Atopic Dermatitis

Key clinical point: Although food allergy (FA) is common among pediatric patients with atopic dermatitis (AD), immunoglobulin E (IgE) mediates the majority of instances and very few patients report food-triggered AD (FTAD), cautioning against unnecessary dietary restrictions.

Major finding: IgE-mediated FA was common in the overall cohort (55%) irrespective of the severity of AD (mild, 60%; moderate, 45%; severe, 57%), whereas FTAD was rare (3%) and diagnosed in only 2%, 6%, and 4% of patients with mild, moderate, and severe AD, respectively. In patients with AD only, more patients developed IgE-mediated FA vs FTAD (29% vs 5%).

Study details: Findings are from a retrospective study including 372 pediatric patients with AD, of which 29% had moderate AD and 18% had severe AD.

Disclosures: This study was funded by University of Wisconsin-Madison. The authors declared no conflicts of interest.

Source: Li JC et al. Prevalence of food allergy diagnosis in pediatric patients with atopic dermatitis referred to allergy and/or dermatology subspecialty clinics. J Allergy Clin Immunol Pract. 2022 (Jun 8). Doi: 10.1016/j.jaip.2022.05.028

Key clinical point: Although food allergy (FA) is common among pediatric patients with atopic dermatitis (AD), immunoglobulin E (IgE) mediates the majority of instances and very few patients report food-triggered AD (FTAD), cautioning against unnecessary dietary restrictions.

Major finding: IgE-mediated FA was common in the overall cohort (55%) irrespective of the severity of AD (mild, 60%; moderate, 45%; severe, 57%), whereas FTAD was rare (3%) and diagnosed in only 2%, 6%, and 4% of patients with mild, moderate, and severe AD, respectively. In patients with AD only, more patients developed IgE-mediated FA vs FTAD (29% vs 5%).

Study details: Findings are from a retrospective study including 372 pediatric patients with AD, of which 29% had moderate AD and 18% had severe AD.

Disclosures: This study was funded by University of Wisconsin-Madison. The authors declared no conflicts of interest.

Source: Li JC et al. Prevalence of food allergy diagnosis in pediatric patients with atopic dermatitis referred to allergy and/or dermatology subspecialty clinics. J Allergy Clin Immunol Pract. 2022 (Jun 8). Doi: 10.1016/j.jaip.2022.05.028

Key clinical point: Although food allergy (FA) is common among pediatric patients with atopic dermatitis (AD), immunoglobulin E (IgE) mediates the majority of instances and very few patients report food-triggered AD (FTAD), cautioning against unnecessary dietary restrictions.

Major finding: IgE-mediated FA was common in the overall cohort (55%) irrespective of the severity of AD (mild, 60%; moderate, 45%; severe, 57%), whereas FTAD was rare (3%) and diagnosed in only 2%, 6%, and 4% of patients with mild, moderate, and severe AD, respectively. In patients with AD only, more patients developed IgE-mediated FA vs FTAD (29% vs 5%).

Study details: Findings are from a retrospective study including 372 pediatric patients with AD, of which 29% had moderate AD and 18% had severe AD.

Disclosures: This study was funded by University of Wisconsin-Madison. The authors declared no conflicts of interest.

Source: Li JC et al. Prevalence of food allergy diagnosis in pediatric patients with atopic dermatitis referred to allergy and/or dermatology subspecialty clinics. J Allergy Clin Immunol Pract. 2022 (Jun 8). Doi: 10.1016/j.jaip.2022.05.028

Key clinical point: Age, sex, body mass index (BMI), onset age of atopic dermatitis (AD), smoking habits, presence of palmar hyperlinearity, and other atopic diseases determine the disease severity in patients with AD.

Major finding: Compared with patients with mild AD, those with severe AD were usually older (P  =  .020) and male (P  =  .002) with an early onset age of AD (<2 years; P  =  .004), higher BMI (P < .000), history of smoking (P  =  .012), concomitant asthma (P  =  .001), palmar hyperlinearity (P  =  .013), hand dermatitis (P  =  .020), history of contact allergy (P  =  .042), and higher immunoglobulin E levels (P < .0001).

Study details: Findings are from a single-center, cross-sectional observational study including 502 Finnish patients with AD, of which 146, 231, and 125 patients had mild, moderate, and severe AD, respectively.

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

Source: Salava A et al. Factors associated with severity of atopic dermatitis - a Finnish cross-sectional study. J Eur Acad Dermatol Venereol. 2022 (Jun 29). Doi: 10.1111/jdv.18378

Key clinical point: Age, sex, body mass index (BMI), onset age of atopic dermatitis (AD), smoking habits, presence of palmar hyperlinearity, and other atopic diseases determine the disease severity in patients with AD.

Major finding: Compared with patients with mild AD, those with severe AD were usually older (P  =  .020) and male (P  =  .002) with an early onset age of AD (<2 years; P  =  .004), higher BMI (P < .000), history of smoking (P  =  .012), concomitant asthma (P  =  .001), palmar hyperlinearity (P  =  .013), hand dermatitis (P  =  .020), history of contact allergy (P  =  .042), and higher immunoglobulin E levels (P < .0001).

Study details: Findings are from a single-center, cross-sectional observational study including 502 Finnish patients with AD, of which 146, 231, and 125 patients had mild, moderate, and severe AD, respectively.

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

Source: Salava A et al. Factors associated with severity of atopic dermatitis - a Finnish cross-sectional study. J Eur Acad Dermatol Venereol. 2022 (Jun 29). Doi: 10.1111/jdv.18378

Key clinical point: Age, sex, body mass index (BMI), onset age of atopic dermatitis (AD), smoking habits, presence of palmar hyperlinearity, and other atopic diseases determine the disease severity in patients with AD.

Major finding: Compared with patients with mild AD, those with severe AD were usually older (P  =  .020) and male (P  =  .002) with an early onset age of AD (<2 years; P  =  .004), higher BMI (P < .000), history of smoking (P  =  .012), concomitant asthma (P  =  .001), palmar hyperlinearity (P  =  .013), hand dermatitis (P  =  .020), history of contact allergy (P  =  .042), and higher immunoglobulin E levels (P < .0001).

Study details: Findings are from a single-center, cross-sectional observational study including 502 Finnish patients with AD, of which 146, 231, and 125 patients had mild, moderate, and severe AD, respectively.

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

Source: Salava A et al. Factors associated with severity of atopic dermatitis - a Finnish cross-sectional study. J Eur Acad Dermatol Venereol. 2022 (Jun 29). Doi: 10.1111/jdv.18378

Key clinical point: A 52-week long treatment with difamilast ointment was well tolerated and reduced the severity of atopic dermatitis (AD) in Japanese adult and pediatric patients.

Major finding: Overall, 72.3% of adult patients and 89.0% of pediatric patients experienced treatment-emergent adverse events (TEAE) of mostly mild or moderate severity, and only 7.8% of adult patients and 3.5% of pediatric patients discontinued treatment due to TEAE. At week 52, 55.4% of adult patients and 73.5% of pediatric patients achieved ≥75% improvement in the Eczema Area and Severity Index.

Study details: Findings are from a long-term, open-label, phase 3 study including 166 adult (15-70 years) and 200 pediatric (2-14 years) patients with AD who initiated a 52-week treatment with 0.3% or 1% difamilast ointment.

Disclosures: This study was supported by Otsuka Pharmaceutical Co., Ltd. Three authors declared being employees of Otsuka Pharmaceutical, and the other author declared receiving consulting fees, funding, grant support, and honoraria from several sources, including Otsuka Pharmaceutical.

