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RA: Real-world study highlights need for increased awareness of NTM in TNFi‐treated patients

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Key clinical point: Patients with seropositive rheumatoid arthritis (RA) treated with tumor necrosis factor inhibitors (TNFi) were at higher risk of developing nontuberculous mycobacterium (NTM) infection in mycobacterium tuberculosis (MTB) endemic areas.

 

Major finding: Patients with seropositive RA from an MTB endemic area, who were treated with vs. without TNFi were at a significantly higher risk for NTM infection (adjusted hazard ratio [aHR] 1.751; 95% CI 1.105-2.774), with females (aHR 2.108), patients aged 50-65 years (aHR 2.018), and patients without comorbidities (aHR 1.742; all P < .001) at higher risk of developing NTM infection after TNFi treatment.

 

Study details: This was a retrospective, population-based longitudinal cohort study including patients with seropositive RA. Of these, 1089 patients treated with TNFI were propensity-matched with 4356 untreated patients.

 

Disclosures: The study was supported by the research fund of Hanyang University, Republic of Korea. The authors declared no conflicts of interest.

 

Source: Park DW et al. The impact of tofacitinib on fatigue, sleep, and health-related quality of life in patients with rheumatoid arthritis: a post hoc analysis of data from Phase 3 trials. Sci Rep. 2022;12:4003 (Mar 7). Doi: 10.1038/s41598-022-07968-w

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Key clinical point: Patients with seropositive rheumatoid arthritis (RA) treated with tumor necrosis factor inhibitors (TNFi) were at higher risk of developing nontuberculous mycobacterium (NTM) infection in mycobacterium tuberculosis (MTB) endemic areas.

 

Major finding: Patients with seropositive RA from an MTB endemic area, who were treated with vs. without TNFi were at a significantly higher risk for NTM infection (adjusted hazard ratio [aHR] 1.751; 95% CI 1.105-2.774), with females (aHR 2.108), patients aged 50-65 years (aHR 2.018), and patients without comorbidities (aHR 1.742; all P < .001) at higher risk of developing NTM infection after TNFi treatment.

 

Study details: This was a retrospective, population-based longitudinal cohort study including patients with seropositive RA. Of these, 1089 patients treated with TNFI were propensity-matched with 4356 untreated patients.

 

Disclosures: The study was supported by the research fund of Hanyang University, Republic of Korea. The authors declared no conflicts of interest.

 

Source: Park DW et al. The impact of tofacitinib on fatigue, sleep, and health-related quality of life in patients with rheumatoid arthritis: a post hoc analysis of data from Phase 3 trials. Sci Rep. 2022;12:4003 (Mar 7). Doi: 10.1038/s41598-022-07968-w

Key clinical point: Patients with seropositive rheumatoid arthritis (RA) treated with tumor necrosis factor inhibitors (TNFi) were at higher risk of developing nontuberculous mycobacterium (NTM) infection in mycobacterium tuberculosis (MTB) endemic areas.

 

Major finding: Patients with seropositive RA from an MTB endemic area, who were treated with vs. without TNFi were at a significantly higher risk for NTM infection (adjusted hazard ratio [aHR] 1.751; 95% CI 1.105-2.774), with females (aHR 2.108), patients aged 50-65 years (aHR 2.018), and patients without comorbidities (aHR 1.742; all P < .001) at higher risk of developing NTM infection after TNFi treatment.

 

Study details: This was a retrospective, population-based longitudinal cohort study including patients with seropositive RA. Of these, 1089 patients treated with TNFI were propensity-matched with 4356 untreated patients.

 

Disclosures: The study was supported by the research fund of Hanyang University, Republic of Korea. The authors declared no conflicts of interest.

 

Source: Park DW et al. The impact of tofacitinib on fatigue, sleep, and health-related quality of life in patients with rheumatoid arthritis: a post hoc analysis of data from Phase 3 trials. Sci Rep. 2022;12:4003 (Mar 7). Doi: 10.1038/s41598-022-07968-w

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RA: Clinically meaningful improvements in fatigue, sleep, and HRQoL with tofacitinib

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Key clinical point: Patients with rheumatoid arthritis (RA) showed greater clinically meaningful improvements in fatigue, sleep, and health-related quality of life (HRQoL) with tofacitinib vs. placebo over 6 months, with improvements sustained up to 12 months.

 

Major finding: The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) total score, Medical Outcomes Study Sleep scale (MOS-SS) Sleep Problems Index I and II scores, and Short Form-36 Health Survey (Physical/Mental Component Summary) score improved significantly with both  5 mg or 10 mg tofacitinib doses vs. placebo at months 1, 3, and 6 (all P < .05). Improvement in FACIT-F and MOS-SS scores were significantly better with 10 mg tofacitinib vs. adalimumab at 6 and 12 months (all P < .05).

 

Study details: This was a post hoc analysis of three phase 3 trials including 2265 patients with RA who received tofacitinib, placebo, or adalimumab.

 

Disclosures: This study was sponsored by Pfizer Inc. C Murray, D Gruben, and DA Gold declared being employees and stockholders of Pfizer. Some authors declared being on steering committees, boards of directors, or speakers’ bureaus or receiving consulting fees or research grants from various sources, including Pfizer.

 

Source: Bartlett SJ et al. The impact of tofacitinib on fatigue, sleep, and health-related quality of life in patients with rheumatoid arthritis: a post hoc analysis of data from phase 3 trials. Arthritis Res Ther. 2022;24:83 (Apr 5). Doi: 10.1186/s13075-022-02724-x

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Key clinical point: Patients with rheumatoid arthritis (RA) showed greater clinically meaningful improvements in fatigue, sleep, and health-related quality of life (HRQoL) with tofacitinib vs. placebo over 6 months, with improvements sustained up to 12 months.

 

Major finding: The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) total score, Medical Outcomes Study Sleep scale (MOS-SS) Sleep Problems Index I and II scores, and Short Form-36 Health Survey (Physical/Mental Component Summary) score improved significantly with both  5 mg or 10 mg tofacitinib doses vs. placebo at months 1, 3, and 6 (all P < .05). Improvement in FACIT-F and MOS-SS scores were significantly better with 10 mg tofacitinib vs. adalimumab at 6 and 12 months (all P < .05).

