Clinical Edge Journal Scan

Key clinical point: In patients with active rheumatoid arthritis (RA), disproportionate articular pain (DP) was prevalent and sarilumab fared better than adalimumab or placebo in reducing DP and achieving clinical outcomes.

Major finding: At baseline, 23% of patients had DP. At week 24, a numerically lower proportion of patients experienced DP (15% vs 27%) and a higher proportion of patients achieved a Clinical Disease Activity Index of ≤10 (40% vs 17%) and American College of Rheumatology 50 response (42% vs 28%) with sarilumab vs adalimumab, with results being similar for sarilumab vs placebo.

Study details: This post hoc analysis of three phase 3 trials and their open label extension studies included 1531 patients with RA and intolerance or inadequate response to methotrexate/tumor necrosis factor inhibitors who received sarilumab, adalimumab, or placebo.

Disclosures: This study was funded by Sanofi and Regeneron Pharmaceuticals, Inc. Three authors declared being employees of or holding stock or stock options in Sanofi. Several authors reported ties with Sanofi, Regeneron Pharmaceuticals, and other sources.

Source: Choy E et al. Disproportionate articular pain is a frequent phenomenon in rheumatoid arthritis and responds to treatment with sarilumab. Rheumatology (Oxford). 2022 (Nov 22). Doi: 10.1093/rheumatology/keac659

Key clinical point: In patients with active rheumatoid arthritis (RA), disproportionate articular pain (DP) was prevalent and sarilumab fared better than adalimumab or placebo in reducing DP and achieving clinical outcomes.

Major finding: At baseline, 23% of patients had DP. At week 24, a numerically lower proportion of patients experienced DP (15% vs 27%) and a higher proportion of patients achieved a Clinical Disease Activity Index of ≤10 (40% vs 17%) and American College of Rheumatology 50 response (42% vs 28%) with sarilumab vs adalimumab, with results being similar for sarilumab vs placebo.

Study details: This post hoc analysis of three phase 3 trials and their open label extension studies included 1531 patients with RA and intolerance or inadequate response to methotrexate/tumor necrosis factor inhibitors who received sarilumab, adalimumab, or placebo.

Disclosures: This study was funded by Sanofi and Regeneron Pharmaceuticals, Inc. Three authors declared being employees of or holding stock or stock options in Sanofi. Several authors reported ties with Sanofi, Regeneron Pharmaceuticals, and other sources.

Source: Choy E et al. Disproportionate articular pain is a frequent phenomenon in rheumatoid arthritis and responds to treatment with sarilumab. Rheumatology (Oxford). 2022 (Nov 22). Doi: 10.1093/rheumatology/keac659

Key clinical point: In patients with active rheumatoid arthritis (RA), disproportionate articular pain (DP) was prevalent and sarilumab fared better than adalimumab or placebo in reducing DP and achieving clinical outcomes.

Major finding: At baseline, 23% of patients had DP. At week 24, a numerically lower proportion of patients experienced DP (15% vs 27%) and a higher proportion of patients achieved a Clinical Disease Activity Index of ≤10 (40% vs 17%) and American College of Rheumatology 50 response (42% vs 28%) with sarilumab vs adalimumab, with results being similar for sarilumab vs placebo.

Study details: This post hoc analysis of three phase 3 trials and their open label extension studies included 1531 patients with RA and intolerance or inadequate response to methotrexate/tumor necrosis factor inhibitors who received sarilumab, adalimumab, or placebo.

Disclosures: This study was funded by Sanofi and Regeneron Pharmaceuticals, Inc. Three authors declared being employees of or holding stock or stock options in Sanofi. Several authors reported ties with Sanofi, Regeneron Pharmaceuticals, and other sources.

Source: Choy E et al. Disproportionate articular pain is a frequent phenomenon in rheumatoid arthritis and responds to treatment with sarilumab. Rheumatology (Oxford). 2022 (Nov 22). Doi: 10.1093/rheumatology/keac659

Key clinical point: Patients with late-onset rheumatoid arthritis (LORA) and younger-onset rheumatoid arthritis (YORA) had similar prognosis, but patients with LORA who reached remission were more likely to be on a less intensive treatment regimen.

Major finding: Time to remission was similar among patients with LORA and YORA (P = .36). Patients with LORA vs YORA were less likely to be on biologics or Janus kinase inhibitors (16% vs 27%; P = .0039) and more likely to be on a single conventional synthetic disease-modifying antirheumatic drug (34% vs 27%; P = .0039) and oral glucocorticoids (27% vs 13%; P < .0001) at the time of remission.

Study details: This prospective cohort study included 872 patients diagnosed with RA at an age of ≥60 years (LORA; n = 354) or <60 years (YORA; n = 518).

Disclosures: This study was funded by peer-reviewed grants from the Canadian Arthritis Network and others and unrestricted grants from AbbVie, Novartis, and other sources. The authors declared no conflicts of interest.

Source: Li X et al. Late‑onset rheumatoid arthritis has a similar time to remission as younger‑onset rheumatoid arthritis: Results from the Ontario Best Practices Research Initiative. Arthritis Res Ther. 2022;24:255 (Nov 19). Doi: 10.1186/s13075-022-02952-1

Key clinical point: Patients with late-onset rheumatoid arthritis (LORA) and younger-onset rheumatoid arthritis (YORA) had similar prognosis, but patients with LORA who reached remission were more likely to be on a less intensive treatment regimen.

Major finding: Time to remission was similar among patients with LORA and YORA (P = .36). Patients with LORA vs YORA were less likely to be on biologics or Janus kinase inhibitors (16% vs 27%; P = .0039) and more likely to be on a single conventional synthetic disease-modifying antirheumatic drug (34% vs 27%; P = .0039) and oral glucocorticoids (27% vs 13%; P < .0001) at the time of remission.

Study details: This prospective cohort study included 872 patients diagnosed with RA at an age of ≥60 years (LORA; n = 354) or <60 years (YORA; n = 518).

Disclosures: This study was funded by peer-reviewed grants from the Canadian Arthritis Network and others and unrestricted grants from AbbVie, Novartis, and other sources. The authors declared no conflicts of interest.

Source: Li X et al. Late‑onset rheumatoid arthritis has a similar time to remission as younger‑onset rheumatoid arthritis: Results from the Ontario Best Practices Research Initiative. Arthritis Res Ther. 2022;24:255 (Nov 19). Doi: 10.1186/s13075-022-02952-1

Key clinical point: Patients with late-onset rheumatoid arthritis (LORA) and younger-onset rheumatoid arthritis (YORA) had similar prognosis, but patients with LORA who reached remission were more likely to be on a less intensive treatment regimen.

Major finding: Time to remission was similar among patients with LORA and YORA (P = .36). Patients with LORA vs YORA were less likely to be on biologics or Janus kinase inhibitors (16% vs 27%; P = .0039) and more likely to be on a single conventional synthetic disease-modifying antirheumatic drug (34% vs 27%; P = .0039) and oral glucocorticoids (27% vs 13%; P < .0001) at the time of remission.

Study details: This prospective cohort study included 872 patients diagnosed with RA at an age of ≥60 years (LORA; n = 354) or <60 years (YORA; n = 518).

Disclosures: This study was funded by peer-reviewed grants from the Canadian Arthritis Network and others and unrestricted grants from AbbVie, Novartis, and other sources. The authors declared no conflicts of interest.

Source: Li X et al. Late‑onset rheumatoid arthritis has a similar time to remission as younger‑onset rheumatoid arthritis: Results from the Ontario Best Practices Research Initiative. Arthritis Res Ther. 2022;24:255 (Nov 19). Doi: 10.1186/s13075-022-02952-1

Key clinical point: The addition of a tumor necrosis factor inhibitor (TNFi) or hydroxychloroquine+sulfasalazine (triple therapy) to weekly methotrexate significantly reduced atherosclerotic vascular inflammation in patients with rheumatoid arthritis (RA); however, TNFi was not associated with greater improvements than triple therapy.

Major finding: Over 24 weeks, the arterial target-to-background ratio (TBR) in carotid arteries or aorta reduced significantly with TNFi (Δ −0.24; P = .001) and triple therapy (Δ −0.19; P = .001), with no significant difference in TBR improvement between the two treatment groups (P = .79).

Study details: Findings are from the phase 4 TARGET trial including 115 patients with active RA despite being on weekly methotrexate who were randomly assigned to add TNFi (adalimumab or etanercept) or hydroxychloroquine+sulfasalazine.

