25.0 kg/m2) BMI groups reporting an increased risk for migraine (aOR 1.30; P = .0022). The positive association between BMI and migraine was further strengthened in patients with diabetes, who had BMI ≥ 29.71 kg/m2 (aOR 1.30; P = . 003).

Study details: This cross-sectional study included 10,074 participants, of whom 2004 had migraine and 1020 had diabetes.

Disclosures: This work was supported by the National Natural Science Foundation of China and Jiangxi Province, Jiangxi Provincial Department of Education Science and Technology Program Project, and Jiangxi Province Postgraduate Innovation Special Fund. The authors declared no competing interests.

Source: Tian S, Cheng Z, Zheng H et al. Interaction between diabetes and body mass index on severe headache or migraine in adults: A cross-sectional study. BMC Geriatr. 2024;24:76. doi: 10.1186/s12877-024-04657-3 Source

Key clinical point: Body mass index (BMI) was positively correlated with an increased risk for severe headache or migraine, with the association being further increased in patients with diabetes and high BMI.

Major finding: BMI was positively associated with a higher risk for migraine (adjusted odds ratio [aOR] 1.02; P < .001), with participants in the highest (≥30.0 kg/m2) vs lowest (<25.0 kg/m2) BMI groups reporting an increased risk for migraine (aOR 1.30; P = .0022). The positive association between BMI and migraine was further strengthened in patients with diabetes, who had BMI ≥ 29.71 kg/m2 (aOR 1.30; P = . 003).

Study details: This cross-sectional study included 10,074 participants, of whom 2004 had migraine and 1020 had diabetes.

Disclosures: This work was supported by the National Natural Science Foundation of China and Jiangxi Province, Jiangxi Provincial Department of Education Science and Technology Program Project, and Jiangxi Province Postgraduate Innovation Special Fund. The authors declared no competing interests.

Source: Tian S, Cheng Z, Zheng H et al. Interaction between diabetes and body mass index on severe headache or migraine in adults: A cross-sectional study. BMC Geriatr. 2024;24:76. doi: 10.1186/s12877-024-04657-3 Source

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Eptinezumab Effective in Migraine Regardless of Prior Treatment Failure Type

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Key clinical point: Eptinezumab vs placebo led to a greater reduction in migraine frequency and an improvement in migraine response in patients with migraine, irrespective of the type of prior treatment failure.

Major finding: Across weeks 1-12, patients receiving eptinezumab vs placebo experienced greater reductions in monthly migraine days (MMD) from baseline in all subgroups, with even greater improvements at weeks 13-24 (all P < .0001). Migraine responder rates (50% reduction in MMD) were also higher with eptinezumab vs placebo and increased following a second infusion (all P < .0001).

Study details: Findings are from a post hoc analysis of the DELIVER trial that included 890 patients with migraine who were randomly assigned to receive either 100 mg or 300 mg eptinezumab or placebo.

Disclosures: The study was sponsored and funded by H. Lundbeck A/S. Several authors declared receiving personal fees, research support, or research funding from various sources. Four authors declared being full-time employees of or holding stocks in Lundbeck or one of its subsidiary companies.

Source: Pozo-Rosich P, Ashina M, Tepper SJ et al. Eptinezumab demonstrated efficacy regardless of prior preventive migraine treatment failure type: Post hoc analyses of the DELIVER study. Neurol Ther. 2024 (Jan 18). doi: 10.1007/s40120-023-00575-5  Source

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Key clinical point: Eptinezumab vs placebo led to a greater reduction in migraine frequency and an improvement in migraine response in patients with migraine, irrespective of the type of prior treatment failure.

Major finding: Across weeks 1-12, patients receiving eptinezumab vs placebo experienced greater reductions in monthly migraine days (MMD) from baseline in all subgroups, with even greater improvements at weeks 13-24 (all P < .0001). Migraine responder rates (50% reduction in MMD) were also higher with eptinezumab vs placebo and increased following a second infusion (all P < .0001).

Study details: Findings are from a post hoc analysis of the DELIVER trial that included 890 patients with migraine who were randomly assigned to receive either 100 mg or 300 mg eptinezumab or placebo.

Disclosures: The study was sponsored and funded by H. Lundbeck A/S. Several authors declared receiving personal fees, research support, or research funding from various sources. Four authors declared being full-time employees of or holding stocks in Lundbeck or one of its subsidiary companies.

Source: Pozo-Rosich P, Ashina M, Tepper SJ et al. Eptinezumab demonstrated efficacy regardless of prior preventive migraine treatment failure type: Post hoc analyses of the DELIVER study. Neurol Ther. 2024 (Jan 18). doi: 10.1007/s40120-023-00575-5  Source

Key clinical point: Eptinezumab vs placebo led to a greater reduction in migraine frequency and an improvement in migraine response in patients with migraine, irrespective of the type of prior treatment failure.