Source: Saeki H et al. Difamilast ointment in Japanese adult and pediatric patients with atopic dermatitis: A phase III, long-term, open-label study. Dermatol Ther (Heidelb). 2022;12:1589-1601 (Jun 18). Doi: 10.1007/s13555-022-00751-9

Key clinical point: A 52-week long treatment with difamilast ointment was well tolerated and reduced the severity of atopic dermatitis (AD) in Japanese adult and pediatric patients.

Major finding: Overall, 72.3% of adult patients and 89.0% of pediatric patients experienced treatment-emergent adverse events (TEAE) of mostly mild or moderate severity, and only 7.8% of adult patients and 3.5% of pediatric patients discontinued treatment due to TEAE. At week 52, 55.4% of adult patients and 73.5% of pediatric patients achieved ≥75% improvement in the Eczema Area and Severity Index.

Study details: Findings are from a long-term, open-label, phase 3 study including 166 adult (15-70 years) and 200 pediatric (2-14 years) patients with AD who initiated a 52-week treatment with 0.3% or 1% difamilast ointment.

Disclosures: This study was supported by Otsuka Pharmaceutical Co., Ltd. Three authors declared being employees of Otsuka Pharmaceutical, and the other author declared receiving consulting fees, funding, grant support, and honoraria from several sources, including Otsuka Pharmaceutical.

Source: Saeki H et al. Difamilast ointment in Japanese adult and pediatric patients with atopic dermatitis: A phase III, long-term, open-label study. Dermatol Ther (Heidelb). 2022;12:1589-1601 (Jun 18). Doi: 10.1007/s13555-022-00751-9

Key clinical point: A 52-week long treatment with difamilast ointment was well tolerated and reduced the severity of atopic dermatitis (AD) in Japanese adult and pediatric patients.

Major finding: Overall, 72.3% of adult patients and 89.0% of pediatric patients experienced treatment-emergent adverse events (TEAE) of mostly mild or moderate severity, and only 7.8% of adult patients and 3.5% of pediatric patients discontinued treatment due to TEAE. At week 52, 55.4% of adult patients and 73.5% of pediatric patients achieved ≥75% improvement in the Eczema Area and Severity Index.

Study details: Findings are from a long-term, open-label, phase 3 study including 166 adult (15-70 years) and 200 pediatric (2-14 years) patients with AD who initiated a 52-week treatment with 0.3% or 1% difamilast ointment.

Disclosures: This study was supported by Otsuka Pharmaceutical Co., Ltd. Three authors declared being employees of Otsuka Pharmaceutical, and the other author declared receiving consulting fees, funding, grant support, and honoraria from several sources, including Otsuka Pharmaceutical.

Source: Saeki H et al. Difamilast ointment in Japanese adult and pediatric patients with atopic dermatitis: A phase III, long-term, open-label study. Dermatol Ther (Heidelb). 2022;12:1589-1601 (Jun 18). Doi: 10.1007/s13555-022-00751-9

Key clinical point: Acne caused by upadacitinib in adolescents and adults with moderate-to-severe atopic dermatitis (AD) is typically mild or moderate in severity and may not be considered a significant safety risk.

Major finding: Acne of mostly mild or moderate severity was reported by a higher proportion of patients receiving 15 mg upadacitinib (9.8%) and 30 mg upadacitinib (15.2%) vs placebo (2.2%), with no intervention required in 40.5% and 46.6% of patients receiving 15 and 30 mg upadacitinib, respectively. The improvement in quality-of-life scores was proportional to the decrease in AD severity and was similar in patients with or without acne.

Study details: Findings are from a post hoc integrated analysis of 3 phase 3 trials including 2583 patients with moderate-to-severe AD who were randomly assigned to receive upadacitinib (15 or 30 mg) or placebo as monotherapy or with concomitant topical corticosteroids.

Disclosures: This study was funded by AbbVie, Inc. Five authors declared being employees or stockholders of AbbVie. The other authors reported ties with various sources, including AbbVie.

Source: Mendes-Bastos P et al. Characterization of acne associated with upadacitinib treatment in patients with moderate-to-severe atopic dermatitis: A post hoc integrated analysis of 3 phase 3 randomized, double-blind, placebo-controlled trials. J Am Acad Dermatol. 2022 (Jun 14). Doi: 10.1016/j.jaad.2022.06.012

Key clinical point: Acne caused by upadacitinib in adolescents and adults with moderate-to-severe atopic dermatitis (AD) is typically mild or moderate in severity and may not be considered a significant safety risk.

Major finding: Acne of mostly mild or moderate severity was reported by a higher proportion of patients receiving 15 mg upadacitinib (9.8%) and 30 mg upadacitinib (15.2%) vs placebo (2.2%), with no intervention required in 40.5% and 46.6% of patients receiving 15 and 30 mg upadacitinib, respectively. The improvement in quality-of-life scores was proportional to the decrease in AD severity and was similar in patients with or without acne.

Study details: Findings are from a post hoc integrated analysis of 3 phase 3 trials including 2583 patients with moderate-to-severe AD who were randomly assigned to receive upadacitinib (15 or 30 mg) or placebo as monotherapy or with concomitant topical corticosteroids.

Disclosures: This study was funded by AbbVie, Inc. Five authors declared being employees or stockholders of AbbVie. The other authors reported ties with various sources, including AbbVie.

Source: Mendes-Bastos P et al. Characterization of acne associated with upadacitinib treatment in patients with moderate-to-severe atopic dermatitis: A post hoc integrated analysis of 3 phase 3 randomized, double-blind, placebo-controlled trials. J Am Acad Dermatol. 2022 (Jun 14). Doi: 10.1016/j.jaad.2022.06.012

Key clinical point: Acne caused by upadacitinib in adolescents and adults with moderate-to-severe atopic dermatitis (AD) is typically mild or moderate in severity and may not be considered a significant safety risk.

Major finding: Acne of mostly mild or moderate severity was reported by a higher proportion of patients receiving 15 mg upadacitinib (9.8%) and 30 mg upadacitinib (15.2%) vs placebo (2.2%), with no intervention required in 40.5% and 46.6% of patients receiving 15 and 30 mg upadacitinib, respectively. The improvement in quality-of-life scores was proportional to the decrease in AD severity and was similar in patients with or without acne.

Study details: Findings are from a post hoc integrated analysis of 3 phase 3 trials including 2583 patients with moderate-to-severe AD who were randomly assigned to receive upadacitinib (15 or 30 mg) or placebo as monotherapy or with concomitant topical corticosteroids.

Disclosures: This study was funded by AbbVie, Inc. Five authors declared being employees or stockholders of AbbVie. The other authors reported ties with various sources, including AbbVie.

Source: Mendes-Bastos P et al. Characterization of acne associated with upadacitinib treatment in patients with moderate-to-severe atopic dermatitis: A post hoc integrated analysis of 3 phase 3 randomized, double-blind, placebo-controlled trials. J Am Acad Dermatol. 2022 (Jun 14). Doi: 10.1016/j.jaad.2022.06.012

Key clinical point: Dupilumab was more effective than topical corticosteroids (TCS) and cyclosporine in reducing the severity of atopic dermatitis (AD) and transepidermal water loss (TEWL), both in eczematous lesions and nonlesioned skin.

Major finding: At week 16, a higher proportion of patients receiving dupilumab vs cyclosporine or TCS achieved 50% improvement in the Eczema Area and Severity Index (EASI-50; 81.8% vs 28.6% or 40.0% respectively; P  =  .004). TEWL reduced with both dupilumab (P < .001) and TCS (P  =  .047) in eczematous lesions and with dupilumab in nonlesioned skin (P  =  .006) with dupilumab treatment being associated with achievement of EASI-50 (odds ratio 10.67; P  =  .026) and 50% improvement in TEWL (P  =  .004).

Study details: Findings are from a prospective, observational study including 46 patients with AD who received TCS (n = 10), cyclosporine (n = 14), or dupilumab (n = 22).