 

Study details: This was a post hoc analysis of three phase 3 trials including 2265 patients with RA who received tofacitinib, placebo, or adalimumab.

 

Disclosures: This study was sponsored by Pfizer Inc. C Murray, D Gruben, and DA Gold declared being employees and stockholders of Pfizer. Some authors declared being on steering committees, boards of directors, or speakers’ bureaus or receiving consulting fees or research grants from various sources, including Pfizer.

 

Source: Bartlett SJ et al. The impact of tofacitinib on fatigue, sleep, and health-related quality of life in patients with rheumatoid arthritis: a post hoc analysis of data from phase 3 trials. Arthritis Res Ther. 2022;24:83 (Apr 5). Doi: 10.1186/s13075-022-02724-x

Key clinical point: Patients with rheumatoid arthritis (RA) showed greater clinically meaningful improvements in fatigue, sleep, and health-related quality of life (HRQoL) with tofacitinib vs. placebo over 6 months, with improvements sustained up to 12 months.

 

Major finding: The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) total score, Medical Outcomes Study Sleep scale (MOS-SS) Sleep Problems Index I and II scores, and Short Form-36 Health Survey (Physical/Mental Component Summary) score improved significantly with both  5 mg or 10 mg tofacitinib doses vs. placebo at months 1, 3, and 6 (all P < .05). Improvement in FACIT-F and MOS-SS scores were significantly better with 10 mg tofacitinib vs. adalimumab at 6 and 12 months (all P < .05).

 

Study details: This was a post hoc analysis of three phase 3 trials including 2265 patients with RA who received tofacitinib, placebo, or adalimumab.

 

Disclosures: This study was sponsored by Pfizer Inc. C Murray, D Gruben, and DA Gold declared being employees and stockholders of Pfizer. Some authors declared being on steering committees, boards of directors, or speakers’ bureaus or receiving consulting fees or research grants from various sources, including Pfizer.

 

Source: Bartlett SJ et al. The impact of tofacitinib on fatigue, sleep, and health-related quality of life in patients with rheumatoid arthritis: a post hoc analysis of data from phase 3 trials. Arthritis Res Ther. 2022;24:83 (Apr 5). Doi: 10.1186/s13075-022-02724-x

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Maternal RA tied to increased risk for mental disorders in their children

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Key clinical point: Children of mothers, but not fathers, with rheumatoid arthritis (RA) were predisposed to the risk of developing multiple mental disorders.

 

Major finding: Children of mothers with RA had a significantly higher risk for autism spectrum disorders (odds ratio [OR] 1.49; 95% CI 1.01-2.20), bipolar disorder (OR 1.47; 95% CI 1.20-1.81), attention-deficit/hyperactivity disorder (OR 1.37; 95% CI 1.17-1.60), and major depressive disorder (OR 1.20; 95% CI 1.05-1.37), with no risk for these disorders observed in children of fathers with RA.

 

Study details: This was a retrospective cohort study including 23,981 RA-parent-child pairs and age-/sex-matched 239,810 non-RA-parent-child pairs.

 

Disclosures: This study received research grants from Taipei Veterans General Hospital, Yen

Tjing Ling Medical Foundation, and the Ministry of Science and Technology, Taiwan. The authors declared no conflicts of interest.

 

Source: Chiu HJ et al. A nationwide study of the risks of major mental disorders among the offspring of parents with rheumatoid arthritis. Sci Rep. 2022;12:4962 (Mar 23). Doi: 10.1038/s41598-022-08834-5

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Key clinical point: Children of mothers, but not fathers, with rheumatoid arthritis (RA) were predisposed to the risk of developing multiple mental disorders.

 

Major finding: Children of mothers with RA had a significantly higher risk for autism spectrum disorders (odds ratio [OR] 1.49; 95% CI 1.01-2.20), bipolar disorder (OR 1.47; 95% CI 1.20-1.81), attention-deficit/hyperactivity disorder (OR 1.37; 95% CI 1.17-1.60), and major depressive disorder (OR 1.20; 95% CI 1.05-1.37), with no risk for these disorders observed in children of fathers with RA.

 

Study details: This was a retrospective cohort study including 23,981 RA-parent-child pairs and age-/sex-matched 239,810 non-RA-parent-child pairs.

 

Disclosures: This study received research grants from Taipei Veterans General Hospital, Yen

Tjing Ling Medical Foundation, and the Ministry of Science and Technology, Taiwan. The authors declared no conflicts of interest.

 

Source: Chiu HJ et al. A nationwide study of the risks of major mental disorders among the offspring of parents with rheumatoid arthritis. Sci Rep. 2022;12:4962 (Mar 23). Doi: 10.1038/s41598-022-08834-5

Key clinical point: Children of mothers, but not fathers, with rheumatoid arthritis (RA) were predisposed to the risk of developing multiple mental disorders.

 

Major finding: Children of mothers with RA had a significantly higher risk for autism spectrum disorders (odds ratio [OR] 1.49; 95% CI 1.01-2.20), bipolar disorder (OR 1.47; 95% CI 1.20-1.81), attention-deficit/hyperactivity disorder (OR 1.37; 95% CI 1.17-1.60), and major depressive disorder (OR 1.20; 95% CI 1.05-1.37), with no risk for these disorders observed in children of fathers with RA.

 

Study details: This was a retrospective cohort study including 23,981 RA-parent-child pairs and age-/sex-matched 239,810 non-RA-parent-child pairs.

 

Disclosures: This study received research grants from Taipei Veterans General Hospital, Yen

Tjing Ling Medical Foundation, and the Ministry of Science and Technology, Taiwan. The authors declared no conflicts of interest.

 

Source: Chiu HJ et al. A nationwide study of the risks of major mental disorders among the offspring of parents with rheumatoid arthritis. Sci Rep. 2022;12:4962 (Mar 23). Doi: 10.1038/s41598-022-08834-5

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Rheumatoid arthritis tied to increased risk of developing primary open-angle glaucoma

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Key clinical point: Patients with seropositive rheumatoid arthritis (RA) were at a higher risk of developing primary open-angle glaucoma (POAG) compared with matched control participants, with risk being evident within 2 years after RA diagnosis and among patients aged 75 years.