Disclosures: This study was funded by the US National Institutes of Health National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIH-NIAMS). The study drug was supplied by AbbVie and Amgen. Four authors declared receiving research support, unrestricted grants, or royalties, being co-inventors on patents, or consulting for various sources unrelated to current study.

Source: Solomon DH et al for the TARGET Trial Consortium. Reducing cardiovascular risk with immunomodulators: A randomised active comparator trial among patients with rheumatoid arthritis. Ann Rheum Dis. 2022 (Nov 30). Doi: 10.1136/ard-2022-223302

Key clinical point: The addition of a tumor necrosis factor inhibitor (TNFi) or hydroxychloroquine+sulfasalazine (triple therapy) to weekly methotrexate significantly reduced atherosclerotic vascular inflammation in patients with rheumatoid arthritis (RA); however, TNFi was not associated with greater improvements than triple therapy.

Major finding: Over 24 weeks, the arterial target-to-background ratio (TBR) in carotid arteries or aorta reduced significantly with TNFi (Δ −0.24; P = .001) and triple therapy (Δ −0.19; P = .001), with no significant difference in TBR improvement between the two treatment groups (P = .79).

Study details: Findings are from the phase 4 TARGET trial including 115 patients with active RA despite being on weekly methotrexate who were randomly assigned to add TNFi (adalimumab or etanercept) or hydroxychloroquine+sulfasalazine.

Disclosures: This study was funded by the US National Institutes of Health National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIH-NIAMS). The study drug was supplied by AbbVie and Amgen. Four authors declared receiving research support, unrestricted grants, or royalties, being co-inventors on patents, or consulting for various sources unrelated to current study.

Source: Solomon DH et al for the TARGET Trial Consortium. Reducing cardiovascular risk with immunomodulators: A randomised active comparator trial among patients with rheumatoid arthritis. Ann Rheum Dis. 2022 (Nov 30). Doi: 10.1136/ard-2022-223302

Key clinical point: The addition of a tumor necrosis factor inhibitor (TNFi) or hydroxychloroquine+sulfasalazine (triple therapy) to weekly methotrexate significantly reduced atherosclerotic vascular inflammation in patients with rheumatoid arthritis (RA); however, TNFi was not associated with greater improvements than triple therapy.

Major finding: Over 24 weeks, the arterial target-to-background ratio (TBR) in carotid arteries or aorta reduced significantly with TNFi (Δ −0.24; P = .001) and triple therapy (Δ −0.19; P = .001), with no significant difference in TBR improvement between the two treatment groups (P = .79).

Study details: Findings are from the phase 4 TARGET trial including 115 patients with active RA despite being on weekly methotrexate who were randomly assigned to add TNFi (adalimumab or etanercept) or hydroxychloroquine+sulfasalazine.

Disclosures: This study was funded by the US National Institutes of Health National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIH-NIAMS). The study drug was supplied by AbbVie and Amgen. Four authors declared receiving research support, unrestricted grants, or royalties, being co-inventors on patents, or consulting for various sources unrelated to current study.

Source: Solomon DH et al for the TARGET Trial Consortium. Reducing cardiovascular risk with immunomodulators: A randomised active comparator trial among patients with rheumatoid arthritis. Ann Rheum Dis. 2022 (Nov 30). Doi: 10.1136/ard-2022-223302

Key clinical point: Baricitinib monotherapy was as effective as baricitinib plus methotrexate therapy with high drug retention rates in patients with rheumatoid arthritis (RA), suggesting baricitinib monotherapy as a viable option in the case of methotrexate intolerance.

Major finding: The 28-joint Disease Activity Scores based on Erythrocyte Sedimentation Rate were not significantly different at all time points over 96 weeks (log-rank P = .44) and drug survival rates at 1 year (69% vs 67%) and 2 years (62% vs 56%) were comparable in the baricitinib alone vs baricitinib+methotrexate arm. No new safety signals were identified.

Study details: This prospective observational study included 139 patients with RA who switched to baricitinib monotherapy or baricitinib plus methotrexate therapy because of high disease activity or intolerance to previous conventional synthetic and biologic disease-modifying antirheumatic drugs.

Disclosures: This study was supported by the Deutsche Forschungsgemeinschaft and other sources. Several authors reported receiving speaker honoraria or travel support or serving as consultants for various sources.

Source: Bayat S et al. Efficacy and drug persistence of baricitinib monotherapy is similar to combination therapy in patients with active RA: A prospective observational study. RMD Open. 2022;8:e002674 (Nov 21). Doi: 10.1136/rmdopen-2022-002674

Key clinical point: Baricitinib monotherapy was as effective as baricitinib plus methotrexate therapy with high drug retention rates in patients with rheumatoid arthritis (RA), suggesting baricitinib monotherapy as a viable option in the case of methotrexate intolerance.

Major finding: The 28-joint Disease Activity Scores based on Erythrocyte Sedimentation Rate were not significantly different at all time points over 96 weeks (log-rank P = .44) and drug survival rates at 1 year (69% vs 67%) and 2 years (62% vs 56%) were comparable in the baricitinib alone vs baricitinib+methotrexate arm. No new safety signals were identified.

Study details: This prospective observational study included 139 patients with RA who switched to baricitinib monotherapy or baricitinib plus methotrexate therapy because of high disease activity or intolerance to previous conventional synthetic and biologic disease-modifying antirheumatic drugs.

Disclosures: This study was supported by the Deutsche Forschungsgemeinschaft and other sources. Several authors reported receiving speaker honoraria or travel support or serving as consultants for various sources.

Source: Bayat S et al. Efficacy and drug persistence of baricitinib monotherapy is similar to combination therapy in patients with active RA: A prospective observational study. RMD Open. 2022;8:e002674 (Nov 21). Doi: 10.1136/rmdopen-2022-002674

Key clinical point: Baricitinib monotherapy was as effective as baricitinib plus methotrexate therapy with high drug retention rates in patients with rheumatoid arthritis (RA), suggesting baricitinib monotherapy as a viable option in the case of methotrexate intolerance.

Major finding: The 28-joint Disease Activity Scores based on Erythrocyte Sedimentation Rate were not significantly different at all time points over 96 weeks (log-rank P = .44) and drug survival rates at 1 year (69% vs 67%) and 2 years (62% vs 56%) were comparable in the baricitinib alone vs baricitinib+methotrexate arm. No new safety signals were identified.

Study details: This prospective observational study included 139 patients with RA who switched to baricitinib monotherapy or baricitinib plus methotrexate therapy because of high disease activity or intolerance to previous conventional synthetic and biologic disease-modifying antirheumatic drugs.

Disclosures: This study was supported by the Deutsche Forschungsgemeinschaft and other sources. Several authors reported receiving speaker honoraria or travel support or serving as consultants for various sources.

Source: Bayat S et al. Efficacy and drug persistence of baricitinib monotherapy is similar to combination therapy in patients with active RA: A prospective observational study. RMD Open. 2022;8:e002674 (Nov 21). Doi: 10.1136/rmdopen-2022-002674

Key clinical point: The use of conventional disease-modifying antirheumatic drugs did not increase the risk for rheumatoid arthritis-associated interstitial lung disease (RA-ILD) progression, except leflunomide, which increased the risk for ILD-progression in patients with severe ILD.

Major finding: Overall, the use vs no use of methotrexate, tacrolimus, or leflunomide was not associated with an increased risk for ILD progression; however, leflunomide significantly increased the risk for ILD progression in patients with reduced lung function (adjusted hazard ratio 8.42; 95% CI 2.61-27.15).

Study details: This prospective cohort study included 143 patients with RA-ILD who received methotrexate, leflunomide, or tacrolimus.

Disclosures: This study was supported by Seoul National University Hospital and Korea Health Technology R&D Project funded by the Ministry of Health and Welfare, Republic of Korea. The authors declared no conflicts of interest.

Source: Kim J-W et al. Methotrexate, leflunomide, and tacrolimus use and the progression of rheumatoid arthritis-associated interstitial lung disease. Rheumatology (Oxford). 2022 (Nov 17). Doi: 10.1093/rheumatology/keac651

Key clinical point: The use of conventional disease-modifying antirheumatic drugs did not increase the risk for rheumatoid arthritis-associated interstitial lung disease (RA-ILD) progression, except leflunomide, which increased the risk for ILD-progression in patients with severe ILD.

Major finding: Overall, the use vs no use of methotrexate, tacrolimus, or leflunomide was not associated with an increased risk for ILD progression; however, leflunomide significantly increased the risk for ILD progression in patients with reduced lung function (adjusted hazard ratio 8.42; 95% CI 2.61-27.15).