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

Source: Montero-Vilchez T et al. Dupilumab improves skin barrier function in adults with atopic dermatitis: A prospective observational study. J Clin Med. 2022;11(12):3341 (Jun 10). Doi:  10.3390/jcm11123341

Key clinical point: Dupilumab was more effective than topical corticosteroids (TCS) and cyclosporine in reducing the severity of atopic dermatitis (AD) and transepidermal water loss (TEWL), both in eczematous lesions and nonlesioned skin.

Major finding: At week 16, a higher proportion of patients receiving dupilumab vs cyclosporine or TCS achieved 50% improvement in the Eczema Area and Severity Index (EASI-50; 81.8% vs 28.6% or 40.0% respectively; P  =  .004). TEWL reduced with both dupilumab (P < .001) and TCS (P  =  .047) in eczematous lesions and with dupilumab in nonlesioned skin (P  =  .006) with dupilumab treatment being associated with achievement of EASI-50 (odds ratio 10.67; P  =  .026) and 50% improvement in TEWL (P  =  .004).

Study details: Findings are from a prospective, observational study including 46 patients with AD who received TCS (n = 10), cyclosporine (n = 14), or dupilumab (n = 22).

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

Source: Montero-Vilchez T et al. Dupilumab improves skin barrier function in adults with atopic dermatitis: A prospective observational study. J Clin Med. 2022;11(12):3341 (Jun 10). Doi:  10.3390/jcm11123341

Key clinical point: Dupilumab was more effective than topical corticosteroids (TCS) and cyclosporine in reducing the severity of atopic dermatitis (AD) and transepidermal water loss (TEWL), both in eczematous lesions and nonlesioned skin.

Major finding: At week 16, a higher proportion of patients receiving dupilumab vs cyclosporine or TCS achieved 50% improvement in the Eczema Area and Severity Index (EASI-50; 81.8% vs 28.6% or 40.0% respectively; P  =  .004). TEWL reduced with both dupilumab (P < .001) and TCS (P  =  .047) in eczematous lesions and with dupilumab in nonlesioned skin (P  =  .006) with dupilumab treatment being associated with achievement of EASI-50 (odds ratio 10.67; P  =  .026) and 50% improvement in TEWL (P  =  .004).

Study details: Findings are from a prospective, observational study including 46 patients with AD who received TCS (n = 10), cyclosporine (n = 14), or dupilumab (n = 22).

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

Source: Montero-Vilchez T et al. Dupilumab improves skin barrier function in adults with atopic dermatitis: A prospective observational study. J Clin Med. 2022;11(12):3341 (Jun 10). Doi:  10.3390/jcm11123341

Key clinical point: Patients with moderate-to-severe atopic dermatitis (AD) who did not achieve Investigator's Global Assessment (IGA) 0/1 response with abrocitinib at week 12, still achieved clinically meaningful improvements in AD severity, itch, and quality of life.

Major finding: At week 12, a higher proportion of IGA nonresponders receiving 200 and 100 mg abrocitinib vs placebo achieved ≥ 75% improvement in the Eczema Area and Severity Index (41.0% and 27.0% vs 9.4%, respectively), ≥4-point improvement in itch (42.8% and 35.2% vs 18.2%, respectively), and ≥4-point improvement in Dermatology Life Quality Index (67.6% and 75.0% vs 49.5%, respectively) scores.

Study details: Findings are from a post hoc analysis of 1 phase 2b and 2 phase 3 (JADE Mono-1 and JADE Mono-2) trials including 548 patients with moderate-to-severe AD who were randomly assigned to receive abrocitinib (200 or 100 mg) or placebo and did not achieve IGA 0/1 response.

Disclosures: This study was funded by Pfizer Inc. Five authors declared being current or former employees and shareholders of Pfizer. The other authors reported ties with various sources, including Pfizer.

Source: Blauvelt A et al. Abrocitinib monotherapy in Investigator’s Global Assessment nonresponders: Improvement in signs and symptoms of atopic dermatitis and quality of life. J Dermatolog Treat. 2022 (Jul 6). Doi: 10.1080/09546634.2022.2059053

Key clinical point: Patients with moderate-to-severe atopic dermatitis (AD) who did not achieve Investigator's Global Assessment (IGA) 0/1 response with abrocitinib at week 12, still achieved clinically meaningful improvements in AD severity, itch, and quality of life.

Major finding: At week 12, a higher proportion of IGA nonresponders receiving 200 and 100 mg abrocitinib vs placebo achieved ≥ 75% improvement in the Eczema Area and Severity Index (41.0% and 27.0% vs 9.4%, respectively), ≥4-point improvement in itch (42.8% and 35.2% vs 18.2%, respectively), and ≥4-point improvement in Dermatology Life Quality Index (67.6% and 75.0% vs 49.5%, respectively) scores.

Study details: Findings are from a post hoc analysis of 1 phase 2b and 2 phase 3 (JADE Mono-1 and JADE Mono-2) trials including 548 patients with moderate-to-severe AD who were randomly assigned to receive abrocitinib (200 or 100 mg) or placebo and did not achieve IGA 0/1 response.

Disclosures: This study was funded by Pfizer Inc. Five authors declared being current or former employees and shareholders of Pfizer. The other authors reported ties with various sources, including Pfizer.

Source: Blauvelt A et al. Abrocitinib monotherapy in Investigator’s Global Assessment nonresponders: Improvement in signs and symptoms of atopic dermatitis and quality of life. J Dermatolog Treat. 2022 (Jul 6). Doi: 10.1080/09546634.2022.2059053

Key clinical point: Patients with moderate-to-severe atopic dermatitis (AD) who did not achieve Investigator's Global Assessment (IGA) 0/1 response with abrocitinib at week 12, still achieved clinically meaningful improvements in AD severity, itch, and quality of life.

Major finding: At week 12, a higher proportion of IGA nonresponders receiving 200 and 100 mg abrocitinib vs placebo achieved ≥ 75% improvement in the Eczema Area and Severity Index (41.0% and 27.0% vs 9.4%, respectively), ≥4-point improvement in itch (42.8% and 35.2% vs 18.2%, respectively), and ≥4-point improvement in Dermatology Life Quality Index (67.6% and 75.0% vs 49.5%, respectively) scores.

Study details: Findings are from a post hoc analysis of 1 phase 2b and 2 phase 3 (JADE Mono-1 and JADE Mono-2) trials including 548 patients with moderate-to-severe AD who were randomly assigned to receive abrocitinib (200 or 100 mg) or placebo and did not achieve IGA 0/1 response.

Disclosures: This study was funded by Pfizer Inc. Five authors declared being current or former employees and shareholders of Pfizer. The other authors reported ties with various sources, including Pfizer.

Source: Blauvelt A et al. Abrocitinib monotherapy in Investigator’s Global Assessment nonresponders: Improvement in signs and symptoms of atopic dermatitis and quality of life. J Dermatolog Treat. 2022 (Jul 6). Doi: 10.1080/09546634.2022.2059053

Key clinical point: Dupilumab led to clinically meaningful improvements in the severity of atopic dermatitis (AD) and was well tolerated in adolescents and children with moderate-to-severe AD.

Major finding: The mean improvement in the Eczema Area and Severity Index (EASI) was 59.6% at week 12-24 and 77.0% at week 36-48 (both P < .001), with all patients achieving ≥75% improvement in EASI score after a year or more of receiving dupilumab. Adverse events like conjunctivitis (5.6%) and joint pain (2.2%) were reported by 13.5% of patients.

Study details: Findings are from a retrospective observational study including 89 children and adolescents aged < 18 years with moderate-to-severe AD who initiated dupilumab treatment.

Disclosures: This study was funded by Pediatric Dermatology Research Alliance. Some authors declared serving as consultants or receiving research funds from several sources.