 

Major finding: Compared with matched control participants, patients with incident RA were 1.44 times more likely to develop POAG (hazard ratio [HR] 1.44; 95% CI 1.13-1.84), which was predominantly observed within 2 years of RA diagnosis (HR 1.83; 95% CI 1.28-2.61) and in patients aged ≥75 years (HR 2.12;95% CI 1.34-3.35).

 

Study details: This was a retrospective, nationwide cohort study including 2049 patients with seropositive RA who were propensity score-matched with 8196 control participants without RA.

 

Disclosures: This study was partly supported by the publication fee from the Graduate School of Public Health, Yonsei University. No conflicts of interest were declared.

 

Source: Kim SH et al. Development of open-angle glaucoma in adults with seropositive rheumatoid arthritis in Korea. JAMA Netw Open. 2022;5(3):e223345 (Mar 21). Doi:  10.1001/jamanetworkopen.2022.3345

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Key clinical point: Patients with seropositive rheumatoid arthritis (RA) were at a higher risk of developing primary open-angle glaucoma (POAG) compared with matched control participants, with risk being evident within 2 years after RA diagnosis and among patients aged 75 years.

 

Major finding: Compared with matched control participants, patients with incident RA were 1.44 times more likely to develop POAG (hazard ratio [HR] 1.44; 95% CI 1.13-1.84), which was predominantly observed within 2 years of RA diagnosis (HR 1.83; 95% CI 1.28-2.61) and in patients aged ≥75 years (HR 2.12;95% CI 1.34-3.35).

 

Study details: This was a retrospective, nationwide cohort study including 2049 patients with seropositive RA who were propensity score-matched with 8196 control participants without RA.

 

Disclosures: This study was partly supported by the publication fee from the Graduate School of Public Health, Yonsei University. No conflicts of interest were declared.

 

Source: Kim SH et al. Development of open-angle glaucoma in adults with seropositive rheumatoid arthritis in Korea. JAMA Netw Open. 2022;5(3):e223345 (Mar 21). Doi:  10.1001/jamanetworkopen.2022.3345

Key clinical point: Patients with seropositive rheumatoid arthritis (RA) were at a higher risk of developing primary open-angle glaucoma (POAG) compared with matched control participants, with risk being evident within 2 years after RA diagnosis and among patients aged 75 years.

 

Major finding: Compared with matched control participants, patients with incident RA were 1.44 times more likely to develop POAG (hazard ratio [HR] 1.44; 95% CI 1.13-1.84), which was predominantly observed within 2 years of RA diagnosis (HR 1.83; 95% CI 1.28-2.61) and in patients aged ≥75 years (HR 2.12;95% CI 1.34-3.35).

 

Study details: This was a retrospective, nationwide cohort study including 2049 patients with seropositive RA who were propensity score-matched with 8196 control participants without RA.

 

Disclosures: This study was partly supported by the publication fee from the Graduate School of Public Health, Yonsei University. No conflicts of interest were declared.

 

Source: Kim SH et al. Development of open-angle glaucoma in adults with seropositive rheumatoid arthritis in Korea. JAMA Netw Open. 2022;5(3):e223345 (Mar 21). Doi:  10.1001/jamanetworkopen.2022.3345

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Controlling inflammation may not alleviate disability in all patients with RA

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Key clinical point: Some patients with rheumatoid arthritis (RA) had excess disability despite low inflammation level. This persisted over 8-10 years after onset, with age, pain, and depression being significant predictors of disability, independent of inflammation.

 

Major finding: Nearly 30%-45% of patients with RA persistently showed excess disability over 8-10 years of follow-up, independent of their inflammation status. Patients who were older (odds ratio [OR] 1.05; 95% CI 1.02-1.09) or had higher pain (OR 1.48; 95% CI 1.23-1.78) or depression (OR 1.40; 95% CI 1.01-1.94) were more likely to have higher vs. lower disability trajectory, irrespective of their inflammation level.

 

Study details: Findings are from an analysis of three cohort studies including 2500 patients with RA and <24 months symptom duration who were followed-up for 8-10 years.

 

Disclosures: This study was supported by the UK Medical Research Council, Versus Arthritis, UK National Institute for Health Care and Research (NIHR) Manchester Biomedical Research Centre, and NIHR Nottingham Biomedical Research Centre. The authors declared no competing interests directly relevant to this manuscript.

 

Source: Gwinnutt JM et al. Exploring the disparity between inflammation and disability in the 10-year outcomes of people with rheumatoid arthritis. Rheumatology (Oxford). 2022 (Mar 11). Doi: 10.1093/rheumatology/keac137

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Key clinical point: Some patients with rheumatoid arthritis (RA) had excess disability despite low inflammation level. This persisted over 8-10 years after onset, with age, pain, and depression being significant predictors of disability, independent of inflammation.

 

Major finding: Nearly 30%-45% of patients with RA persistently showed excess disability over 8-10 years of follow-up, independent of their inflammation status. Patients who were older (odds ratio [OR] 1.05; 95% CI 1.02-1.09) or had higher pain (OR 1.48; 95% CI 1.23-1.78) or depression (OR 1.40; 95% CI 1.01-1.94) were more likely to have higher vs. lower disability trajectory, irrespective of their inflammation level.

 

Study details: Findings are from an analysis of three cohort studies including 2500 patients with RA and <24 months symptom duration who were followed-up for 8-10 years.

 

Disclosures: This study was supported by the UK Medical Research Council, Versus Arthritis, UK National Institute for Health Care and Research (NIHR) Manchester Biomedical Research Centre, and NIHR Nottingham Biomedical Research Centre. The authors declared no competing interests directly relevant to this manuscript.

 

Source: Gwinnutt JM et al. Exploring the disparity between inflammation and disability in the 10-year outcomes of people with rheumatoid arthritis. Rheumatology (Oxford). 2022 (Mar 11). Doi: 10.1093/rheumatology/keac137

Key clinical point: Some patients with rheumatoid arthritis (RA) had excess disability despite low inflammation level. This persisted over 8-10 years after onset, with age, pain, and depression being significant predictors of disability, independent of inflammation.