Study details: This prospective cohort study included 143 patients with RA-ILD who received methotrexate, leflunomide, or tacrolimus.

Disclosures: This study was supported by Seoul National University Hospital and Korea Health Technology R&D Project funded by the Ministry of Health and Welfare, Republic of Korea. The authors declared no conflicts of interest.

Source: Kim J-W et al. Methotrexate, leflunomide, and tacrolimus use and the progression of rheumatoid arthritis-associated interstitial lung disease. Rheumatology (Oxford). 2022 (Nov 17). Doi: 10.1093/rheumatology/keac651

Key clinical point: The use of conventional disease-modifying antirheumatic drugs did not increase the risk for rheumatoid arthritis-associated interstitial lung disease (RA-ILD) progression, except leflunomide, which increased the risk for ILD-progression in patients with severe ILD.

Major finding: Overall, the use vs no use of methotrexate, tacrolimus, or leflunomide was not associated with an increased risk for ILD progression; however, leflunomide significantly increased the risk for ILD progression in patients with reduced lung function (adjusted hazard ratio 8.42; 95% CI 2.61-27.15).

Study details: This prospective cohort study included 143 patients with RA-ILD who received methotrexate, leflunomide, or tacrolimus.

Disclosures: This study was supported by Seoul National University Hospital and Korea Health Technology R&D Project funded by the Ministry of Health and Welfare, Republic of Korea. The authors declared no conflicts of interest.

Source: Kim J-W et al. Methotrexate, leflunomide, and tacrolimus use and the progression of rheumatoid arthritis-associated interstitial lung disease. Rheumatology (Oxford). 2022 (Nov 17). Doi: 10.1093/rheumatology/keac651

When I hear about a new drug for inflammatory skin disease that has a novel target, the first thing I do is Google what happens when you have a deficiency in that pathway. For OX40, the first thing that comes up is "inherited human OX40 deficiency underlying classic Kaposi sarcoma of childhood."¹ That doesn't make this target seem appealing to me. While I might use a new drug targeting this pathway if other options fail, drugs targeting this pathway would not be my first choice, even if clinical trial safety data looked good. Clinical trials are powered to assess efficacy and common safety issues but tend not to be large enough to fully characterize rare risks.

Black box warnings on topical calcineurin inhibitors seem dumb to me. I think black box warnings on topical calcineurin inhibitors would be truly ridiculous, even laughable, except that laughing is not appropriate because these misguided warnings may be hurting our patients. These black box warnings on topical calcineurin inhibitors may exemplify the limitations of governmental bureaucracies. There doesn't seem to be a strong rationale for why these black box warnings were placed on topical calcineurin inhibitors initially. Why regulators haven't removed these black box warnings since then is baffling, as topical calcineurin inhibitors are considerably safer for patients than the alternative, topical corticosteroids. We have good evidence that topical calcineurin inhibitors do not cause cancer in our patients. The continued presence of black box warnings on these products may undermine the credibility of FDA-mandated black box warnings on other products.

Hedderson and colleagues state, in a study of cardiovascular events and atopic dermatitis, "VTE [venous thromboembolism] and DVT [deep vein thrombosis] IRs [incidence rates] were markedly higher in this study than have been observed in the general US adult population (VTE: 2.0 [current study] vs. 1.1; DVT: 1.6 [current study] vs. 0.66 per 1000 person-years." I think that's misleading. The difference of only 1 in 1000 doesn't seem like a markedly higher rate to me and it's also unlikely to be clinically meaningful. Even if there is some increased relative risk of some type of cardiovascular event, even if the rate is doubled, that doesn't mean we need to screen or intervene. We need to be mindful of the absolute risks and not be moved by relative risks. We need to see cost-effectiveness studies showing that an intervention is valuable before we conclude that we should be doing some screening or intervention to chase down and increase the relative risk for some potential adverse event.

Additional Reference

1. Byun M, Ma CS, Akçay A et al. Inherited human OX40 deficiency underlying classic Kaposi sarcoma of childhood. J Exp Med. 2013;210(9):1743–1759. Doi: 10.1084/jem.20130592

When I hear about a new drug for inflammatory skin disease that has a novel target, the first thing I do is Google what happens when you have a deficiency in that pathway. For OX40, the first thing that comes up is "inherited human OX40 deficiency underlying classic Kaposi sarcoma of childhood."¹ That doesn't make this target seem appealing to me. While I might use a new drug targeting this pathway if other options fail, drugs targeting this pathway would not be my first choice, even if clinical trial safety data looked good. Clinical trials are powered to assess efficacy and common safety issues but tend not to be large enough to fully characterize rare risks.

Black box warnings on topical calcineurin inhibitors seem dumb to me. I think black box warnings on topical calcineurin inhibitors would be truly ridiculous, even laughable, except that laughing is not appropriate because these misguided warnings may be hurting our patients. These black box warnings on topical calcineurin inhibitors may exemplify the limitations of governmental bureaucracies. There doesn't seem to be a strong rationale for why these black box warnings were placed on topical calcineurin inhibitors initially. Why regulators haven't removed these black box warnings since then is baffling, as topical calcineurin inhibitors are considerably safer for patients than the alternative, topical corticosteroids. We have good evidence that topical calcineurin inhibitors do not cause cancer in our patients. The continued presence of black box warnings on these products may undermine the credibility of FDA-mandated black box warnings on other products.

Hedderson and colleagues state, in a study of cardiovascular events and atopic dermatitis, "VTE [venous thromboembolism] and DVT [deep vein thrombosis] IRs [incidence rates] were markedly higher in this study than have been observed in the general US adult population (VTE: 2.0 [current study] vs. 1.1; DVT: 1.6 [current study] vs. 0.66 per 1000 person-years." I think that's misleading. The difference of only 1 in 1000 doesn't seem like a markedly higher rate to me and it's also unlikely to be clinically meaningful. Even if there is some increased relative risk of some type of cardiovascular event, even if the rate is doubled, that doesn't mean we need to screen or intervene. We need to be mindful of the absolute risks and not be moved by relative risks. We need to see cost-effectiveness studies showing that an intervention is valuable before we conclude that we should be doing some screening or intervention to chase down and increase the relative risk for some potential adverse event.

Additional Reference

1. Byun M, Ma CS, Akçay A et al. Inherited human OX40 deficiency underlying classic Kaposi sarcoma of childhood. J Exp Med. 2013;210(9):1743–1759. Doi: 10.1084/jem.20130592

When I hear about a new drug for inflammatory skin disease that has a novel target, the first thing I do is Google what happens when you have a deficiency in that pathway. For OX40, the first thing that comes up is "inherited human OX40 deficiency underlying classic Kaposi sarcoma of childhood."¹ That doesn't make this target seem appealing to me. While I might use a new drug targeting this pathway if other options fail, drugs targeting this pathway would not be my first choice, even if clinical trial safety data looked good. Clinical trials are powered to assess efficacy and common safety issues but tend not to be large enough to fully characterize rare risks.

Black box warnings on topical calcineurin inhibitors seem dumb to me. I think black box warnings on topical calcineurin inhibitors would be truly ridiculous, even laughable, except that laughing is not appropriate because these misguided warnings may be hurting our patients. These black box warnings on topical calcineurin inhibitors may exemplify the limitations of governmental bureaucracies. There doesn't seem to be a strong rationale for why these black box warnings were placed on topical calcineurin inhibitors initially. Why regulators haven't removed these black box warnings since then is baffling, as topical calcineurin inhibitors are considerably safer for patients than the alternative, topical corticosteroids. We have good evidence that topical calcineurin inhibitors do not cause cancer in our patients. The continued presence of black box warnings on these products may undermine the credibility of FDA-mandated black box warnings on other products.

Hedderson and colleagues state, in a study of cardiovascular events and atopic dermatitis, "VTE [venous thromboembolism] and DVT [deep vein thrombosis] IRs [incidence rates] were markedly higher in this study than have been observed in the general US adult population (VTE: 2.0 [current study] vs. 1.1; DVT: 1.6 [current study] vs. 0.66 per 1000 person-years." I think that's misleading. The difference of only 1 in 1000 doesn't seem like a markedly higher rate to me and it's also unlikely to be clinically meaningful. Even if there is some increased relative risk of some type of cardiovascular event, even if the rate is doubled, that doesn't mean we need to screen or intervene. We need to be mindful of the absolute risks and not be moved by relative risks. We need to see cost-effectiveness studies showing that an intervention is valuable before we conclude that we should be doing some screening or intervention to chase down and increase the relative risk for some potential adverse event.

