Psoriatic Arthritis

Key clinical point: Elevated baseline levels of interleukin (IL)-22, IL-17A, and β-defensin (BD)-2 were linked to the achievement of robust skin response with guselkumab in difficult to treat patients with psoriatic arthritis (PsA) who showed inadequate response to tumor necrosis factor inhibitors (TNFi-IR).

Major finding: Levels of IL-22 and BD-2 were elevated in TNFi-IR patients with PsA who did vs did not achieve a ≥90% improvement in Psoriasis Area and Severity Index with guselkumab (P < .05). Levels of IL-17A and BD-2 were similarly elevated in patients who did vs did not respond to Investigator’s Global Assessment 0/1 criteria with guselkumab (all P < .05).

Study details: This post hoc analysis of pooled data from DISCOVER-1, DISCOVER-2, and COSMOS studies included patients with active PsA who were biologic-naive (n = 251) or had TNFi-IR (n = 93) and who received 100 mg guselkumab every 8 weeks.

Disclosures: This study was sponsored by Janssen Research & Development. Ten authors declared being employees of Janssen or subsidiaries or owning stocks or stock options in Johnson & Johnson. Several authors declared other ties with various sources, including Janssen. Other authors had no conflicts of interest.

Source: Siebert S, Coates LC, Schett G, et al. Modulation of IL-23 signaling with guselkumab in biologic-naïve patients versus TNF inhibitor-inadequate responders with active psoriatic arthritis. Arthritis Rheumatol. 2024 (Jan 22). doi: 10.1002/art.42803 Source

Key clinical point: Elevated baseline levels of interleukin (IL)-22, IL-17A, and β-defensin (BD)-2 were linked to the achievement of robust skin response with guselkumab in difficult to treat patients with psoriatic arthritis (PsA) who showed inadequate response to tumor necrosis factor inhibitors (TNFi-IR).

Major finding: Levels of IL-22 and BD-2 were elevated in TNFi-IR patients with PsA who did vs did not achieve a ≥90% improvement in Psoriasis Area and Severity Index with guselkumab (P < .05). Levels of IL-17A and BD-2 were similarly elevated in patients who did vs did not respond to Investigator’s Global Assessment 0/1 criteria with guselkumab (all P < .05).

Study details: This post hoc analysis of pooled data from DISCOVER-1, DISCOVER-2, and COSMOS studies included patients with active PsA who were biologic-naive (n = 251) or had TNFi-IR (n = 93) and who received 100 mg guselkumab every 8 weeks.

Disclosures: This study was sponsored by Janssen Research & Development. Ten authors declared being employees of Janssen or subsidiaries or owning stocks or stock options in Johnson & Johnson. Several authors declared other ties with various sources, including Janssen. Other authors had no conflicts of interest.

Source: Siebert S, Coates LC, Schett G, et al. Modulation of IL-23 signaling with guselkumab in biologic-naïve patients versus TNF inhibitor-inadequate responders with active psoriatic arthritis. Arthritis Rheumatol. 2024 (Jan 22). doi: 10.1002/art.42803 Source

Key clinical point: Elevated baseline levels of interleukin (IL)-22, IL-17A, and β-defensin (BD)-2 were linked to the achievement of robust skin response with guselkumab in difficult to treat patients with psoriatic arthritis (PsA) who showed inadequate response to tumor necrosis factor inhibitors (TNFi-IR).

Major finding: Levels of IL-22 and BD-2 were elevated in TNFi-IR patients with PsA who did vs did not achieve a ≥90% improvement in Psoriasis Area and Severity Index with guselkumab (P < .05). Levels of IL-17A and BD-2 were similarly elevated in patients who did vs did not respond to Investigator’s Global Assessment 0/1 criteria with guselkumab (all P < .05).

Study details: This post hoc analysis of pooled data from DISCOVER-1, DISCOVER-2, and COSMOS studies included patients with active PsA who were biologic-naive (n = 251) or had TNFi-IR (n = 93) and who received 100 mg guselkumab every 8 weeks.

Disclosures: This study was sponsored by Janssen Research & Development. Ten authors declared being employees of Janssen or subsidiaries or owning stocks or stock options in Johnson & Johnson. Several authors declared other ties with various sources, including Janssen. Other authors had no conflicts of interest.

Source: Siebert S, Coates LC, Schett G, et al. Modulation of IL-23 signaling with guselkumab in biologic-naïve patients versus TNF inhibitor-inadequate responders with active psoriatic arthritis. Arthritis Rheumatol. 2024 (Jan 22). doi: 10.1002/art.42803 Source

Key clinical point: Compared with the general population, the prevalence of psychotic disorders was significantly lower in patients with psoriatic arthritis (PsA), but a co-diagnosis of PsA and psychotic disorders was associated with an increased mortality rate, that too at a lower age.