 

Major finding: Nearly 30%-45% of patients with RA persistently showed excess disability over 8-10 years of follow-up, independent of their inflammation status. Patients who were older (odds ratio [OR] 1.05; 95% CI 1.02-1.09) or had higher pain (OR 1.48; 95% CI 1.23-1.78) or depression (OR 1.40; 95% CI 1.01-1.94) were more likely to have higher vs. lower disability trajectory, irrespective of their inflammation level.

 

Study details: Findings are from an analysis of three cohort studies including 2500 patients with RA and <24 months symptom duration who were followed-up for 8-10 years.

 

Disclosures: This study was supported by the UK Medical Research Council, Versus Arthritis, UK National Institute for Health Care and Research (NIHR) Manchester Biomedical Research Centre, and NIHR Nottingham Biomedical Research Centre. The authors declared no competing interests directly relevant to this manuscript.

 

Source: Gwinnutt JM et al. Exploring the disparity between inflammation and disability in the 10-year outcomes of people with rheumatoid arthritis. Rheumatology (Oxford). 2022 (Mar 11). Doi: 10.1093/rheumatology/keac137

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Reasons for b/tsDMARD treatment interruptions in rheumatoid arthritis

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Key clinical point: A majority of patients with rheumatoid arthritis (RA) stopped their first-time biological or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) because of nonresponse to the treatment. Patients who stopped because of remission vs. nonresponse had worse disease activity at treatment restart.

 

Major finding: Nonresponse (38%), adverse events (19%), and remission (8%) were the major reasons to stop the first-time b/tsDMARD, with the median time to restart treatment being shortest among patients with nonresponse (30 days) and longest among those with remission (1597 days). Moreover, RA disease activity was worse at b/tsDMARD restart in patients who stopped b/tsDMARD after achieving remission (P < .0001).

 

Study details: This was an explorative descriptive cohort study including 2526 patients with RA who stopped their first b/tsDMARD treatment.

 

Disclosures: The study did not declare any source of funding. No conflicts of interest were declared.

 

Source: Burkard T et al. Interruptions of biological and targeted synthetic disease-modifying antirheumatic drugs in rheumatoid arthritis: a descriptive cohort study assessing trends in patient characteristics in Switzerland. BMJ Open. 2022;12:e056352 (Mar 15). Doi: 10.1136/bmjopen-2021-056352

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Key clinical point: A majority of patients with rheumatoid arthritis (RA) stopped their first-time biological or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) because of nonresponse to the treatment. Patients who stopped because of remission vs. nonresponse had worse disease activity at treatment restart.

 

Major finding: Nonresponse (38%), adverse events (19%), and remission (8%) were the major reasons to stop the first-time b/tsDMARD, with the median time to restart treatment being shortest among patients with nonresponse (30 days) and longest among those with remission (1597 days). Moreover, RA disease activity was worse at b/tsDMARD restart in patients who stopped b/tsDMARD after achieving remission (P < .0001).

 

Study details: This was an explorative descriptive cohort study including 2526 patients with RA who stopped their first b/tsDMARD treatment.

 

Disclosures: The study did not declare any source of funding. No conflicts of interest were declared.

 

Source: Burkard T et al. Interruptions of biological and targeted synthetic disease-modifying antirheumatic drugs in rheumatoid arthritis: a descriptive cohort study assessing trends in patient characteristics in Switzerland. BMJ Open. 2022;12:e056352 (Mar 15). Doi: 10.1136/bmjopen-2021-056352

Key clinical point: A majority of patients with rheumatoid arthritis (RA) stopped their first-time biological or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) because of nonresponse to the treatment. Patients who stopped because of remission vs. nonresponse had worse disease activity at treatment restart.

 

Major finding: Nonresponse (38%), adverse events (19%), and remission (8%) were the major reasons to stop the first-time b/tsDMARD, with the median time to restart treatment being shortest among patients with nonresponse (30 days) and longest among those with remission (1597 days). Moreover, RA disease activity was worse at b/tsDMARD restart in patients who stopped b/tsDMARD after achieving remission (P < .0001).

 

Study details: This was an explorative descriptive cohort study including 2526 patients with RA who stopped their first b/tsDMARD treatment.

 

Disclosures: The study did not declare any source of funding. No conflicts of interest were declared.

 

Source: Burkard T et al. Interruptions of biological and targeted synthetic disease-modifying antirheumatic drugs in rheumatoid arthritis: a descriptive cohort study assessing trends in patient characteristics in Switzerland. BMJ Open. 2022;12:e056352 (Mar 15). Doi: 10.1136/bmjopen-2021-056352

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Elevated adipokine levels predict early death in RA

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Key clinical point: Higher levels of circulating adiponectin and leptin were associated with an increased risk for all-cause and cardiovascular mortality in patients with rheumatoid arthritis (RA).

 

Major finding: Patients in the highest vs. lowest quartile of adiponectin were at a 46% higher risk for all-cause mortality (hazard ratio [HR] 1.46; P = .009) and an 85% higher risk for cardiovascular mortality (HR 1.85; P = .003). Patients in the highest vs. lowest quartile of both adiponectin and leptin were at a 73% higher risk for all-cause mortality (HR 1.73; P = .002).

 

Study details: This was a longitudinal study including 2583 patients with RA.

 

Disclosures: This study did not declare any source of funding. JF Baker and TR MIkuls reported receiving consulting fees and research support from various sources.

 

Source: Baker JF et al. Elevations in adipocytokines and mortality in rheumatoid arthritis. Rheumatology (Oxford). 2022 Mar 23. Doi: 10.1093/rheumatology/keac191

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Key clinical point: Higher levels of circulating adiponectin and leptin were associated with an increased risk for all-cause and cardiovascular mortality in patients with rheumatoid arthritis (RA).

 

Major finding: Patients in the highest vs. lowest quartile of adiponectin were at a 46% higher risk for all-cause mortality (hazard ratio [HR] 1.46; P = .009) and an 85% higher risk for cardiovascular mortality (HR 1.85; P = .003). Patients in the highest vs. lowest quartile of both adiponectin and leptin were at a 73% higher risk for all-cause mortality (HR 1.73; P = .002).

 

Study details: This was a longitudinal study including 2583 patients with RA.

 

Disclosures: This study did not declare any source of funding. JF Baker and TR MIkuls reported receiving consulting fees and research support from various sources.