Additional Reference

1. Byun M, Ma CS, Akçay A et al. Inherited human OX40 deficiency underlying classic Kaposi sarcoma of childhood. J Exp Med. 2013;210(9):1743–1759. Doi: 10.1084/jem.20130592

Two new papers published recently provide evidence of the efficacy and safety of bimekizumab in psoriatic arthritis (PsA). Bimekizumab is a novel bispecific monoclonal antibody targeting interleukin (IL)-17A and IL-17F and is already approved for the treatment of chronic plaque psoriasis. McInnes and colleagues reported the results of the phase 3 BE OPTIMAL study, which included 852 patients with active PsA who were naive to biologic disease-modifying antirheumatic drugs (bDMARD) and were randomly assigned to receive bimekizumab, placebo, or adalimumab. At week 16, a significantly higher proportion of patients receiving bimekizumab vs placebo achieved ≥ 50% improvement in American College of Rheumatology response (ACR50; 44% vs 10%; odds ratio [OR] 7.1; P < .0001). Compared with placebo, significant improvements were also noted in psoriasis, enthesitis, and dactylitis in the bimekizumab group and there was less progression of radiographic damage.

Bimekizumab was also demonstrated to be beneficial in PsA patients with inadequate response or intolerance to tumor necrosis factor inhibitors (TNFi). In the phase 3 BE COMPLETE study, which included 400 patients with active PsA and previous inadequate response or intolerance to TNFi, patients were randomly assigned to receive 160 mg subcutaneous bimekizumab every 4 weeks or placebo. Merola and colleagues reported that at week 16, a significantly higher proportion of patients receiving bimekizumab vs placebo achieved ACR50 response (43% vs 7%; OR 11.1; P < .0001). Thus, bimekizumab is a welcome addition to the treatment portfolio we have for PsA. In regard to side effects of special concern when inhibiting IL-17, bimekizumab was associated with higher risk for oral and genital candidiasis, occurring in 4% of the treated patients within 16 weeks in the two studies; however, no cases of systemic fungal infections occurred. The incidence of inflammatory bowel disease was also very low, but head-to-head studies against other available agents would be required to help rheumatologists decide the place of bimekizumab in PsA management.

A common clinical question is whether axial PsA is similar to ankylosing spondylitis (AS) with psoriasis. Assuming that it is, clinicians have used treatments approved for AS for managing axial PsA. Recent studies have questioned this assumption, however. Michelena and colleagues conducted a cross-sectional study that included 109 patients with axial PsA and 127 patients with AS and psoriasis from the REGISPONSER registry. Compared with patients with AS and psoriasis, patients with human leukocyte antigen (HLA)-B27–negative axial PsA had less inflammatory pain (P = .002), anterior uveitis (P = .014), and structural damage (P < .001), along with a higher prevalence of nail disease (P = .009). Patients with HLA-B27–positive axial PsA vs AS and psoriasis were similar but had less structural damage to the spine (P < .001). Thus, there seem to be significant clinical and genetic differences between these two diseases that require further investigation. Lack of an accepted definition of axial PsA, however, is a hindrance to multiple high-quality genetic, clinical, and interventional studies comparing axial PsA and AS with psoriasis.

Observational studies have recognized the clinical and familial association between psoriatic disease and Crohn's disease (CD), but such cross-sectional or retrospective studies cannot identify causal relationships. Mendelian randomization is a method used to identify causal relationships. Using this method, Sun and colleagues demonstrated that PsA was associated with a 31.9% increased risk for CD (P < .001) and genetically predicted CD was linked to a 44.8% higher risk for PsA (P = .001). No such association was found with ulcerative colitis. Thus, there is a bidirectional causal relationship between the two diseases. Patients with PsA should be evaluated for symptoms of CD, and those with CD for psoriatic disease, to facilitate early diagnosis and better long-term outcomes.

Two new papers published recently provide evidence of the efficacy and safety of bimekizumab in psoriatic arthritis (PsA). Bimekizumab is a novel bispecific monoclonal antibody targeting interleukin (IL)-17A and IL-17F and is already approved for the treatment of chronic plaque psoriasis. McInnes and colleagues reported the results of the phase 3 BE OPTIMAL study, which included 852 patients with active PsA who were naive to biologic disease-modifying antirheumatic drugs (bDMARD) and were randomly assigned to receive bimekizumab, placebo, or adalimumab. At week 16, a significantly higher proportion of patients receiving bimekizumab vs placebo achieved ≥ 50% improvement in American College of Rheumatology response (ACR50; 44% vs 10%; odds ratio [OR] 7.1; P < .0001). Compared with placebo, significant improvements were also noted in psoriasis, enthesitis, and dactylitis in the bimekizumab group and there was less progression of radiographic damage.

Bimekizumab was also demonstrated to be beneficial in PsA patients with inadequate response or intolerance to tumor necrosis factor inhibitors (TNFi). In the phase 3 BE COMPLETE study, which included 400 patients with active PsA and previous inadequate response or intolerance to TNFi, patients were randomly assigned to receive 160 mg subcutaneous bimekizumab every 4 weeks or placebo. Merola and colleagues reported that at week 16, a significantly higher proportion of patients receiving bimekizumab vs placebo achieved ACR50 response (43% vs 7%; OR 11.1; P < .0001). Thus, bimekizumab is a welcome addition to the treatment portfolio we have for PsA. In regard to side effects of special concern when inhibiting IL-17, bimekizumab was associated with higher risk for oral and genital candidiasis, occurring in 4% of the treated patients within 16 weeks in the two studies; however, no cases of systemic fungal infections occurred. The incidence of inflammatory bowel disease was also very low, but head-to-head studies against other available agents would be required to help rheumatologists decide the place of bimekizumab in PsA management.

A common clinical question is whether axial PsA is similar to ankylosing spondylitis (AS) with psoriasis. Assuming that it is, clinicians have used treatments approved for AS for managing axial PsA. Recent studies have questioned this assumption, however. Michelena and colleagues conducted a cross-sectional study that included 109 patients with axial PsA and 127 patients with AS and psoriasis from the REGISPONSER registry. Compared with patients with AS and psoriasis, patients with human leukocyte antigen (HLA)-B27–negative axial PsA had less inflammatory pain (P = .002), anterior uveitis (P = .014), and structural damage (P < .001), along with a higher prevalence of nail disease (P = .009). Patients with HLA-B27–positive axial PsA vs AS and psoriasis were similar but had less structural damage to the spine (P < .001). Thus, there seem to be significant clinical and genetic differences between these two diseases that require further investigation. Lack of an accepted definition of axial PsA, however, is a hindrance to multiple high-quality genetic, clinical, and interventional studies comparing axial PsA and AS with psoriasis.

Observational studies have recognized the clinical and familial association between psoriatic disease and Crohn's disease (CD), but such cross-sectional or retrospective studies cannot identify causal relationships. Mendelian randomization is a method used to identify causal relationships. Using this method, Sun and colleagues demonstrated that PsA was associated with a 31.9% increased risk for CD (P < .001) and genetically predicted CD was linked to a 44.8% higher risk for PsA (P = .001). No such association was found with ulcerative colitis. Thus, there is a bidirectional causal relationship between the two diseases. Patients with PsA should be evaluated for symptoms of CD, and those with CD for psoriatic disease, to facilitate early diagnosis and better long-term outcomes.

Two new papers published recently provide evidence of the efficacy and safety of bimekizumab in psoriatic arthritis (PsA). Bimekizumab is a novel bispecific monoclonal antibody targeting interleukin (IL)-17A and IL-17F and is already approved for the treatment of chronic plaque psoriasis. McInnes and colleagues reported the results of the phase 3 BE OPTIMAL study, which included 852 patients with active PsA who were naive to biologic disease-modifying antirheumatic drugs (bDMARD) and were randomly assigned to receive bimekizumab, placebo, or adalimumab. At week 16, a significantly higher proportion of patients receiving bimekizumab vs placebo achieved ≥ 50% improvement in American College of Rheumatology response (ACR50; 44% vs 10%; odds ratio [OR] 7.1; P < .0001). Compared with placebo, significant improvements were also noted in psoriasis, enthesitis, and dactylitis in the bimekizumab group and there was less progression of radiographic damage.