Source: Pagan AD et al. Dupilumab improves clinical scores in children and adolescents with moderate-to-severe atopic dermatitis: A real-world, single-center study. J Allergy Clin Immunol Pract. 2022 (Jun 23). Doi: 10.1016/j.jaip.2022.06.014

Key clinical point: Dupilumab led to clinically meaningful improvements in the severity of atopic dermatitis (AD) and was well tolerated in adolescents and children with moderate-to-severe AD.

Major finding: The mean improvement in the Eczema Area and Severity Index (EASI) was 59.6% at week 12-24 and 77.0% at week 36-48 (both P < .001), with all patients achieving ≥75% improvement in EASI score after a year or more of receiving dupilumab. Adverse events like conjunctivitis (5.6%) and joint pain (2.2%) were reported by 13.5% of patients.

Study details: Findings are from a retrospective observational study including 89 children and adolescents aged < 18 years with moderate-to-severe AD who initiated dupilumab treatment.

Disclosures: This study was funded by Pediatric Dermatology Research Alliance. Some authors declared serving as consultants or receiving research funds from several sources.

Source: Pagan AD et al. Dupilumab improves clinical scores in children and adolescents with moderate-to-severe atopic dermatitis: A real-world, single-center study. J Allergy Clin Immunol Pract. 2022 (Jun 23). Doi: 10.1016/j.jaip.2022.06.014

Key clinical point: Dupilumab led to clinically meaningful improvements in the severity of atopic dermatitis (AD) and was well tolerated in adolescents and children with moderate-to-severe AD.

Major finding: The mean improvement in the Eczema Area and Severity Index (EASI) was 59.6% at week 12-24 and 77.0% at week 36-48 (both P < .001), with all patients achieving ≥75% improvement in EASI score after a year or more of receiving dupilumab. Adverse events like conjunctivitis (5.6%) and joint pain (2.2%) were reported by 13.5% of patients.

Study details: Findings are from a retrospective observational study including 89 children and adolescents aged < 18 years with moderate-to-severe AD who initiated dupilumab treatment.

Disclosures: This study was funded by Pediatric Dermatology Research Alliance. Some authors declared serving as consultants or receiving research funds from several sources.

Source: Pagan AD et al. Dupilumab improves clinical scores in children and adolescents with moderate-to-severe atopic dermatitis: A real-world, single-center study. J Allergy Clin Immunol Pract. 2022 (Jun 23). Doi: 10.1016/j.jaip.2022.06.014

Key clinical point: Disease burden of atopic dermatitis (AD) is associated with multiple factors, with the strongest association being with disease severity, time spent managing AD symptoms, and comorbid depression.

Major finding: Disease burden was strongly associated with AD severity (moderate: odds ratio [OR] 4.13; 95% CI 2.94-5.79 or severe: OR 13.63; 95% CI 8.65-21.5 vs mild AD), time spent managing AD symptoms (11-20 hours/week: OR 2.67; 95% CI 1.77-4.03 or ≥21 hours/week: OR 5.34; 95% CI 3.22-8.85 vs 0-4 hours/week), and comorbid depression (OR 1.44; 95% CI 1.04-2.00).

Study details: Findings are from a survey study that analyzed the responses of 1065 adults with mostly moderate or severe AD.

Disclosures: This study was partly supported by National Eczema Association. The authors declared serving as fiscal agents or receiving grants, sponsorships, honoraria, or other compensation from several sources, including the National Eczema Association.

Source: Elsawi R et al. The multidimensional burden of atopic dermatitis among adults: Results from a large national survey. JAMA Dermatol. 2022 (Jun 29). Doi: 10.1001/jamadermatol.2022.1906

Key clinical point: Disease burden of atopic dermatitis (AD) is associated with multiple factors, with the strongest association being with disease severity, time spent managing AD symptoms, and comorbid depression.

Major finding: Disease burden was strongly associated with AD severity (moderate: odds ratio [OR] 4.13; 95% CI 2.94-5.79 or severe: OR 13.63; 95% CI 8.65-21.5 vs mild AD), time spent managing AD symptoms (11-20 hours/week: OR 2.67; 95% CI 1.77-4.03 or ≥21 hours/week: OR 5.34; 95% CI 3.22-8.85 vs 0-4 hours/week), and comorbid depression (OR 1.44; 95% CI 1.04-2.00).

Study details: Findings are from a survey study that analyzed the responses of 1065 adults with mostly moderate or severe AD.

Disclosures: This study was partly supported by National Eczema Association. The authors declared serving as fiscal agents or receiving grants, sponsorships, honoraria, or other compensation from several sources, including the National Eczema Association.

Source: Elsawi R et al. The multidimensional burden of atopic dermatitis among adults: Results from a large national survey. JAMA Dermatol. 2022 (Jun 29). Doi: 10.1001/jamadermatol.2022.1906

Key clinical point: Disease burden of atopic dermatitis (AD) is associated with multiple factors, with the strongest association being with disease severity, time spent managing AD symptoms, and comorbid depression.

Major finding: Disease burden was strongly associated with AD severity (moderate: odds ratio [OR] 4.13; 95% CI 2.94-5.79 or severe: OR 13.63; 95% CI 8.65-21.5 vs mild AD), time spent managing AD symptoms (11-20 hours/week: OR 2.67; 95% CI 1.77-4.03 or ≥21 hours/week: OR 5.34; 95% CI 3.22-8.85 vs 0-4 hours/week), and comorbid depression (OR 1.44; 95% CI 1.04-2.00).

Study details: Findings are from a survey study that analyzed the responses of 1065 adults with mostly moderate or severe AD.

Disclosures: This study was partly supported by National Eczema Association. The authors declared serving as fiscal agents or receiving grants, sponsorships, honoraria, or other compensation from several sources, including the National Eczema Association.

Source: Elsawi R et al. The multidimensional burden of atopic dermatitis among adults: Results from a large national survey. JAMA Dermatol. 2022 (Jun 29). Doi: 10.1001/jamadermatol.2022.1906

I was quite sure I had multiple sclerosis when I was a medical student. I first noticed symptoms during my neurology rotation. All the signs were there: Fatigue that was getting worse in the North Carolina heat (Uhthoff sign!). A tingle running down my neck (Lhermitte sign!). Blurry vision late at night while studying pathways in Lange Neurology. “Didn’t cousin Amy have MS?” I asked my Mom. I started researching which medical specialties didn’t require dexterity. My left eyelid began twitching and didn’t stop until I rotated to ob.gyn.

Fortunately, it was not multiple sclerosis I had, but rather nosophobia, also known as Medical Student’s Disease. The combination of intense study of symptoms, spotty knowledge of diagnoses, and grade anxiety makes nosophobia common in med students. Despite its name, it doesn’t afflict only doctors. Patients often come to us convinced they have a disease but without reason. So unshakable is their belief that multiple visits are often required to disabuse them of their self-diagnosis. I sometimes have to remind myself to appear concerned even when a “melanoma” is a freckle so small I can barely see it with a dermatoscope. Or a “genital wart” is a hair follicle that looks exactly like the hundreds on the patient’s scrotum. Tougher though, are the treatment-avoiders: patients whose imagined side effects lead them to stop or refuse treatment.

I recently saw a middle-aged man with erythroderma so severe he looked like a ghillie suit of scale. He had a lifelong history of atopic dermatitis and a 2-year history of avoiding treatments. At some point, he tried all the usual remedies: cyclosporine, methotrexate, azathioprine, light therapy, boxes of topicals. The last treatment had been dupilumab, which he tried for a few weeks. “Why did you stop that one?” I asked. The injections were making him go blind, he explained. “Not blurry? Blind?” I asked. Yes, he could not see at all after each injection. Perhaps he might have dry eyes or keratitis? Sure. But blindness? It seemed an unreasonable concern. Further discussion revealed that intolerance to medication side effects was why he had stopped all his other treatments.