 

Source: Baker JF et al. Elevations in adipocytokines and mortality in rheumatoid arthritis. Rheumatology (Oxford). 2022 Mar 23. Doi: 10.1093/rheumatology/keac191

Key clinical point: Higher levels of circulating adiponectin and leptin were associated with an increased risk for all-cause and cardiovascular mortality in patients with rheumatoid arthritis (RA).

 

Major finding: Patients in the highest vs. lowest quartile of adiponectin were at a 46% higher risk for all-cause mortality (hazard ratio [HR] 1.46; P = .009) and an 85% higher risk for cardiovascular mortality (HR 1.85; P = .003). Patients in the highest vs. lowest quartile of both adiponectin and leptin were at a 73% higher risk for all-cause mortality (HR 1.73; P = .002).

 

Study details: This was a longitudinal study including 2583 patients with RA.

 

Disclosures: This study did not declare any source of funding. JF Baker and TR MIkuls reported receiving consulting fees and research support from various sources.

 

Source: Baker JF et al. Elevations in adipocytokines and mortality in rheumatoid arthritis. Rheumatology (Oxford). 2022 Mar 23. Doi: 10.1093/rheumatology/keac191

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Frailty is dynamic and responsive to treatment in early RA

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Key clinical point: Frailty may be partially reversible with treatment in early rheumatoid arthritis (RA) and is associated with a greater risk for hospitalization and all-cause mortality in early and established RA.

 

Major finding: Patients with early RA improved from moderate/severe frailty to mild (33%) and robust (13%) states in the first 6 months of treatment with disease-modifying antirheumatic drugs. In early and established RA, the moderate/severe vs. robust frailty level was associated with unscheduled hospitalization (incidence rate ratio [IRR] 2.88; 95% CI 1.97-4.20, and IRR 2.74; 95% CI 2.29-3.29, respectively) and all-cause mortality (hazard ratio [HR] 4.41; 95% CI 1.85-10.49 and HR 1.68; 95% CI 1.26-2.13, respectively).

 

Study details: This was a longitudinal analysis of two cohorts including 899 and 3605 patients with early and established RA, respectively.

 

Disclosures: No information on funding was reported. No conflicts of interest were declared.

 

Source: Hanlon P et al. Frailty in rheumatoid arthritis and its relationship with disease activity, hospitalisation and mortality: a longitudinal analysis of the Scottish Early Rheumatoid Arthritis cohort and UK Biobank. RMD Open. 2022;8:e002111 (Mar 15). Doi: 10.1136/rmdopen-2021-002111

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Key clinical point: Frailty may be partially reversible with treatment in early rheumatoid arthritis (RA) and is associated with a greater risk for hospitalization and all-cause mortality in early and established RA.

 

Major finding: Patients with early RA improved from moderate/severe frailty to mild (33%) and robust (13%) states in the first 6 months of treatment with disease-modifying antirheumatic drugs. In early and established RA, the moderate/severe vs. robust frailty level was associated with unscheduled hospitalization (incidence rate ratio [IRR] 2.88; 95% CI 1.97-4.20, and IRR 2.74; 95% CI 2.29-3.29, respectively) and all-cause mortality (hazard ratio [HR] 4.41; 95% CI 1.85-10.49 and HR 1.68; 95% CI 1.26-2.13, respectively).

 

Study details: This was a longitudinal analysis of two cohorts including 899 and 3605 patients with early and established RA, respectively.

 

Disclosures: No information on funding was reported. No conflicts of interest were declared.

 

Source: Hanlon P et al. Frailty in rheumatoid arthritis and its relationship with disease activity, hospitalisation and mortality: a longitudinal analysis of the Scottish Early Rheumatoid Arthritis cohort and UK Biobank. RMD Open. 2022;8:e002111 (Mar 15). Doi: 10.1136/rmdopen-2021-002111

Key clinical point: Frailty may be partially reversible with treatment in early rheumatoid arthritis (RA) and is associated with a greater risk for hospitalization and all-cause mortality in early and established RA.

 

Major finding: Patients with early RA improved from moderate/severe frailty to mild (33%) and robust (13%) states in the first 6 months of treatment with disease-modifying antirheumatic drugs. In early and established RA, the moderate/severe vs. robust frailty level was associated with unscheduled hospitalization (incidence rate ratio [IRR] 2.88; 95% CI 1.97-4.20, and IRR 2.74; 95% CI 2.29-3.29, respectively) and all-cause mortality (hazard ratio [HR] 4.41; 95% CI 1.85-10.49 and HR 1.68; 95% CI 1.26-2.13, respectively).

 

Study details: This was a longitudinal analysis of two cohorts including 899 and 3605 patients with early and established RA, respectively.

 

Disclosures: No information on funding was reported. No conflicts of interest were declared.

 

Source: Hanlon P et al. Frailty in rheumatoid arthritis and its relationship with disease activity, hospitalisation and mortality: a longitudinal analysis of the Scottish Early Rheumatoid Arthritis cohort and UK Biobank. RMD Open. 2022;8:e002111 (Mar 15). Doi: 10.1136/rmdopen-2021-002111

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RA: Dosage and timing of rituximab infusion influence response to COVID-19 vaccine

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Key clinical point: An ultralow dose (200 mg) of rituximab infusion and an increased time interval between COVID-19 vaccination and rituximab infusion significantly improved humoral response to COVID-19 vaccine in patients with rheumatoid arthritis (RA).

 

Major finding: Positive vaccination response was more frequently observed in the 200 mg vs. 1000 mg rituximab infusion group (odds ratio [OR] 3.07; P = .03) and improved with greater time interval between rituximab infusion and COVID-19 vaccination (per month OR 1.67; P < .0001).

 

Study details: This was a prospective cohort study, RTX-COVAC, including 196 patients with RA who received at least one dose of rituximab (200, 500, or 1000 mg) in the year prior to their first dose of COVID-19 vaccination.

 

Disclosures: This study did not receive any specific funding. AA den Broeder reported receiving personal fees, congress invitations, and grants outside the submitted work from various sources. Other authors declared no conflicts of interest.