Bimekizumab was also demonstrated to be beneficial in PsA patients with inadequate response or intolerance to tumor necrosis factor inhibitors (TNFi). In the phase 3 BE COMPLETE study, which included 400 patients with active PsA and previous inadequate response or intolerance to TNFi, patients were randomly assigned to receive 160 mg subcutaneous bimekizumab every 4 weeks or placebo. Merola and colleagues reported that at week 16, a significantly higher proportion of patients receiving bimekizumab vs placebo achieved ACR50 response (43% vs 7%; OR 11.1; P < .0001). Thus, bimekizumab is a welcome addition to the treatment portfolio we have for PsA. In regard to side effects of special concern when inhibiting IL-17, bimekizumab was associated with higher risk for oral and genital candidiasis, occurring in 4% of the treated patients within 16 weeks in the two studies; however, no cases of systemic fungal infections occurred. The incidence of inflammatory bowel disease was also very low, but head-to-head studies against other available agents would be required to help rheumatologists decide the place of bimekizumab in PsA management.

A common clinical question is whether axial PsA is similar to ankylosing spondylitis (AS) with psoriasis. Assuming that it is, clinicians have used treatments approved for AS for managing axial PsA. Recent studies have questioned this assumption, however. Michelena and colleagues conducted a cross-sectional study that included 109 patients with axial PsA and 127 patients with AS and psoriasis from the REGISPONSER registry. Compared with patients with AS and psoriasis, patients with human leukocyte antigen (HLA)-B27–negative axial PsA had less inflammatory pain (P = .002), anterior uveitis (P = .014), and structural damage (P < .001), along with a higher prevalence of nail disease (P = .009). Patients with HLA-B27–positive axial PsA vs AS and psoriasis were similar but had less structural damage to the spine (P < .001). Thus, there seem to be significant clinical and genetic differences between these two diseases that require further investigation. Lack of an accepted definition of axial PsA, however, is a hindrance to multiple high-quality genetic, clinical, and interventional studies comparing axial PsA and AS with psoriasis.

Observational studies have recognized the clinical and familial association between psoriatic disease and Crohn's disease (CD), but such cross-sectional or retrospective studies cannot identify causal relationships. Mendelian randomization is a method used to identify causal relationships. Using this method, Sun and colleagues demonstrated that PsA was associated with a 31.9% increased risk for CD (P < .001) and genetically predicted CD was linked to a 44.8% higher risk for PsA (P = .001). No such association was found with ulcerative colitis. Thus, there is a bidirectional causal relationship between the two diseases. Patients with PsA should be evaluated for symptoms of CD, and those with CD for psoriatic disease, to facilitate early diagnosis and better long-term outcomes.

January's theme is migraine triggers. We'll take a look at three recent studies that have tried to better determine the nature of specific triggers for headache.

One of the most common and reportedly consistent migraine triggers is exposure to alcohol, and the International Classification of Headache Disorders (ICHD-3) includes alcohol-induced headache as a secondary headache. Little is known regarding the association between migraine and alcohol. Vives-Mestres and colleagues investigated the alcohol intake of people using a digital health diary for headache. They specifically looked at the 48 hours preceding a migraine attack and whether alcohol was consumed, and also the number of beverages consumed. This was further adjusted for sex, age, and average weekly alcohol intake.

The N1-Headache Tracker is a digital headache diary that patients use to track their daily headache symptoms and inform them of potential migraine risk factors. Over a 90-day period, this study followed patients that did not meet the criteria for a diagnosis of chronic migraine. They also reported on their intake to the platform that they regularly consume alcohol. Of note, persons who never tracked alcohol consumption were excluded from this study. On intake to the platform, alcohol exposure was characterized both as whether daily consumption of alcohol was occurring and as the total daily number of alcoholic beverages.

The primary outcome of this study was migraine attack 1 day after alcohol consumption. Participants were specifically asked if their headaches were diagnosed as migraine by a physician. Migraine attack onset was considered binary, and a logistic model was used to estimate the probability of having a migraine attack on any given day with the association of alcohol intake for up to 48 hours prior to that day.

A total of 487 people with migraine were included in this trial and they collectively contributed over 43,000 diary days; almost 6000 were first days of a migraine attack. Overall alcohol consumption was not considered high and was noted to vary between groups; people with lower frequency migraine tended to have higher rates of alcohol intake. No significant correlation was observed between the presence of migraine attacks within 48 hours after alcohol consumption. This did not vary among different probability models; a population-level model showed that the probability of a migraine attack 2 days after alcohol intake was 25% lower than the probability of an attack with no alcohol consumption. This was also true after adjustment for age, sex, and average number of alcoholic beverages per week.

The association between migraine and alcohol is complicated, and the concept of migraine triggers in general is very complex. Although over 70% of people with migraine say that they have a consistent trigger, and alcohol is consistently at the top of the list of those reported triggers, there does not appear to be a direct correlation between migraine and alcohol exposure. The greatest caveat of this study is the fact that people with chronic migraine were excluded. Further research should specifically investigate triggers such as alcohol in this population.

The use of proton pump inhibitors (PPI) has been shown in previous studies over the past few years to be associated with a number of neurologic events and risks, including impaired hearing, vision, and memory, as well as migraine occurrence. The specifics of this association are not well known — specifically, whether the duration of use is the main factor, or whether it is acute exposure to a PPI medication that is a trigger. Kang and colleagues reviewed data in the Korean national database and developed a case-control model to study this association specifically.

The migraine and control groups were equally matched: They had the same demographics, smoking status, alcohol consumption, blood pressure range, fasting glucose, and total cholesterol. Past and current PPI use and comparisons of migraine occurrence were further differentiated among patients who were exposed to PPI medications for < 30 days, 30-365 days, and > 365 days.

The use of PPI treatments was noted to be linked to increased migraine regardless of duration, and regardless of the acute presence of the PPI. Even a history of prior PPI use was noted to increase the odds ratio of migraine development. This was significant among all subgroups, independent of age, sex, and other comorbidities. There was no difference in the presence of aura associated with migraine.

As we noted above, the concept of migraine triggers is overall poorly understood. This is even more the case when it comes to historical exposures. Although the use of PPI medications appears to be associated with the occurrence of migraine in this population, these medications are necessary in many instances, including in patients with severe gastritis and gastroesophageal reflux refractory to diet changes. It remains to be seen precisely how PPI medications would potentially lead to a higher incidence of migraine.

Among many of the triggers discussed, specific foods are commonly thought to be associated with migraine. Although there is scant evidence for a specific diet to improve migraine frequency, many patients are very interested in potential dietary changes that may help them. Prior studies and reviews have looked at gluten-free, dairy-free, low-carbohydrate, low-tyramine, and elimination diets — all of which were not associated with a significant improvement in migraine frequency or severity. Bakıran and colleagues sought to investigate an antioxidant-rich diet that included polyphenols and carotenoids — substances that may improve systemic inflammation, glucose metabolism, and oxidative stress.

Phytochemical-rich foods include fruits and vegetables (excluding potatoes) as well as nuts, whole grains, pulses, and olive oil. The phytochemical index is a tool used by dietitians and nutritionists to assess the phytochemical content in a diet.

A total of 90 patients who had a diagnosis of episodic migraine by a neurologist were enrolled. Individuals were excluded if they had a body mass index > 40 or < 18 or had other significant chronic comorbidities, such as hypertension, diabetes, hepatic or renal disease, or other neurologic conditions. Participants filled out a headache diary over 3 months; the Migraine Disability Assessment (MIDAS) questionnaire was also followed in order to assess migraine-related disability. Diet quality was cataloged as per patient records; patients also filled out a 3-day nonconsecutive food diary. This information was added to a food software program that calculated specific nutrients, including the phytochemical index.

Participants were divided into groups with good diet quality and poor diet quality based on their phytochemical index. No differences were seen in migraine frequency or disability between these groups, although mean attack duration was lower in those with poor diet quality. Severity was noted to be higher in those with poor diet quality; 75% of participants with poor diet quality experienced severe attacks.

Overall, the results of this study are very mixed. Participants on the recommended high phytochemical diet were seen to have lower severity of migraine but a prolonged duration of attack. There also was no correlation between this diet and either frequency or disability. This was a small study, and further research should focus on this among other diet changes that have the possibility to improve the quality of life of people with migraine.

January's theme is migraine triggers. We'll take a look at three recent studies that have tried to better determine the nature of specific triggers for headache.

One of the most common and reportedly consistent migraine triggers is exposure to alcohol, and the International Classification of Headache Disorders (ICHD-3) includes alcohol-induced headache as a secondary headache. Little is known regarding the association between migraine and alcohol. Vives-Mestres and colleagues investigated the alcohol intake of people using a digital health diary for headache. They specifically looked at the 48 hours preceding a migraine attack and whether alcohol was consumed, and also the number of beverages consumed. This was further adjusted for sex, age, and average weekly alcohol intake.