Nocebo, from the Latin “I shall harm,” is the dark counterpart to the placebo. Patients experience imagined, or even real, adverse effects because they believe the treatment is causing them harm. This is true even though that treatment might not be having any unwanted physiologic effect. Statins are a good example. Studies have shown that most patient-reported side effects of statins are in fact nocebo effects rather than a result of pharmacologic causes.

Yet, many patients on statins report muscle pain or other concerns as unbearable. As a consequence, some patients who might have benefited from statins might be missing out on the protective gains. Nocebo effects are exacerbated by a common bias that causes deeper regret when bad outcomes result from an action taken as compared with bad outcomes that occurred from not taking action. It’s frustrating when there’s a standard of care treatment, but our patient can’t get past their fear of harm to try it.

Despite my recommendations, my eczema patient insisted on continuing his nontreatment rather than take any risks with treatments for now. There are ways I might help, but I expect it will require additional visits to build trust. Today, the best I can do is to understand and respect him. At least he doesn’t think he has a genital wart – I’m not sure how I’d treat it if he did.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

I was quite sure I had multiple sclerosis when I was a medical student. I first noticed symptoms during my neurology rotation. All the signs were there: Fatigue that was getting worse in the North Carolina heat (Uhthoff sign!). A tingle running down my neck (Lhermitte sign!). Blurry vision late at night while studying pathways in Lange Neurology. “Didn’t cousin Amy have MS?” I asked my Mom. I started researching which medical specialties didn’t require dexterity. My left eyelid began twitching and didn’t stop until I rotated to ob.gyn.

Fortunately, it was not multiple sclerosis I had, but rather nosophobia, also known as Medical Student’s Disease. The combination of intense study of symptoms, spotty knowledge of diagnoses, and grade anxiety makes nosophobia common in med students. Despite its name, it doesn’t afflict only doctors. Patients often come to us convinced they have a disease but without reason. So unshakable is their belief that multiple visits are often required to disabuse them of their self-diagnosis. I sometimes have to remind myself to appear concerned even when a “melanoma” is a freckle so small I can barely see it with a dermatoscope. Or a “genital wart” is a hair follicle that looks exactly like the hundreds on the patient’s scrotum. Tougher though, are the treatment-avoiders: patients whose imagined side effects lead them to stop or refuse treatment.

I recently saw a middle-aged man with erythroderma so severe he looked like a ghillie suit of scale. He had a lifelong history of atopic dermatitis and a 2-year history of avoiding treatments. At some point, he tried all the usual remedies: cyclosporine, methotrexate, azathioprine, light therapy, boxes of topicals. The last treatment had been dupilumab, which he tried for a few weeks. “Why did you stop that one?” I asked. The injections were making him go blind, he explained. “Not blurry? Blind?” I asked. Yes, he could not see at all after each injection. Perhaps he might have dry eyes or keratitis? Sure. But blindness? It seemed an unreasonable concern. Further discussion revealed that intolerance to medication side effects was why he had stopped all his other treatments.

Nocebo, from the Latin “I shall harm,” is the dark counterpart to the placebo. Patients experience imagined, or even real, adverse effects because they believe the treatment is causing them harm. This is true even though that treatment might not be having any unwanted physiologic effect. Statins are a good example. Studies have shown that most patient-reported side effects of statins are in fact nocebo effects rather than a result of pharmacologic causes.

Yet, many patients on statins report muscle pain or other concerns as unbearable. As a consequence, some patients who might have benefited from statins might be missing out on the protective gains. Nocebo effects are exacerbated by a common bias that causes deeper regret when bad outcomes result from an action taken as compared with bad outcomes that occurred from not taking action. It’s frustrating when there’s a standard of care treatment, but our patient can’t get past their fear of harm to try it.

Despite my recommendations, my eczema patient insisted on continuing his nontreatment rather than take any risks with treatments for now. There are ways I might help, but I expect it will require additional visits to build trust. Today, the best I can do is to understand and respect him. At least he doesn’t think he has a genital wart – I’m not sure how I’d treat it if he did.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

I was quite sure I had multiple sclerosis when I was a medical student. I first noticed symptoms during my neurology rotation. All the signs were there: Fatigue that was getting worse in the North Carolina heat (Uhthoff sign!). A tingle running down my neck (Lhermitte sign!). Blurry vision late at night while studying pathways in Lange Neurology. “Didn’t cousin Amy have MS?” I asked my Mom. I started researching which medical specialties didn’t require dexterity. My left eyelid began twitching and didn’t stop until I rotated to ob.gyn.

Fortunately, it was not multiple sclerosis I had, but rather nosophobia, also known as Medical Student’s Disease. The combination of intense study of symptoms, spotty knowledge of diagnoses, and grade anxiety makes nosophobia common in med students. Despite its name, it doesn’t afflict only doctors. Patients often come to us convinced they have a disease but without reason. So unshakable is their belief that multiple visits are often required to disabuse them of their self-diagnosis. I sometimes have to remind myself to appear concerned even when a “melanoma” is a freckle so small I can barely see it with a dermatoscope. Or a “genital wart” is a hair follicle that looks exactly like the hundreds on the patient’s scrotum. Tougher though, are the treatment-avoiders: patients whose imagined side effects lead them to stop or refuse treatment.

I recently saw a middle-aged man with erythroderma so severe he looked like a ghillie suit of scale. He had a lifelong history of atopic dermatitis and a 2-year history of avoiding treatments. At some point, he tried all the usual remedies: cyclosporine, methotrexate, azathioprine, light therapy, boxes of topicals. The last treatment had been dupilumab, which he tried for a few weeks. “Why did you stop that one?” I asked. The injections were making him go blind, he explained. “Not blurry? Blind?” I asked. Yes, he could not see at all after each injection. Perhaps he might have dry eyes or keratitis? Sure. But blindness? It seemed an unreasonable concern. Further discussion revealed that intolerance to medication side effects was why he had stopped all his other treatments.

Nocebo, from the Latin “I shall harm,” is the dark counterpart to the placebo. Patients experience imagined, or even real, adverse effects because they believe the treatment is causing them harm. This is true even though that treatment might not be having any unwanted physiologic effect. Statins are a good example. Studies have shown that most patient-reported side effects of statins are in fact nocebo effects rather than a result of pharmacologic causes.

Yet, many patients on statins report muscle pain or other concerns as unbearable. As a consequence, some patients who might have benefited from statins might be missing out on the protective gains. Nocebo effects are exacerbated by a common bias that causes deeper regret when bad outcomes result from an action taken as compared with bad outcomes that occurred from not taking action. It’s frustrating when there’s a standard of care treatment, but our patient can’t get past their fear of harm to try it.

Despite my recommendations, my eczema patient insisted on continuing his nontreatment rather than take any risks with treatments for now. There are ways I might help, but I expect it will require additional visits to build trust. Today, the best I can do is to understand and respect him. At least he doesn’t think he has a genital wart – I’m not sure how I’d treat it if he did.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

Patients who take methotrexate for a variety of immune-mediated inflammatory diseases and pause taking the drug following receipt of a COVID-19 vaccine dose did not have a higher risk of disease flare and had higher antireceptor binding domain (anti-RBD) antibody titers and increased immunogenicity when compared with continuing the drug, three recent studies suggest.

In one study, British researchers examined the effects of a 2-week break in methotrexate therapy on anti-RBD titers following receipt of a third COVID-19 vaccine dose. In their paper published in The Lancet: Respiratory Medicine, they reported results from a randomized, open-label, superiority trial that suggested pausing the drug improved immunogenicity, compared with no break.