 

Source: van der Togt CJT et al. Humoral response to Coronavirus Disease-19 vaccines is dependent on dosage and timing of rituximab in patients with rheumatoid arthritis. Rheumatology (Oxford). 2022 (Apr 4). Doi: 10.1093/rheumatology/keac206

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Key clinical point: An ultralow dose (200 mg) of rituximab infusion and an increased time interval between COVID-19 vaccination and rituximab infusion significantly improved humoral response to COVID-19 vaccine in patients with rheumatoid arthritis (RA).

 

Major finding: Positive vaccination response was more frequently observed in the 200 mg vs. 1000 mg rituximab infusion group (odds ratio [OR] 3.07; P = .03) and improved with greater time interval between rituximab infusion and COVID-19 vaccination (per month OR 1.67; P < .0001).

 

Study details: This was a prospective cohort study, RTX-COVAC, including 196 patients with RA who received at least one dose of rituximab (200, 500, or 1000 mg) in the year prior to their first dose of COVID-19 vaccination.

 

Disclosures: This study did not receive any specific funding. AA den Broeder reported receiving personal fees, congress invitations, and grants outside the submitted work from various sources. Other authors declared no conflicts of interest.

 

Source: van der Togt CJT et al. Humoral response to Coronavirus Disease-19 vaccines is dependent on dosage and timing of rituximab in patients with rheumatoid arthritis. Rheumatology (Oxford). 2022 (Apr 4). Doi: 10.1093/rheumatology/keac206

Key clinical point: An ultralow dose (200 mg) of rituximab infusion and an increased time interval between COVID-19 vaccination and rituximab infusion significantly improved humoral response to COVID-19 vaccine in patients with rheumatoid arthritis (RA).

 

Major finding: Positive vaccination response was more frequently observed in the 200 mg vs. 1000 mg rituximab infusion group (odds ratio [OR] 3.07; P = .03) and improved with greater time interval between rituximab infusion and COVID-19 vaccination (per month OR 1.67; P < .0001).

 

Study details: This was a prospective cohort study, RTX-COVAC, including 196 patients with RA who received at least one dose of rituximab (200, 500, or 1000 mg) in the year prior to their first dose of COVID-19 vaccination.

 

Disclosures: This study did not receive any specific funding. AA den Broeder reported receiving personal fees, congress invitations, and grants outside the submitted work from various sources. Other authors declared no conflicts of interest.

 

Source: van der Togt CJT et al. Humoral response to Coronavirus Disease-19 vaccines is dependent on dosage and timing of rituximab in patients with rheumatoid arthritis. Rheumatology (Oxford). 2022 (Apr 4). Doi: 10.1093/rheumatology/keac206

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Long-term efficacy, safety data for ixekizumab in pediatric psoriasis reported

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Two-year follow-up data from an international, multicenter, randomized trial of ixekizumab in pediatric patients with moderate to severe psoriasis demonstrate prolonged efficacy and no new safety signals with the interleukin (IL)-17 inhibitor, investigators reported.

In addition, findings of a substudy, which evaluated randomized withdrawal of treatment after 60 weeks, suggest patients were able to regain benefit after not being treated for a period.

Ixekizumab (Taltz) was approved by the U.S. Food and Drug Administration for treating pediatric psoriasis in March 2020 for patients aged 6 years and older with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy.

The trial (IXORA-PEDS) involved 171 patients aged 6-17 years (mean age, 13.5 years; 99 females and 72 males), who were randomly assigned to receive ixekizumab via subcutaneous administration every 4 weeks (115) or placebo for 12 weeks (56). Thereafter, 166 patients continued in an open-label maintenance period in which they were treated every 4 weeks for 12-60 weeks. This was followed by an extension period of up to 108 weeks, which was completed by 139 patients (83.7%). At baseline, the patients’ Psoriasis Area and Severity Index (PASI) score was 12 or higher, the static Physician’s Global Assessment (sPGA) score was 3 or higher, and 10% or more of body surface area was affected.



In the study, at 12 weeks, treatment with ixekizumab was superior to placebo, with sustained responses through 48 weeks. In the follow-up phase, primary and secondary endpoints were sustained through week 108, with patients achieving or maintaining PASI 75 (91.7%), PASI 90 (79%), PASI 100 (55.1%), sPGA 0 or 1 (78.3%), and sPGA 0 (52.4%). Significant improvements in itch were seen at 12 weeks and were sustained with “meaningful improvements in itch for 78.5% of these patients at week 108,” the investigators report.

Among the patients who received ixekizumab, clearance rates in areas that are difficult to treat increased from week 12 to week 108 among those affected. During this time, clearance of nail psoriasis increased from 22.8% to 68.1%, clearance of palmoplantar psoriasis increased from 46.2% to 90%, clearance of scalp psoriasis increased from 70.7% to 76.2%, and clearance of genital psoriasis increased from 83.3% to 87.5%.

No new safety findings during weeks 48-108 of the trial were reported, including no new cases of inflammatory bowel disease (IBD) or Candida infections. The results were reported in JAMA Dermatology.

“Safety is really what we think of most when we are talking about pediatric patients, especially since they may be on these for decades and ... since they most commonly start these therapies in adolescence,” said Amy Paller, MD, the study’s lead author, in an interview. “To be able to take this out 108 weeks, 2 years, is starting to get to a point where we are getting more comfortable with safety. Clearly, no new signals arose.” Dr. Paller is chair of the department of dermatology and professor of dermatology and pediatrics, Northwestern University, Chicago.

Dr. Amy S. Paller


One of the biggest concerns with using IL-17 inhibitors such as ixekizumab to manage psoriasis is the development of IBD, said Dr. Paller. She noted that four cases of IBD were reported before the extension phase of the trial but that no new IBD cases were reported after week 48.

“We would not start this as a treatment of choice in someone with Crohn’s disease, or perhaps we would think twice about using it in someone with a strong family history [of Crohn’s disease],” said Dr. Paller, who is also the director of the Skin Biology and Diseases Resource-Based Center at Northwestern. “Otherwise, it does not make me concerned about its use.”

Commenting on the study, Kelly M. Cordoro, MD, professor of dermatology and pediatrics at the University of California, San Francisco, said that the trial’s results provide additional evidence regarding the optimal management of pediatric psoriasis.