Major finding: The prevalence of psychotic disorders was significantly lower in patients with PsA vs the general population (0.61% vs 0.72%; P = .006). Patients with PsA who did vs did not have psychotic disorders had an increased likelihood of death (9.3% vs 4.9%; P = .005) and significantly lower age at death (64.7 years vs 74.5 years; P < .001).

Study details: This cohort study included 449,392 patients with psoriasis and 47,825 patients with PsA.

Disclosures: The lead author Emilie Brenaut declared receiving a postdoctoral fellowship from the French Society of Dermatology and the Collège des Enseignants en Dermatologie de France as well as personal fees and nonfinancial support from various sources. The other authors reported no conflicts of interest.

Source: Brenaut E, Godin O, Leboyer M, et al. Association between psychotic disorders and psoriasis or psoriatic arthritis: Cohort study of French health insurance database. J Invest Dermatol. 2024 (Jan 19). doi: 10.1016/j.jid.2024.01.005  Source

Key clinical point: Compared with the general population, the prevalence of psychotic disorders was significantly lower in patients with psoriatic arthritis (PsA), but a co-diagnosis of PsA and psychotic disorders was associated with an increased mortality rate, that too at a lower age.

Major finding: The prevalence of psychotic disorders was significantly lower in patients with PsA vs the general population (0.61% vs 0.72%; P = .006). Patients with PsA who did vs did not have psychotic disorders had an increased likelihood of death (9.3% vs 4.9%; P = .005) and significantly lower age at death (64.7 years vs 74.5 years; P < .001).

Study details: This cohort study included 449,392 patients with psoriasis and 47,825 patients with PsA.

Disclosures: The lead author Emilie Brenaut declared receiving a postdoctoral fellowship from the French Society of Dermatology and the Collège des Enseignants en Dermatologie de France as well as personal fees and nonfinancial support from various sources. The other authors reported no conflicts of interest.

Source: Brenaut E, Godin O, Leboyer M, et al. Association between psychotic disorders and psoriasis or psoriatic arthritis: Cohort study of French health insurance database. J Invest Dermatol. 2024 (Jan 19). doi: 10.1016/j.jid.2024.01.005  Source

Key clinical point: Compared with the general population, the prevalence of psychotic disorders was significantly lower in patients with psoriatic arthritis (PsA), but a co-diagnosis of PsA and psychotic disorders was associated with an increased mortality rate, that too at a lower age.

Major finding: The prevalence of psychotic disorders was significantly lower in patients with PsA vs the general population (0.61% vs 0.72%; P = .006). Patients with PsA who did vs did not have psychotic disorders had an increased likelihood of death (9.3% vs 4.9%; P = .005) and significantly lower age at death (64.7 years vs 74.5 years; P < .001).

Study details: This cohort study included 449,392 patients with psoriasis and 47,825 patients with PsA.

Disclosures: The lead author Emilie Brenaut declared receiving a postdoctoral fellowship from the French Society of Dermatology and the Collège des Enseignants en Dermatologie de France as well as personal fees and nonfinancial support from various sources. The other authors reported no conflicts of interest.

Source: Brenaut E, Godin O, Leboyer M, et al. Association between psychotic disorders and psoriasis or psoriatic arthritis: Cohort study of French health insurance database. J Invest Dermatol. 2024 (Jan 19). doi: 10.1016/j.jid.2024.01.005  Source

Key clinical point: Tofacitinib improved disease activity outcomes and clinical manifestations in patients with psoriatic arthritis (PsA) who initiated and continued treatment with tofacitinib.

Major finding: At 6 ± 3 months of follow-up, 25.0% and 7.8% of patients achieved Clinical Disease Activity Index for PsA-defined low disease activity and remission, respectively, and 18.2% of patients achieved minimal disease activity. A substantial proportion of patients also reported the resolution of dactylitis (29.4%) and enthesitis (42.9%).

Study details: Findings are from an observational study including 222 patients with PsA from the CorEvitas PsA/Spondyloarthritis Registry who initiated treatment with tofacitinib, of whom 123 patients had 6 ± 3 months of follow-up.

Disclosures: This study was funded by Pfizer. Four authors declared being employees and stockholders of Pfizer Inc. The other authors declared having ties with various sources, including Pfizer.

Source: Mease PJ, Young P, Fallon L, et al. Effectiveness of tofacitinib in patients initiating therapy for psoriatic arthritis: Results from the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry. Rheumatol Ther. 2024 (Jan 22). doi: 10.1007/s40744-023-00631-4 Source

Key clinical point: Tofacitinib improved disease activity outcomes and clinical manifestations in patients with psoriatic arthritis (PsA) who initiated and continued treatment with tofacitinib.

Major finding: At 6 ± 3 months of follow-up, 25.0% and 7.8% of patients achieved Clinical Disease Activity Index for PsA-defined low disease activity and remission, respectively, and 18.2% of patients achieved minimal disease activity. A substantial proportion of patients also reported the resolution of dactylitis (29.4%) and enthesitis (42.9%).

Study details: Findings are from an observational study including 222 patients with PsA from the CorEvitas PsA/Spondyloarthritis Registry who initiated treatment with tofacitinib, of whom 123 patients had 6 ± 3 months of follow-up.