The N1-Headache Tracker is a digital headache diary that patients use to track their daily headache symptoms and inform them of potential migraine risk factors. Over a 90-day period, this study followed patients that did not meet the criteria for a diagnosis of chronic migraine. They also reported on their intake to the platform that they regularly consume alcohol. Of note, persons who never tracked alcohol consumption were excluded from this study. On intake to the platform, alcohol exposure was characterized both as whether daily consumption of alcohol was occurring and as the total daily number of alcoholic beverages.

The primary outcome of this study was migraine attack 1 day after alcohol consumption. Participants were specifically asked if their headaches were diagnosed as migraine by a physician. Migraine attack onset was considered binary, and a logistic model was used to estimate the probability of having a migraine attack on any given day with the association of alcohol intake for up to 48 hours prior to that day.

A total of 487 people with migraine were included in this trial and they collectively contributed over 43,000 diary days; almost 6000 were first days of a migraine attack. Overall alcohol consumption was not considered high and was noted to vary between groups; people with lower frequency migraine tended to have higher rates of alcohol intake. No significant correlation was observed between the presence of migraine attacks within 48 hours after alcohol consumption. This did not vary among different probability models; a population-level model showed that the probability of a migraine attack 2 days after alcohol intake was 25% lower than the probability of an attack with no alcohol consumption. This was also true after adjustment for age, sex, and average number of alcoholic beverages per week.

The association between migraine and alcohol is complicated, and the concept of migraine triggers in general is very complex. Although over 70% of people with migraine say that they have a consistent trigger, and alcohol is consistently at the top of the list of those reported triggers, there does not appear to be a direct correlation between migraine and alcohol exposure. The greatest caveat of this study is the fact that people with chronic migraine were excluded. Further research should specifically investigate triggers such as alcohol in this population.

The use of proton pump inhibitors (PPI) has been shown in previous studies over the past few years to be associated with a number of neurologic events and risks, including impaired hearing, vision, and memory, as well as migraine occurrence. The specifics of this association are not well known — specifically, whether the duration of use is the main factor, or whether it is acute exposure to a PPI medication that is a trigger. Kang and colleagues reviewed data in the Korean national database and developed a case-control model to study this association specifically.

The migraine and control groups were equally matched: They had the same demographics, smoking status, alcohol consumption, blood pressure range, fasting glucose, and total cholesterol. Past and current PPI use and comparisons of migraine occurrence were further differentiated among patients who were exposed to PPI medications for < 30 days, 30-365 days, and > 365 days.

The use of PPI treatments was noted to be linked to increased migraine regardless of duration, and regardless of the acute presence of the PPI. Even a history of prior PPI use was noted to increase the odds ratio of migraine development. This was significant among all subgroups, independent of age, sex, and other comorbidities. There was no difference in the presence of aura associated with migraine.

As we noted above, the concept of migraine triggers is overall poorly understood. This is even more the case when it comes to historical exposures. Although the use of PPI medications appears to be associated with the occurrence of migraine in this population, these medications are necessary in many instances, including in patients with severe gastritis and gastroesophageal reflux refractory to diet changes. It remains to be seen precisely how PPI medications would potentially lead to a higher incidence of migraine.

Among many of the triggers discussed, specific foods are commonly thought to be associated with migraine. Although there is scant evidence for a specific diet to improve migraine frequency, many patients are very interested in potential dietary changes that may help them. Prior studies and reviews have looked at gluten-free, dairy-free, low-carbohydrate, low-tyramine, and elimination diets — all of which were not associated with a significant improvement in migraine frequency or severity. Bakıran and colleagues sought to investigate an antioxidant-rich diet that included polyphenols and carotenoids — substances that may improve systemic inflammation, glucose metabolism, and oxidative stress.

Phytochemical-rich foods include fruits and vegetables (excluding potatoes) as well as nuts, whole grains, pulses, and olive oil. The phytochemical index is a tool used by dietitians and nutritionists to assess the phytochemical content in a diet.

A total of 90 patients who had a diagnosis of episodic migraine by a neurologist were enrolled. Individuals were excluded if they had a body mass index > 40 or < 18 or had other significant chronic comorbidities, such as hypertension, diabetes, hepatic or renal disease, or other neurologic conditions. Participants filled out a headache diary over 3 months; the Migraine Disability Assessment (MIDAS) questionnaire was also followed in order to assess migraine-related disability. Diet quality was cataloged as per patient records; patients also filled out a 3-day nonconsecutive food diary. This information was added to a food software program that calculated specific nutrients, including the phytochemical index.

Participants were divided into groups with good diet quality and poor diet quality based on their phytochemical index. No differences were seen in migraine frequency or disability between these groups, although mean attack duration was lower in those with poor diet quality. Severity was noted to be higher in those with poor diet quality; 75% of participants with poor diet quality experienced severe attacks.

Overall, the results of this study are very mixed. Participants on the recommended high phytochemical diet were seen to have lower severity of migraine but a prolonged duration of attack. There also was no correlation between this diet and either frequency or disability. This was a small study, and further research should focus on this among other diet changes that have the possibility to improve the quality of life of people with migraine.

January's theme is migraine triggers. We'll take a look at three recent studies that have tried to better determine the nature of specific triggers for headache.

One of the most common and reportedly consistent migraine triggers is exposure to alcohol, and the International Classification of Headache Disorders (ICHD-3) includes alcohol-induced headache as a secondary headache. Little is known regarding the association between migraine and alcohol. Vives-Mestres and colleagues investigated the alcohol intake of people using a digital health diary for headache. They specifically looked at the 48 hours preceding a migraine attack and whether alcohol was consumed, and also the number of beverages consumed. This was further adjusted for sex, age, and average weekly alcohol intake.

The N1-Headache Tracker is a digital headache diary that patients use to track their daily headache symptoms and inform them of potential migraine risk factors. Over a 90-day period, this study followed patients that did not meet the criteria for a diagnosis of chronic migraine. They also reported on their intake to the platform that they regularly consume alcohol. Of note, persons who never tracked alcohol consumption were excluded from this study. On intake to the platform, alcohol exposure was characterized both as whether daily consumption of alcohol was occurring and as the total daily number of alcoholic beverages.

The primary outcome of this study was migraine attack 1 day after alcohol consumption. Participants were specifically asked if their headaches were diagnosed as migraine by a physician. Migraine attack onset was considered binary, and a logistic model was used to estimate the probability of having a migraine attack on any given day with the association of alcohol intake for up to 48 hours prior to that day.

A total of 487 people with migraine were included in this trial and they collectively contributed over 43,000 diary days; almost 6000 were first days of a migraine attack. Overall alcohol consumption was not considered high and was noted to vary between groups; people with lower frequency migraine tended to have higher rates of alcohol intake. No significant correlation was observed between the presence of migraine attacks within 48 hours after alcohol consumption. This did not vary among different probability models; a population-level model showed that the probability of a migraine attack 2 days after alcohol intake was 25% lower than the probability of an attack with no alcohol consumption. This was also true after adjustment for age, sex, and average number of alcoholic beverages per week.

The association between migraine and alcohol is complicated, and the concept of migraine triggers in general is very complex. Although over 70% of people with migraine say that they have a consistent trigger, and alcohol is consistently at the top of the list of those reported triggers, there does not appear to be a direct correlation between migraine and alcohol exposure. The greatest caveat of this study is the fact that people with chronic migraine were excluded. Further research should specifically investigate triggers such as alcohol in this population.

The use of proton pump inhibitors (PPI) has been shown in previous studies over the past few years to be associated with a number of neurologic events and risks, including impaired hearing, vision, and memory, as well as migraine occurrence. The specifics of this association are not well known — specifically, whether the duration of use is the main factor, or whether it is acute exposure to a PPI medication that is a trigger. Kang and colleagues reviewed data in the Korean national database and developed a case-control model to study this association specifically.

The migraine and control groups were equally matched: They had the same demographics, smoking status, alcohol consumption, blood pressure range, fasting glucose, and total cholesterol. Past and current PPI use and comparisons of migraine occurrence were further differentiated among patients who were exposed to PPI medications for < 30 days, 30-365 days, and > 365 days.

The use of PPI treatments was noted to be linked to increased migraine regardless of duration, and regardless of the acute presence of the PPI. Even a history of prior PPI use was noted to increase the odds ratio of migraine development. This was significant among all subgroups, independent of age, sex, and other comorbidities. There was no difference in the presence of aura associated with migraine.

As we noted above, the concept of migraine triggers is overall poorly understood. This is even more the case when it comes to historical exposures. Although the use of PPI medications appears to be associated with the occurrence of migraine in this population, these medications are necessary in many instances, including in patients with severe gastritis and gastroesophageal reflux refractory to diet changes. It remains to be seen precisely how PPI medications would potentially lead to a higher incidence of migraine.