Dr. Kelly M. Cordoro


“The landscape has shifted toward involving more pediatric patients in clinical trials, thereby providing dermatologists with data to select safe and effective therapies to manage children with psoriasis,” Dr. Cordoro said in an interview. “We have data showing that children with psoriasis have been undertreated, likely because of concerns about safety. The more evidence available from trials such as this, the more likely children are to receive necessary treatment.”

The efficacy data from the study on difficult-to-treat areas of psoriasis, in addition to improvements in BSA and PASI measures, are significant for clinicians deciding on a therapy for patients with psoriasis concentrated in specific body sites. “It was very valuable that the efficacy data was provided by site, such as scalp, palmoplantar, nails, and genital psoriasis, as these are low-BSA but high-impact areas for patients,” said Dr. Cordoro.

The trial data on Crohn’s disease buttress her decision to continue to refrain from initiating ixekizumab in a child with IBD or who is at high risk for IBD. “I was happy to see that there was not a signal for Candida infection,” she added.

Interestingly, in the substudy in the European population, in which there was a double-blind, randomized withdrawal period, fewer patients who were reassigned to receive ixekizumab experienced relapse, compared with those who were reassigned to receive placebo. A total of 90.9% of patients who received placebo experienced relapse, compared with 17.6% of patients treated with ixekizumab. The median time to relapse in the placebo group was 149 days.

“There are data in the adult population that suggest intermittent treatment does allow for recapture of clinical response,” said Dr. Cordoro. “While it is not a large enough dataset to know definitively, this substudy of patients suggests the possibility of intermittent treatment and the ability to regain control [of psoriasis] after a period off drug.”

The study was funded by Eli Lilly. Dr. Paller is an investigator and consultant for Eli Lilly. Several other authors have received grants, personal fees, and/or were a consultant to Eli Lilly, and two authors are Eli Lilly employees. Dr. Cordoro reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

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Two-year follow-up data from an international, multicenter, randomized trial of ixekizumab in pediatric patients with moderate to severe psoriasis demonstrate prolonged efficacy and no new safety signals with the interleukin (IL)-17 inhibitor, investigators reported.

In addition, findings of a substudy, which evaluated randomized withdrawal of treatment after 60 weeks, suggest patients were able to regain benefit after not being treated for a period.

Ixekizumab (Taltz) was approved by the U.S. Food and Drug Administration for treating pediatric psoriasis in March 2020 for patients aged 6 years and older with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy.

The trial (IXORA-PEDS) involved 171 patients aged 6-17 years (mean age, 13.5 years; 99 females and 72 males), who were randomly assigned to receive ixekizumab via subcutaneous administration every 4 weeks (115) or placebo for 12 weeks (56). Thereafter, 166 patients continued in an open-label maintenance period in which they were treated every 4 weeks for 12-60 weeks. This was followed by an extension period of up to 108 weeks, which was completed by 139 patients (83.7%). At baseline, the patients’ Psoriasis Area and Severity Index (PASI) score was 12 or higher, the static Physician’s Global Assessment (sPGA) score was 3 or higher, and 10% or more of body surface area was affected.



In the study, at 12 weeks, treatment with ixekizumab was superior to placebo, with sustained responses through 48 weeks. In the follow-up phase, primary and secondary endpoints were sustained through week 108, with patients achieving or maintaining PASI 75 (91.7%), PASI 90 (79%), PASI 100 (55.1%), sPGA 0 or 1 (78.3%), and sPGA 0 (52.4%). Significant improvements in itch were seen at 12 weeks and were sustained with “meaningful improvements in itch for 78.5% of these patients at week 108,” the investigators report.

Among the patients who received ixekizumab, clearance rates in areas that are difficult to treat increased from week 12 to week 108 among those affected. During this time, clearance of nail psoriasis increased from 22.8% to 68.1%, clearance of palmoplantar psoriasis increased from 46.2% to 90%, clearance of scalp psoriasis increased from 70.7% to 76.2%, and clearance of genital psoriasis increased from 83.3% to 87.5%.

No new safety findings during weeks 48-108 of the trial were reported, including no new cases of inflammatory bowel disease (IBD) or Candida infections. The results were reported in JAMA Dermatology.

“Safety is really what we think of most when we are talking about pediatric patients, especially since they may be on these for decades and ... since they most commonly start these therapies in adolescence,” said Amy Paller, MD, the study’s lead author, in an interview. “To be able to take this out 108 weeks, 2 years, is starting to get to a point where we are getting more comfortable with safety. Clearly, no new signals arose.” Dr. Paller is chair of the department of dermatology and professor of dermatology and pediatrics, Northwestern University, Chicago.

Dr. Amy S. Paller


One of the biggest concerns with using IL-17 inhibitors such as ixekizumab to manage psoriasis is the development of IBD, said Dr. Paller. She noted that four cases of IBD were reported before the extension phase of the trial but that no new IBD cases were reported after week 48.

“We would not start this as a treatment of choice in someone with Crohn’s disease, or perhaps we would think twice about using it in someone with a strong family history [of Crohn’s disease],” said Dr. Paller, who is also the director of the Skin Biology and Diseases Resource-Based Center at Northwestern. “Otherwise, it does not make me concerned about its use.”

Commenting on the study, Kelly M. Cordoro, MD, professor of dermatology and pediatrics at the University of California, San Francisco, said that the trial’s results provide additional evidence regarding the optimal management of pediatric psoriasis.

Dr. Kelly M. Cordoro


“The landscape has shifted toward involving more pediatric patients in clinical trials, thereby providing dermatologists with data to select safe and effective therapies to manage children with psoriasis,” Dr. Cordoro said in an interview. “We have data showing that children with psoriasis have been undertreated, likely because of concerns about safety. The more evidence available from trials such as this, the more likely children are to receive necessary treatment.”

The efficacy data from the study on difficult-to-treat areas of psoriasis, in addition to improvements in BSA and PASI measures, are significant for clinicians deciding on a therapy for patients with psoriasis concentrated in specific body sites. “It was very valuable that the efficacy data was provided by site, such as scalp, palmoplantar, nails, and genital psoriasis, as these are low-BSA but high-impact areas for patients,” said Dr. Cordoro.

The trial data on Crohn’s disease buttress her decision to continue to refrain from initiating ixekizumab in a child with IBD or who is at high risk for IBD. “I was happy to see that there was not a signal for Candida infection,” she added.