Major finding: Across weeks 1-12, patients receiving eptinezumab vs placebo experienced greater reductions in monthly migraine days (MMD) from baseline in all subgroups, with even greater improvements at weeks 13-24 (all P < .0001). Migraine responder rates (50% reduction in MMD) were also higher with eptinezumab vs placebo and increased following a second infusion (all P < .0001).

Study details: Findings are from a post hoc analysis of the DELIVER trial that included 890 patients with migraine who were randomly assigned to receive either 100 mg or 300 mg eptinezumab or placebo.

Disclosures: The study was sponsored and funded by H. Lundbeck A/S. Several authors declared receiving personal fees, research support, or research funding from various sources. Four authors declared being full-time employees of or holding stocks in Lundbeck or one of its subsidiary companies.

Source: Pozo-Rosich P, Ashina M, Tepper SJ et al. Eptinezumab demonstrated efficacy regardless of prior preventive migraine treatment failure type: Post hoc analyses of the DELIVER study. Neurol Ther. 2024 (Jan 18). doi: 10.1007/s40120-023-00575-5  Source

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Migraine and Onset of Inflammatory Bowel Disease: Is There a Link?

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Key clinical point: Patients diagnosed with migraine should be monitored for the potential onset of inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC); particularly, men with migraine may require increased monitoring for the development of UC.

Major finding: Patients with migraine had a higher risk for IBD (adjusted hazard ratio [aHR] 1.31; P < .0001), CD (aHR 1.58; P = .0002), and UC (aHR 1.26; P = .0004) than those without migraine. Presence of migraine increased the risk for UC more prominently in men (aHR 1.43; 95% CI 1.20-1.71) than in women (aHR 1.12; 95% CI 0.94-1.34; Pinteraction = .042).

Study details: The data come from a nationwide population-based cohort study that included 10,131,193 individuals who had undergone a national health examination conducted by the Korean National Health Insurance Service in 2009, of which 281,144 patients had migraine.

Disclosures: This study did not disclose the funding source. The authors declared no competing interests.

Source: Lee CH, Han K, Lee HJ et al. Migraine is associated with the development of adult patients with inflammatory bowel disease: A nationwide, population-based study. Sci Rep. 2024;14:1157 (Jan 12).  doi: 10.1038/s41598-024-51455-3  Source.

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Key clinical point: Patients diagnosed with migraine should be monitored for the potential onset of inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC); particularly, men with migraine may require increased monitoring for the development of UC.

Major finding: Patients with migraine had a higher risk for IBD (adjusted hazard ratio [aHR] 1.31; P < .0001), CD (aHR 1.58; P = .0002), and UC (aHR 1.26; P = .0004) than those without migraine. Presence of migraine increased the risk for UC more prominently in men (aHR 1.43; 95% CI 1.20-1.71) than in women (aHR 1.12; 95% CI 0.94-1.34; Pinteraction = .042).

Study details: The data come from a nationwide population-based cohort study that included 10,131,193 individuals who had undergone a national health examination conducted by the Korean National Health Insurance Service in 2009, of which 281,144 patients had migraine.

Disclosures: This study did not disclose the funding source. The authors declared no competing interests.

Source: Lee CH, Han K, Lee HJ et al. Migraine is associated with the development of adult patients with inflammatory bowel disease: A nationwide, population-based study. Sci Rep. 2024;14:1157 (Jan 12).  doi: 10.1038/s41598-024-51455-3  Source.

Key clinical point: Patients diagnosed with migraine should be monitored for the potential onset of inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC); particularly, men with migraine may require increased monitoring for the development of UC.

Major finding: Patients with migraine had a higher risk for IBD (adjusted hazard ratio [aHR] 1.31; P < .0001), CD (aHR 1.58; P = .0002), and UC (aHR 1.26; P = .0004) than those without migraine. Presence of migraine increased the risk for UC more prominently in men (aHR 1.43; 95% CI 1.20-1.71) than in women (aHR 1.12; 95% CI 0.94-1.34; Pinteraction = .042).

Study details: The data come from a nationwide population-based cohort study that included 10,131,193 individuals who had undergone a national health examination conducted by the Korean National Health Insurance Service in 2009, of which 281,144 patients had migraine.

Disclosures: This study did not disclose the funding source. The authors declared no competing interests.

Source: Lee CH, Han K, Lee HJ et al. Migraine is associated with the development of adult patients with inflammatory bowel disease: A nationwide, population-based study. Sci Rep. 2024;14:1157 (Jan 12).  doi: 10.1038/s41598-024-51455-3  Source.

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