In two trials presented at the European Alliance of Associations for Rheumatology (EULAR) 2022 Congress, a team from India set out to determine whether holding methotrexate after receiving both doses of a COVID-19 vaccine, or holding it only after the second dose, was safe and effective. They found that pausing methotrexate only following the second dose contributed to a lower flare risk, and that patients had higher anti-RBD titers when holding methotrexate for 2 weeks following each dose.
 

Pausing methotrexate after booster

The 2-week methotrexate break and booster vaccine dose data in the Vaccine Response On Off Methotrexate (VROOM) trial showed that after a month, the geometric mean antispike 1 (S1)-RBD antibody titer was 10,798 U/mL (95% confidence interval [CI], 8,970-12,997) in the group that continued methotrexate and 22,750 U/mL (95% CI, 19,314-26,796) in the group that suspended methotrexate; the geometric mean ratio was 2.19 (P < .0001; mixed-effects model), reported Abhishek Abhishek, MD, PhD, professor of rheumatology at the University of Nottingham in Nottingham, England, and colleagues.

Prior research showed that stopping methotrexate therapy for 2 weeks following the seasonal influenza vaccine contributed to better vaccine immunity among patients with rheumatoid arthritis, but there was no impact of stopping the drug for up to 4 weeks before vaccination on vaccine-related immunity, the researchers noted.

It is crucial in maximizing long-lasting vaccine protection in people who are possibly susceptible through immune suppression at this point in the COVID-19 vaccination regimen, the study team noted.

“Evidence from this study will be useful for policymakers, national immunization advisory committees, and specialist societies formulating recommendations on the use of methotrexate around the time of COVID-19 vaccination. This evidence will help patients and clinicians make informed choices about the risks and benefits of interrupting methotrexate treatment around the time of COVID-19 vaccination, with implications for the potential to extend such approaches to other therapeutics,” they wrote.

In American College of Rheumatology (ACR) guidance for COVID-19 vaccination, the organization advised against using standard synthetic disease-modifying antirheumatic medicines such as methotrexate “for 1-2 weeks (as disease activity allows) after each COVID-19 vaccine dose,” given the at-risk population and public health concerns, Jeffrey A. Sparks, MD, MMSc, assistant professor of medicine and associate physician at Brigham and Women’s Hospital and Harvard Medical School, Boston, and Sara K. Tedeschi, MD, MPH, assistant professor of medicine at Harvard Medical School, noted in an accompanying editorial in The Lancet: Respiratory Medicine.

However, when the ACR developed this statement, there was only one trial involving patients with rheumatoid arthritis who paused methotrexate following seasonal influenza vaccination, the editorialists said.

Expert commentary

This current study is consistent with other studies over the last several months showing that methotrexate harms both humoral and cell-mediated COVID-19 responses, noted Kevin Winthrop, MD, MPH, professor of infectious disease and public health at Oregon Health & Science University, Portland, who was not involved in the study. “And so now the new wave of studies are like this one, where they are holding methotrexate experimentally and seeing if it makes a difference,” he said.

“The one shortcoming of this study – and so far, the studies to date – is that no one has looked at whether the experimental hold has resulted in a change in T-cell responses, which ... we are [now] recognizing [the importance of] more and more in long-term protection, particularly in severe disease. Theoretically, holding [methotrexate] might help enhance T-cell responses, but that hasn’t been shown experimentally.”

Dr. Winthrop pointed out that one might get the same benefit from holding methotrexate for 1 week instead of 2 and that there likely is a reduced risk of flare-up from underlying autoimmune disease.

It is still not certain that this benefit extends to other vaccines, Dr. Winthrop noted. “It is probably true for most vaccines that if you hold methotrexate for 1 or 2 weeks, you might see some short-term benefit in responsiveness, but you don’t know that there is any clinical meaningfulness of this. That’s going to take other long-term studies. You don’t know how long this benefit lasts.”
 

Pausing methotrexate during initial COVID vaccine doses

Patients with either rheumatoid arthritis or psoriatic arthritis had higher anti-RBD antibody titers when methotrexate was stopped after both doses of the AstraZeneca vaccine, or simply after the second dose, than when methotrexate was continued, according to results from two single-center, randomized controlled trials called MIVAC I and II, Anu Sreekanth, MD, of Sree Sudheendra Medical Mission in Kochi, Kerala, India, and colleagues reported at EULAR 2022.

Results from MIVAC I indicated that there was a higher flare rate when methotrexate was stopped after both vaccine doses, but there was no difference in flare rate in MIVAC II when methotrexate was stopped only after the second dose as opposed to stopping it after both doses.

In the MIVAC I trial, 158 unvaccinated patients were randomized 1:1 to a cohort in which methotrexate was held for 2 weeks after both doses and a cohort in which methotrexate was continued despite the vaccine. In MIVAC II, 157 patients continued methotrexate while receiving the first vaccine dose. These patients were subsequently randomized either to continue or to stop methotrexate for 2 weeks following the second dose.

The findings from MIVAC I demonstrated the flare rate was lower in the methotrexate-continue group than in the methotrexate-pause group (8% vs. 25%; P = .005) and that the median anti-RBD titer was significantly higher for the methotrexate-pause group than the methotrexate-continue group (2,484 vs. 1,147; P = .001).

The results from MIVAC II trial indicated that there was no difference in flare rates between the two study groups (7.9% vs. 11.8%; P = .15). Yet, the median anti-RBD titer was significantly higher in the methotrexate-pause cohort than in the methotrexate-continue cohort (2,553 vs. 990; P = .001).

The report suggests there is a flare risk when methotrexate is stopped, Dr. Sreekanth noted. “It appears more logical to hold only after the second dose, as comparable anti-RBD titers are generated” with either approach, Dr. Sreekanth said.

Expert commentary: MIVAC I and II

Inés Colmegna, MD, associate professor at McGill University in Montreal, noted that it was intriguing that the risk of flares in MIVAC II is half of that reported after each of the doses of MIVAC I. “It is also worth emphasizing that despite the reported frequency of flares, the actual disease activity [as measured by the Disease Activity Score in 28 joints] in patients who did or did not withhold methotrexate was similar.

“MIVAC I and II have practical implications as they help to adequately inform patients about the risk and benefit trade of withholding methotrexate post–COVID-19 vaccination,” Dr. Colmegna told this news organization.

“Additional information would help to [further] interpret the findings of these studies, including whether any of the participants were taking any other DMARDs; data on the severity of the flares and functional impact; analysis of factors that predict the risk of flares, such as higher doses of methotrexate; [and change in] disease activity scores pre- and postvaccination,” Dr. Colmegna concluded.

Dr. Abhishek disclosed relationships with Springer, UpTodate, Oxford, Immunotec, AstraZeneca, Inflazome, NGM Biopharmaceuticals, Menarini Pharmaceuticals, and Cadila Pharmaceuticals. Dr. Abhishek is cochair of the ACR/EULAR CPPD Classification Criteria Working Group and the OMERACT CPPD Working Group. Dr. Sparks disclosed relationships with Gilead, Boehringer Ingelheim, Amgen, Bristol-Myers Squibb, and AbbVie, unrelated to this study. Dr. Tedeschi disclosed relationships with ModernaTx and NGM Biopharmaceuticals. Dr. Winthrop disclosed a research grant and serving as a scientific consultant for Pfizer. Dr. Sreekanth  and Dr. Colmegna have disclosed no relevant financial relationships.

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

Patients who take methotrexate for a variety of immune-mediated inflammatory diseases and pause taking the drug following receipt of a COVID-19 vaccine dose did not have a higher risk of disease flare and had higher antireceptor binding domain (anti-RBD) antibody titers and increased immunogenicity when compared with continuing the drug, three recent studies suggest.

In one study, British researchers examined the effects of a 2-week break in methotrexate therapy on anti-RBD titers following receipt of a third COVID-19 vaccine dose. In their paper published in The Lancet: Respiratory Medicine, they reported results from a randomized, open-label, superiority trial that suggested pausing the drug improved immunogenicity, compared with no break.