Interestingly, in the substudy in the European population, in which there was a double-blind, randomized withdrawal period, fewer patients who were reassigned to receive ixekizumab experienced relapse, compared with those who were reassigned to receive placebo. A total of 90.9% of patients who received placebo experienced relapse, compared with 17.6% of patients treated with ixekizumab. The median time to relapse in the placebo group was 149 days.

“There are data in the adult population that suggest intermittent treatment does allow for recapture of clinical response,” said Dr. Cordoro. “While it is not a large enough dataset to know definitively, this substudy of patients suggests the possibility of intermittent treatment and the ability to regain control [of psoriasis] after a period off drug.”

The study was funded by Eli Lilly. Dr. Paller is an investigator and consultant for Eli Lilly. Several other authors have received grants, personal fees, and/or were a consultant to Eli Lilly, and two authors are Eli Lilly employees. Dr. Cordoro reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Two-year follow-up data from an international, multicenter, randomized trial of ixekizumab in pediatric patients with moderate to severe psoriasis demonstrate prolonged efficacy and no new safety signals with the interleukin (IL)-17 inhibitor, investigators reported.

In addition, findings of a substudy, which evaluated randomized withdrawal of treatment after 60 weeks, suggest patients were able to regain benefit after not being treated for a period.

Ixekizumab (Taltz) was approved by the U.S. Food and Drug Administration for treating pediatric psoriasis in March 2020 for patients aged 6 years and older with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy.

The trial (IXORA-PEDS) involved 171 patients aged 6-17 years (mean age, 13.5 years; 99 females and 72 males), who were randomly assigned to receive ixekizumab via subcutaneous administration every 4 weeks (115) or placebo for 12 weeks (56). Thereafter, 166 patients continued in an open-label maintenance period in which they were treated every 4 weeks for 12-60 weeks. This was followed by an extension period of up to 108 weeks, which was completed by 139 patients (83.7%). At baseline, the patients’ Psoriasis Area and Severity Index (PASI) score was 12 or higher, the static Physician’s Global Assessment (sPGA) score was 3 or higher, and 10% or more of body surface area was affected.



In the study, at 12 weeks, treatment with ixekizumab was superior to placebo, with sustained responses through 48 weeks. In the follow-up phase, primary and secondary endpoints were sustained through week 108, with patients achieving or maintaining PASI 75 (91.7%), PASI 90 (79%), PASI 100 (55.1%), sPGA 0 or 1 (78.3%), and sPGA 0 (52.4%). Significant improvements in itch were seen at 12 weeks and were sustained with “meaningful improvements in itch for 78.5% of these patients at week 108,” the investigators report.

Among the patients who received ixekizumab, clearance rates in areas that are difficult to treat increased from week 12 to week 108 among those affected. During this time, clearance of nail psoriasis increased from 22.8% to 68.1%, clearance of palmoplantar psoriasis increased from 46.2% to 90%, clearance of scalp psoriasis increased from 70.7% to 76.2%, and clearance of genital psoriasis increased from 83.3% to 87.5%.

No new safety findings during weeks 48-108 of the trial were reported, including no new cases of inflammatory bowel disease (IBD) or Candida infections. The results were reported in JAMA Dermatology.

“Safety is really what we think of most when we are talking about pediatric patients, especially since they may be on these for decades and ... since they most commonly start these therapies in adolescence,” said Amy Paller, MD, the study’s lead author, in an interview. “To be able to take this out 108 weeks, 2 years, is starting to get to a point where we are getting more comfortable with safety. Clearly, no new signals arose.” Dr. Paller is chair of the department of dermatology and professor of dermatology and pediatrics, Northwestern University, Chicago.

Dr. Amy S. Paller


One of the biggest concerns with using IL-17 inhibitors such as ixekizumab to manage psoriasis is the development of IBD, said Dr. Paller. She noted that four cases of IBD were reported before the extension phase of the trial but that no new IBD cases were reported after week 48.

“We would not start this as a treatment of choice in someone with Crohn’s disease, or perhaps we would think twice about using it in someone with a strong family history [of Crohn’s disease],” said Dr. Paller, who is also the director of the Skin Biology and Diseases Resource-Based Center at Northwestern. “Otherwise, it does not make me concerned about its use.”

Commenting on the study, Kelly M. Cordoro, MD, professor of dermatology and pediatrics at the University of California, San Francisco, said that the trial’s results provide additional evidence regarding the optimal management of pediatric psoriasis.

Dr. Kelly M. Cordoro


“The landscape has shifted toward involving more pediatric patients in clinical trials, thereby providing dermatologists with data to select safe and effective therapies to manage children with psoriasis,” Dr. Cordoro said in an interview. “We have data showing that children with psoriasis have been undertreated, likely because of concerns about safety. The more evidence available from trials such as this, the more likely children are to receive necessary treatment.”

The efficacy data from the study on difficult-to-treat areas of psoriasis, in addition to improvements in BSA and PASI measures, are significant for clinicians deciding on a therapy for patients with psoriasis concentrated in specific body sites. “It was very valuable that the efficacy data was provided by site, such as scalp, palmoplantar, nails, and genital psoriasis, as these are low-BSA but high-impact areas for patients,” said Dr. Cordoro.

The trial data on Crohn’s disease buttress her decision to continue to refrain from initiating ixekizumab in a child with IBD or who is at high risk for IBD. “I was happy to see that there was not a signal for Candida infection,” she added.

Interestingly, in the substudy in the European population, in which there was a double-blind, randomized withdrawal period, fewer patients who were reassigned to receive ixekizumab experienced relapse, compared with those who were reassigned to receive placebo. A total of 90.9% of patients who received placebo experienced relapse, compared with 17.6% of patients treated with ixekizumab. The median time to relapse in the placebo group was 149 days.

“There are data in the adult population that suggest intermittent treatment does allow for recapture of clinical response,” said Dr. Cordoro. “While it is not a large enough dataset to know definitively, this substudy of patients suggests the possibility of intermittent treatment and the ability to regain control [of psoriasis] after a period off drug.”

The study was funded by Eli Lilly. Dr. Paller is an investigator and consultant for Eli Lilly. Several other authors have received grants, personal fees, and/or were a consultant to Eli Lilly, and two authors are Eli Lilly employees. Dr. Cordoro reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

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