Among many of the triggers discussed, specific foods are commonly thought to be associated with migraine. Although there is scant evidence for a specific diet to improve migraine frequency, many patients are very interested in potential dietary changes that may help them. Prior studies and reviews have looked at gluten-free, dairy-free, low-carbohydrate, low-tyramine, and elimination diets — all of which were not associated with a significant improvement in migraine frequency or severity. Bakıran and colleagues sought to investigate an antioxidant-rich diet that included polyphenols and carotenoids — substances that may improve systemic inflammation, glucose metabolism, and oxidative stress.

Phytochemical-rich foods include fruits and vegetables (excluding potatoes) as well as nuts, whole grains, pulses, and olive oil. The phytochemical index is a tool used by dietitians and nutritionists to assess the phytochemical content in a diet.

A total of 90 patients who had a diagnosis of episodic migraine by a neurologist were enrolled. Individuals were excluded if they had a body mass index > 40 or < 18 or had other significant chronic comorbidities, such as hypertension, diabetes, hepatic or renal disease, or other neurologic conditions. Participants filled out a headache diary over 3 months; the Migraine Disability Assessment (MIDAS) questionnaire was also followed in order to assess migraine-related disability. Diet quality was cataloged as per patient records; patients also filled out a 3-day nonconsecutive food diary. This information was added to a food software program that calculated specific nutrients, including the phytochemical index.

Participants were divided into groups with good diet quality and poor diet quality based on their phytochemical index. No differences were seen in migraine frequency or disability between these groups, although mean attack duration was lower in those with poor diet quality. Severity was noted to be higher in those with poor diet quality; 75% of participants with poor diet quality experienced severe attacks.

Overall, the results of this study are very mixed. Participants on the recommended high phytochemical diet were seen to have lower severity of migraine but a prolonged duration of attack. There also was no correlation between this diet and either frequency or disability. This was a small study, and further research should focus on this among other diet changes that have the possibility to improve the quality of life of people with migraine.

The risk for disease recurrence, and specifically distant relapse, for women with high-risk early breast cancer highlights the need for novel therapies in this population.^2,3 The phase 3 randomized monarchE trial investigated the role of the CDK4/6 inhibitor abemaciclib combined with endocrine therapy vs standard endocrine therapy alone in 5637 patients with high-risk (≥ 4 positive axillary nodes or 1-3 positive nodes and either grade 3 tumor, tumor size ≥ 5 cm or Ki-67 ≥ 20%) hormone receptor–positive/HER2-negative early breast cancer. At a median follow-up of 42 months, the median invasive disease-free survival (iDFS) benefit was sustained with abemaciclib + endocrine therapy vs endocrine therapy alone (HR 0.664; nominal P < .0001); the absolute 4-year iDFS benefit was 6.4% (85.8% in the abemaciclib + endocrine therapy group vs 79.4% in the endocrine therapy–alone group). Furthermore, this effect appeared to deepen over time, as the previous absolute iDFS differences were 2.8% (2 years) and 4.8% (3 years). Abemaciclib was associated with a higher rate of grade 3 or higher adverse events (49.9% vs 16.9%), the most common being neutropenia, leukopenia, and diarrhea (Johnston et al). Although adjuvant palbociclib trials (PALLAS⁴ and PENELOPE-B⁵) did not meet their primary endpoint, longer follow-up of monarchE and results from NATALEE with ribociclib are anxiously awaited to further define the role of CDK4/6 inhibitors in this space.

Aromatase inhibitors (AI) are an integral component of treatment for hormone receptor–positive breast cancer for many women. However, joint pain and stiffness associated with these agents can affect compliance. Various management strategies, including trials of alternative AI or endocrine therapies and pharmacologic (duloxetine) and non-pharmacologic (acupuncture,⁶ exercise) modalities, have been investigated. A randomized trial including 226 women with early-stage breast cancer receiving AI therapy with baseline joint pain (Brief Pain Inventory Worst Pain [BPI-WP] item score of ≥ 3) evaluated whether true acupuncture (TA) provided a sustained reduction in pain symptoms compared with sham acupuncture (SA) or waiting-list control (WC). Acupuncture protocols consisted of 6 weeks of intervention (2 sessions per week) followed by 1 session per week for another 6 weeks. At 52 weeks, mean BPI-WP scores were 1.08 points lower in the TA group compared with the SA group (P = .01) and were 0.99 points lower in the TA group compared with the WC group (P = .03) (Hershman et al). These data support consideration of acupuncture as a mechanism to help maintain patients on aromatase inhibitors, particularly for patients who wish to avoid or have not received benefit from pharmacologic therapy.

Additional References

1. Puglisi F, Gerratana L, Lambertini M, et al. Composite risk and benefit from adjuvant dose-dense chemotherapy in hormone receptor-positive breast cancer. NPJ Breast Cancer. 2021;7:82. Doi: 10.1038/s41523-021-00286-w
2. Salvo EM, Ramirez AO, Cueto J, et al. Risk of recurrence among patients with HR-positive, HER2-negative, early breast cancer receiving adjuvant endocrine therapy: A systematic review and meta-analysis. Breast. 2021;57:5-17. Doi: 10.1016/j.breast.2021.02.009
3. Sheffield KM, Peachey JR, Method M, et al. A real-world US study of recurrence risks using combined clinicopathological features in HR-positive, HER2-negative early breast cancer. Future Oncol.2022;18:2667-2682. Doi: 10.2217/fon-2022-0310
4. Mayer EL, Dueck AC, Martin M, et al. Palbociclib with adjuvant endocrine therapy in early breast cancer (PALLAS): Interim analysis of a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2021;22(2):212-222. Doi: Loibl S, Marmé F, Martin M, et al. Palbociclib for residual high-risk invasive HR-positive and HER2-negative early breast cancer-The Penelope-B trial. J Clin Oncol. 2021;39(14):1518-1530. Doi: Liu X, Lu J, Wang G, et al. Acupuncture for arthralgia induced by aromatase inhibitors in patients with breast cancer: A systematic review and meta-analysis. Integr Cancer Ther. 2021;20:1534735420980811. Doi: 10.1177/1534735420980811

The risk for disease recurrence, and specifically distant relapse, for women with high-risk early breast cancer highlights the need for novel therapies in this population.^2,3 The phase 3 randomized monarchE trial investigated the role of the CDK4/6 inhibitor abemaciclib combined with endocrine therapy vs standard endocrine therapy alone in 5637 patients with high-risk (≥ 4 positive axillary nodes or 1-3 positive nodes and either grade 3 tumor, tumor size ≥ 5 cm or Ki-67 ≥ 20%) hormone receptor–positive/HER2-negative early breast cancer. At a median follow-up of 42 months, the median invasive disease-free survival (iDFS) benefit was sustained with abemaciclib + endocrine therapy vs endocrine therapy alone (HR 0.664; nominal P < .0001); the absolute 4-year iDFS benefit was 6.4% (85.8% in the abemaciclib + endocrine therapy group vs 79.4% in the endocrine therapy–alone group). Furthermore, this effect appeared to deepen over time, as the previous absolute iDFS differences were 2.8% (2 years) and 4.8% (3 years). Abemaciclib was associated with a higher rate of grade 3 or higher adverse events (49.9% vs 16.9%), the most common being neutropenia, leukopenia, and diarrhea (Johnston et al). Although adjuvant palbociclib trials (PALLAS⁴ and PENELOPE-B⁵) did not meet their primary endpoint, longer follow-up of monarchE and results from NATALEE with ribociclib are anxiously awaited to further define the role of CDK4/6 inhibitors in this space.

Aromatase inhibitors (AI) are an integral component of treatment for hormone receptor–positive breast cancer for many women. However, joint pain and stiffness associated with these agents can affect compliance. Various management strategies, including trials of alternative AI or endocrine therapies and pharmacologic (duloxetine) and non-pharmacologic (acupuncture,⁶ exercise) modalities, have been investigated. A randomized trial including 226 women with early-stage breast cancer receiving AI therapy with baseline joint pain (Brief Pain Inventory Worst Pain [BPI-WP] item score of ≥ 3) evaluated whether true acupuncture (TA) provided a sustained reduction in pain symptoms compared with sham acupuncture (SA) or waiting-list control (WC). Acupuncture protocols consisted of 6 weeks of intervention (2 sessions per week) followed by 1 session per week for another 6 weeks. At 52 weeks, mean BPI-WP scores were 1.08 points lower in the TA group compared with the SA group (P = .01) and were 0.99 points lower in the TA group compared with the WC group (P = .03) (Hershman et al). These data support consideration of acupuncture as a mechanism to help maintain patients on aromatase inhibitors, particularly for patients who wish to avoid or have not received benefit from pharmacologic therapy.