In two trials presented at the European Alliance of Associations for Rheumatology (EULAR) 2022 Congress, a team from India set out to determine whether holding methotrexate after receiving both doses of a COVID-19 vaccine, or holding it only after the second dose, was safe and effective. They found that pausing methotrexate only following the second dose contributed to a lower flare risk, and that patients had higher anti-RBD titers when holding methotrexate for 2 weeks following each dose.
 

Pausing methotrexate after booster

The 2-week methotrexate break and booster vaccine dose data in the Vaccine Response On Off Methotrexate (VROOM) trial showed that after a month, the geometric mean antispike 1 (S1)-RBD antibody titer was 10,798 U/mL (95% confidence interval [CI], 8,970-12,997) in the group that continued methotrexate and 22,750 U/mL (95% CI, 19,314-26,796) in the group that suspended methotrexate; the geometric mean ratio was 2.19 (P < .0001; mixed-effects model), reported Abhishek Abhishek, MD, PhD, professor of rheumatology at the University of Nottingham in Nottingham, England, and colleagues.

Prior research showed that stopping methotrexate therapy for 2 weeks following the seasonal influenza vaccine contributed to better vaccine immunity among patients with rheumatoid arthritis, but there was no impact of stopping the drug for up to 4 weeks before vaccination on vaccine-related immunity, the researchers noted.

It is crucial in maximizing long-lasting vaccine protection in people who are possibly susceptible through immune suppression at this point in the COVID-19 vaccination regimen, the study team noted.

“Evidence from this study will be useful for policymakers, national immunization advisory committees, and specialist societies formulating recommendations on the use of methotrexate around the time of COVID-19 vaccination. This evidence will help patients and clinicians make informed choices about the risks and benefits of interrupting methotrexate treatment around the time of COVID-19 vaccination, with implications for the potential to extend such approaches to other therapeutics,” they wrote.

In American College of Rheumatology (ACR) guidance for COVID-19 vaccination, the organization advised against using standard synthetic disease-modifying antirheumatic medicines such as methotrexate “for 1-2 weeks (as disease activity allows) after each COVID-19 vaccine dose,” given the at-risk population and public health concerns, Jeffrey A. Sparks, MD, MMSc, assistant professor of medicine and associate physician at Brigham and Women’s Hospital and Harvard Medical School, Boston, and Sara K. Tedeschi, MD, MPH, assistant professor of medicine at Harvard Medical School, noted in an accompanying editorial in The Lancet: Respiratory Medicine.

However, when the ACR developed this statement, there was only one trial involving patients with rheumatoid arthritis who paused methotrexate following seasonal influenza vaccination, the editorialists said.

Expert commentary

This current study is consistent with other studies over the last several months showing that methotrexate harms both humoral and cell-mediated COVID-19 responses, noted Kevin Winthrop, MD, MPH, professor of infectious disease and public health at Oregon Health & Science University, Portland, who was not involved in the study. “And so now the new wave of studies are like this one, where they are holding methotrexate experimentally and seeing if it makes a difference,” he said.

“The one shortcoming of this study – and so far, the studies to date – is that no one has looked at whether the experimental hold has resulted in a change in T-cell responses, which ... we are [now] recognizing [the importance of] more and more in long-term protection, particularly in severe disease. Theoretically, holding [methotrexate] might help enhance T-cell responses, but that hasn’t been shown experimentally.”

Dr. Winthrop pointed out that one might get the same benefit from holding methotrexate for 1 week instead of 2 and that there likely is a reduced risk of flare-up from underlying autoimmune disease.

It is still not certain that this benefit extends to other vaccines, Dr. Winthrop noted. “It is probably true for most vaccines that if you hold methotrexate for 1 or 2 weeks, you might see some short-term benefit in responsiveness, but you don’t know that there is any clinical meaningfulness of this. That’s going to take other long-term studies. You don’t know how long this benefit lasts.”
 

Pausing methotrexate during initial COVID vaccine doses

Patients with either rheumatoid arthritis or psoriatic arthritis had higher anti-RBD antibody titers when methotrexate was stopped after both doses of the AstraZeneca vaccine, or simply after the second dose, than when methotrexate was continued, according to results from two single-center, randomized controlled trials called MIVAC I and II, Anu Sreekanth, MD, of Sree Sudheendra Medical Mission in Kochi, Kerala, India, and colleagues reported at EULAR 2022.

Results from MIVAC I indicated that there was a higher flare rate when methotrexate was stopped after both vaccine doses, but there was no difference in flare rate in MIVAC II when methotrexate was stopped only after the second dose as opposed to stopping it after both doses.

In the MIVAC I trial, 158 unvaccinated patients were randomized 1:1 to a cohort in which methotrexate was held for 2 weeks after both doses and a cohort in which methotrexate was continued despite the vaccine. In MIVAC II, 157 patients continued methotrexate while receiving the first vaccine dose. These patients were subsequently randomized either to continue or to stop methotrexate for 2 weeks following the second dose.

The findings from MIVAC I demonstrated the flare rate was lower in the methotrexate-continue group than in the methotrexate-pause group (8% vs. 25%; P = .005) and that the median anti-RBD titer was significantly higher for the methotrexate-pause group than the methotrexate-continue group (2,484 vs. 1,147; P = .001).

The results from MIVAC II trial indicated that there was no difference in flare rates between the two study groups (7.9% vs. 11.8%; P = .15). Yet, the median anti-RBD titer was significantly higher in the methotrexate-pause cohort than in the methotrexate-continue cohort (2,553 vs. 990; P = .001).

The report suggests there is a flare risk when methotrexate is stopped, Dr. Sreekanth noted. “It appears more logical to hold only after the second dose, as comparable anti-RBD titers are generated” with either approach, Dr. Sreekanth said.

Expert commentary: MIVAC I and II

Inés Colmegna, MD, associate professor at McGill University in Montreal, noted that it was intriguing that the risk of flares in MIVAC II is half of that reported after each of the doses of MIVAC I. “It is also worth emphasizing that despite the reported frequency of flares, the actual disease activity [as measured by the Disease Activity Score in 28 joints] in patients who did or did not withhold methotrexate was similar.

“MIVAC I and II have practical implications as they help to adequately inform patients about the risk and benefit trade of withholding methotrexate post–COVID-19 vaccination,” Dr. Colmegna told this news organization.

“Additional information would help to [further] interpret the findings of these studies, including whether any of the participants were taking any other DMARDs; data on the severity of the flares and functional impact; analysis of factors that predict the risk of flares, such as higher doses of methotrexate; [and change in] disease activity scores pre- and postvaccination,” Dr. Colmegna concluded.

Dr. Abhishek disclosed relationships with Springer, UpTodate, Oxford, Immunotec, AstraZeneca, Inflazome, NGM Biopharmaceuticals, Menarini Pharmaceuticals, and Cadila Pharmaceuticals. Dr. Abhishek is cochair of the ACR/EULAR CPPD Classification Criteria Working Group and the OMERACT CPPD Working Group. Dr. Sparks disclosed relationships with Gilead, Boehringer Ingelheim, Amgen, Bristol-Myers Squibb, and AbbVie, unrelated to this study. Dr. Tedeschi disclosed relationships with ModernaTx and NGM Biopharmaceuticals. Dr. Winthrop disclosed a research grant and serving as a scientific consultant for Pfizer. Dr. Sreekanth  and Dr. Colmegna have disclosed no relevant financial relationships.

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

Patients who take methotrexate for a variety of immune-mediated inflammatory diseases and pause taking the drug following receipt of a COVID-19 vaccine dose did not have a higher risk of disease flare and had higher antireceptor binding domain (anti-RBD) antibody titers and increased immunogenicity when compared with continuing the drug, three recent studies suggest.

In one study, British researchers examined the effects of a 2-week break in methotrexate therapy on anti-RBD titers following receipt of a third COVID-19 vaccine dose. In their paper published in The Lancet: Respiratory Medicine, they reported results from a randomized, open-label, superiority trial that suggested pausing the drug improved immunogenicity, compared with no break.

In two trials presented at the European Alliance of Associations for Rheumatology (EULAR) 2022 Congress, a team from India set out to determine whether holding methotrexate after receiving both doses of a COVID-19 vaccine, or holding it only after the second dose, was safe and effective. They found that pausing methotrexate only following the second dose contributed to a lower flare risk, and that patients had higher anti-RBD titers when holding methotrexate for 2 weeks following each dose.
 

Pausing methotrexate after booster

The 2-week methotrexate break and booster vaccine dose data in the Vaccine Response On Off Methotrexate (VROOM) trial showed that after a month, the geometric mean antispike 1 (S1)-RBD antibody titer was 10,798 U/mL (95% confidence interval [CI], 8,970-12,997) in the group that continued methotrexate and 22,750 U/mL (95% CI, 19,314-26,796) in the group that suspended methotrexate; the geometric mean ratio was 2.19 (P < .0001; mixed-effects model), reported Abhishek Abhishek, MD, PhD, professor of rheumatology at the University of Nottingham in Nottingham, England, and colleagues.

Prior research showed that stopping methotrexate therapy for 2 weeks following the seasonal influenza vaccine contributed to better vaccine immunity among patients with rheumatoid arthritis, but there was no impact of stopping the drug for up to 4 weeks before vaccination on vaccine-related immunity, the researchers noted.

It is crucial in maximizing long-lasting vaccine protection in people who are possibly susceptible through immune suppression at this point in the COVID-19 vaccination regimen, the study team noted.

“Evidence from this study will be useful for policymakers, national immunization advisory committees, and specialist societies formulating recommendations on the use of methotrexate around the time of COVID-19 vaccination. This evidence will help patients and clinicians make informed choices about the risks and benefits of interrupting methotrexate treatment around the time of COVID-19 vaccination, with implications for the potential to extend such approaches to other therapeutics,” they wrote.

In American College of Rheumatology (ACR) guidance for COVID-19 vaccination, the organization advised against using standard synthetic disease-modifying antirheumatic medicines such as methotrexate “for 1-2 weeks (as disease activity allows) after each COVID-19 vaccine dose,” given the at-risk population and public health concerns, Jeffrey A. Sparks, MD, MMSc, assistant professor of medicine and associate physician at Brigham and Women’s Hospital and Harvard Medical School, Boston, and Sara K. Tedeschi, MD, MPH, assistant professor of medicine at Harvard Medical School, noted in an accompanying editorial in The Lancet: Respiratory Medicine.

However, when the ACR developed this statement, there was only one trial involving patients with rheumatoid arthritis who paused methotrexate following seasonal influenza vaccination, the editorialists said.

Expert commentary

This current study is consistent with other studies over the last several months showing that methotrexate harms both humoral and cell-mediated COVID-19 responses, noted Kevin Winthrop, MD, MPH, professor of infectious disease and public health at Oregon Health & Science University, Portland, who was not involved in the study. “And so now the new wave of studies are like this one, where they are holding methotrexate experimentally and seeing if it makes a difference,” he said.

“The one shortcoming of this study – and so far, the studies to date – is that no one has looked at whether the experimental hold has resulted in a change in T-cell responses, which ... we are [now] recognizing [the importance of] more and more in long-term protection, particularly in severe disease. Theoretically, holding [methotrexate] might help enhance T-cell responses, but that hasn’t been shown experimentally.”

Dr. Winthrop pointed out that one might get the same benefit from holding methotrexate for 1 week instead of 2 and that there likely is a reduced risk of flare-up from underlying autoimmune disease.

It is still not certain that this benefit extends to other vaccines, Dr. Winthrop noted. “It is probably true for most vaccines that if you hold methotrexate for 1 or 2 weeks, you might see some short-term benefit in responsiveness, but you don’t know that there is any clinical meaningfulness of this. That’s going to take other long-term studies. You don’t know how long this benefit lasts.”
 

Pausing methotrexate during initial COVID vaccine doses

Patients with either rheumatoid arthritis or psoriatic arthritis had higher anti-RBD antibody titers when methotrexate was stopped after both doses of the AstraZeneca vaccine, or simply after the second dose, than when methotrexate was continued, according to results from two single-center, randomized controlled trials called MIVAC I and II, Anu Sreekanth, MD, of Sree Sudheendra Medical Mission in Kochi, Kerala, India, and colleagues reported at EULAR 2022.

Results from MIVAC I indicated that there was a higher flare rate when methotrexate was stopped after both vaccine doses, but there was no difference in flare rate in MIVAC II when methotrexate was stopped only after the second dose as opposed to stopping it after both doses.

In the MIVAC I trial, 158 unvaccinated patients were randomized 1:1 to a cohort in which methotrexate was held for 2 weeks after both doses and a cohort in which methotrexate was continued despite the vaccine. In MIVAC II, 157 patients continued methotrexate while receiving the first vaccine dose. These patients were subsequently randomized either to continue or to stop methotrexate for 2 weeks following the second dose.

The findings from MIVAC I demonstrated the flare rate was lower in the methotrexate-continue group than in the methotrexate-pause group (8% vs. 25%; P = .005) and that the median anti-RBD titer was significantly higher for the methotrexate-pause group than the methotrexate-continue group (2,484 vs. 1,147; P = .001).

The results from MIVAC II trial indicated that there was no difference in flare rates between the two study groups (7.9% vs. 11.8%; P = .15). Yet, the median anti-RBD titer was significantly higher in the methotrexate-pause cohort than in the methotrexate-continue cohort (2,553 vs. 990; P = .001).

The report suggests there is a flare risk when methotrexate is stopped, Dr. Sreekanth noted. “It appears more logical to hold only after the second dose, as comparable anti-RBD titers are generated” with either approach, Dr. Sreekanth said.

Expert commentary: MIVAC I and II

Inés Colmegna, MD, associate professor at McGill University in Montreal, noted that it was intriguing that the risk of flares in MIVAC II is half of that reported after each of the doses of MIVAC I. “It is also worth emphasizing that despite the reported frequency of flares, the actual disease activity [as measured by the Disease Activity Score in 28 joints] in patients who did or did not withhold methotrexate was similar.

“MIVAC I and II have practical implications as they help to adequately inform patients about the risk and benefit trade of withholding methotrexate post–COVID-19 vaccination,” Dr. Colmegna told this news organization.

“Additional information would help to [further] interpret the findings of these studies, including whether any of the participants were taking any other DMARDs; data on the severity of the flares and functional impact; analysis of factors that predict the risk of flares, such as higher doses of methotrexate; [and change in] disease activity scores pre- and postvaccination,” Dr. Colmegna concluded.

Dr. Abhishek disclosed relationships with Springer, UpTodate, Oxford, Immunotec, AstraZeneca, Inflazome, NGM Biopharmaceuticals, Menarini Pharmaceuticals, and Cadila Pharmaceuticals. Dr. Abhishek is cochair of the ACR/EULAR CPPD Classification Criteria Working Group and the OMERACT CPPD Working Group. Dr. Sparks disclosed relationships with Gilead, Boehringer Ingelheim, Amgen, Bristol-Myers Squibb, and AbbVie, unrelated to this study. Dr. Tedeschi disclosed relationships with ModernaTx and NGM Biopharmaceuticals. Dr. Winthrop disclosed a research grant and serving as a scientific consultant for Pfizer. Dr. Sreekanth  and Dr. Colmegna have disclosed no relevant financial relationships.

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