Additional References

1. Puglisi F, Gerratana L, Lambertini M, et al. Composite risk and benefit from adjuvant dose-dense chemotherapy in hormone receptor-positive breast cancer. NPJ Breast Cancer. 2021;7:82. Doi: 10.1038/s41523-021-00286-w
2. Salvo EM, Ramirez AO, Cueto J, et al. Risk of recurrence among patients with HR-positive, HER2-negative, early breast cancer receiving adjuvant endocrine therapy: A systematic review and meta-analysis. Breast. 2021;57:5-17. Doi: 10.1016/j.breast.2021.02.009
3. Sheffield KM, Peachey JR, Method M, et al. A real-world US study of recurrence risks using combined clinicopathological features in HR-positive, HER2-negative early breast cancer. Future Oncol.2022;18:2667-2682. Doi: 10.2217/fon-2022-0310
4. Mayer EL, Dueck AC, Martin M, et al. Palbociclib with adjuvant endocrine therapy in early breast cancer (PALLAS): Interim analysis of a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2021;22(2):212-222. Doi: Loibl S, Marmé F, Martin M, et al. Palbociclib for residual high-risk invasive HR-positive and HER2-negative early breast cancer-The Penelope-B trial. J Clin Oncol. 2021;39(14):1518-1530. Doi: Liu X, Lu J, Wang G, et al. Acupuncture for arthralgia induced by aromatase inhibitors in patients with breast cancer: A systematic review and meta-analysis. Integr Cancer Ther. 2021;20:1534735420980811. Doi: 10.1177/1534735420980811

The risk for disease recurrence, and specifically distant relapse, for women with high-risk early breast cancer highlights the need for novel therapies in this population.^2,3 The phase 3 randomized monarchE trial investigated the role of the CDK4/6 inhibitor abemaciclib combined with endocrine therapy vs standard endocrine therapy alone in 5637 patients with high-risk (≥ 4 positive axillary nodes or 1-3 positive nodes and either grade 3 tumor, tumor size ≥ 5 cm or Ki-67 ≥ 20%) hormone receptor–positive/HER2-negative early breast cancer. At a median follow-up of 42 months, the median invasive disease-free survival (iDFS) benefit was sustained with abemaciclib + endocrine therapy vs endocrine therapy alone (HR 0.664; nominal P < .0001); the absolute 4-year iDFS benefit was 6.4% (85.8% in the abemaciclib + endocrine therapy group vs 79.4% in the endocrine therapy–alone group). Furthermore, this effect appeared to deepen over time, as the previous absolute iDFS differences were 2.8% (2 years) and 4.8% (3 years). Abemaciclib was associated with a higher rate of grade 3 or higher adverse events (49.9% vs 16.9%), the most common being neutropenia, leukopenia, and diarrhea (Johnston et al). Although adjuvant palbociclib trials (PALLAS⁴ and PENELOPE-B⁵) did not meet their primary endpoint, longer follow-up of monarchE and results from NATALEE with ribociclib are anxiously awaited to further define the role of CDK4/6 inhibitors in this space.

Aromatase inhibitors (AI) are an integral component of treatment for hormone receptor–positive breast cancer for many women. However, joint pain and stiffness associated with these agents can affect compliance. Various management strategies, including trials of alternative AI or endocrine therapies and pharmacologic (duloxetine) and non-pharmacologic (acupuncture,⁶ exercise) modalities, have been investigated. A randomized trial including 226 women with early-stage breast cancer receiving AI therapy with baseline joint pain (Brief Pain Inventory Worst Pain [BPI-WP] item score of ≥ 3) evaluated whether true acupuncture (TA) provided a sustained reduction in pain symptoms compared with sham acupuncture (SA) or waiting-list control (WC). Acupuncture protocols consisted of 6 weeks of intervention (2 sessions per week) followed by 1 session per week for another 6 weeks. At 52 weeks, mean BPI-WP scores were 1.08 points lower in the TA group compared with the SA group (P = .01) and were 0.99 points lower in the TA group compared with the WC group (P = .03) (Hershman et al). These data support consideration of acupuncture as a mechanism to help maintain patients on aromatase inhibitors, particularly for patients who wish to avoid or have not received benefit from pharmacologic therapy.

Additional References

1. Puglisi F, Gerratana L, Lambertini M, et al. Composite risk and benefit from adjuvant dose-dense chemotherapy in hormone receptor-positive breast cancer. NPJ Breast Cancer. 2021;7:82. Doi: 10.1038/s41523-021-00286-w
2. Salvo EM, Ramirez AO, Cueto J, et al. Risk of recurrence among patients with HR-positive, HER2-negative, early breast cancer receiving adjuvant endocrine therapy: A systematic review and meta-analysis. Breast. 2021;57:5-17. Doi: 10.1016/j.breast.2021.02.009
3. Sheffield KM, Peachey JR, Method M, et al. A real-world US study of recurrence risks using combined clinicopathological features in HR-positive, HER2-negative early breast cancer. Future Oncol.2022;18:2667-2682. Doi: 10.2217/fon-2022-0310
4. Mayer EL, Dueck AC, Martin M, et al. Palbociclib with adjuvant endocrine therapy in early breast cancer (PALLAS): Interim analysis of a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2021;22(2):212-222. Doi: Loibl S, Marmé F, Martin M, et al. Palbociclib for residual high-risk invasive HR-positive and HER2-negative early breast cancer-The Penelope-B trial. J Clin Oncol. 2021;39(14):1518-1530. Doi: Liu X, Lu J, Wang G, et al. Acupuncture for arthralgia induced by aromatase inhibitors in patients with breast cancer: A systematic review and meta-analysis. Integr Cancer Ther. 2021;20:1534735420980811. Doi: 10.1177/1534735420980811

Key clinical point: Chronic exposure to heavy metals was not associated with an increased risk for breast cancer (BC) among never smokers in the general population.

Major finding: Serum levels of cobalt were inversely associated with the risk for BC (odds ratio 0.33; P = .033), with no association being observed between the risk for BC and exposure to other heavy metals.

Study details: Findings are from a prospective cohort study including 150 women with BC and without a smoking history and 150 matched control women without BC and smoking history.

Disclosures: This study was supported by the Tuscany Region, “Bando Ricerca Salute 2018.” The authors declared no conflicts of interest.

Source: Caini S et al. Serum heavy metals and breast cancer risk: A case-control study nested in the Florence cohort of the EPIC (European Prospective Investigation into Cancer and nutrition) study. Sci Total Environ. 2022;160568 (Dec 1). Doi: 10.1016/j.scitotenv.2022.160568

Key clinical point: Chronic exposure to heavy metals was not associated with an increased risk for breast cancer (BC) among never smokers in the general population.

Major finding: Serum levels of cobalt were inversely associated with the risk for BC (odds ratio 0.33; P = .033), with no association being observed between the risk for BC and exposure to other heavy metals.

Study details: Findings are from a prospective cohort study including 150 women with BC and without a smoking history and 150 matched control women without BC and smoking history.

Disclosures: This study was supported by the Tuscany Region, “Bando Ricerca Salute 2018.” The authors declared no conflicts of interest.

Source: Caini S et al. Serum heavy metals and breast cancer risk: A case-control study nested in the Florence cohort of the EPIC (European Prospective Investigation into Cancer and nutrition) study. Sci Total Environ. 2022;160568 (Dec 1). Doi: 10.1016/j.scitotenv.2022.160568

Key clinical point: Chronic exposure to heavy metals was not associated with an increased risk for breast cancer (BC) among never smokers in the general population.

Major finding: Serum levels of cobalt were inversely associated with the risk for BC (odds ratio 0.33; P = .033), with no association being observed between the risk for BC and exposure to other heavy metals.

Study details: Findings are from a prospective cohort study including 150 women with BC and without a smoking history and 150 matched control women without BC and smoking history.

Disclosures: This study was supported by the Tuscany Region, “Bando Ricerca Salute 2018.” The authors declared no conflicts of interest.

Source: Caini S et al. Serum heavy metals and breast cancer risk: A case-control study nested in the Florence cohort of the EPIC (European Prospective Investigation into Cancer and nutrition) study. Sci Total Environ. 2022;160568 (Dec 1). Doi: 10.1016/j.scitotenv.2022.160568