Disclosures: This study was funded by Pfizer. Four authors declared being employees and stockholders of Pfizer Inc. The other authors declared having ties with various sources, including Pfizer.

Source: Mease PJ, Young P, Fallon L, et al. Effectiveness of tofacitinib in patients initiating therapy for psoriatic arthritis: Results from the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry. Rheumatol Ther. 2024 (Jan 22). doi: 10.1007/s40744-023-00631-4 Source

Key clinical point: Tofacitinib improved disease activity outcomes and clinical manifestations in patients with psoriatic arthritis (PsA) who initiated and continued treatment with tofacitinib.

Major finding: At 6 ± 3 months of follow-up, 25.0% and 7.8% of patients achieved Clinical Disease Activity Index for PsA-defined low disease activity and remission, respectively, and 18.2% of patients achieved minimal disease activity. A substantial proportion of patients also reported the resolution of dactylitis (29.4%) and enthesitis (42.9%).

Study details: Findings are from an observational study including 222 patients with PsA from the CorEvitas PsA/Spondyloarthritis Registry who initiated treatment with tofacitinib, of whom 123 patients had 6 ± 3 months of follow-up.

Disclosures: This study was funded by Pfizer. Four authors declared being employees and stockholders of Pfizer Inc. The other authors declared having ties with various sources, including Pfizer.

Source: Mease PJ, Young P, Fallon L, et al. Effectiveness of tofacitinib in patients initiating therapy for psoriatic arthritis: Results from the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry. Rheumatol Ther. 2024 (Jan 22). doi: 10.1007/s40744-023-00631-4 Source

Key clinical point: In patients with moderate to severe psoriatic arthritis (PsA), risankizumab demonstrated superior efficacy vs placebo in improving disease activity outcomes with a favorable safety profile.

Major finding: A significantly higher number of patients receiving risankizumab vs placebo achieved more than 20% improvement in American College of Rheumatology score at week 24 (risk ratio [RR] 1.760; P < .001) and higher minimal disease activity response (RR 1.827; P < .05). The incidences of serious adverse events and serious treatment-emergent adverse events were similar between the risankizumab and placebo groups (P = .31 and P = .97, respectively).

Study details: This meta-analysis of six randomized controlled trials included 5038 patients with PsA who received either risankizumab or placebo.

Disclosures: This study was supported by grants from the National Natural Science Foundation of China and the Natural Science Foundation of Shanxi Province. The authors declared no conflicts of interest.

Source: Su QY, Zhou HN, Xia GM, et al. Efficacy and safety of risankizumab in patients with psoriatic arthritis: A systematic review and meta-analysis of randomized controlled trials. Rheumatol Ther. 2024 (Feb 1). doi: 10.1007/s40744-024-00638-5 Source

Key clinical point: In patients with moderate to severe psoriatic arthritis (PsA), risankizumab demonstrated superior efficacy vs placebo in improving disease activity outcomes with a favorable safety profile.

Major finding: A significantly higher number of patients receiving risankizumab vs placebo achieved more than 20% improvement in American College of Rheumatology score at week 24 (risk ratio [RR] 1.760; P < .001) and higher minimal disease activity response (RR 1.827; P < .05). The incidences of serious adverse events and serious treatment-emergent adverse events were similar between the risankizumab and placebo groups (P = .31 and P = .97, respectively).

Study details: This meta-analysis of six randomized controlled trials included 5038 patients with PsA who received either risankizumab or placebo.

Disclosures: This study was supported by grants from the National Natural Science Foundation of China and the Natural Science Foundation of Shanxi Province. The authors declared no conflicts of interest.

Source: Su QY, Zhou HN, Xia GM, et al. Efficacy and safety of risankizumab in patients with psoriatic arthritis: A systematic review and meta-analysis of randomized controlled trials. Rheumatol Ther. 2024 (Feb 1). doi: 10.1007/s40744-024-00638-5 Source

Key clinical point: In patients with moderate to severe psoriatic arthritis (PsA), risankizumab demonstrated superior efficacy vs placebo in improving disease activity outcomes with a favorable safety profile.

Major finding: A significantly higher number of patients receiving risankizumab vs placebo achieved more than 20% improvement in American College of Rheumatology score at week 24 (risk ratio [RR] 1.760; P < .001) and higher minimal disease activity response (RR 1.827; P < .05). The incidences of serious adverse events and serious treatment-emergent adverse events were similar between the risankizumab and placebo groups (P = .31 and P = .97, respectively).

Study details: This meta-analysis of six randomized controlled trials included 5038 patients with PsA who received either risankizumab or placebo.

Disclosures: This study was supported by grants from the National Natural Science Foundation of China and the Natural Science Foundation of Shanxi Province. The authors declared no conflicts of interest.

Source: Su QY, Zhou HN, Xia GM, et al. Efficacy and safety of risankizumab in patients with psoriatic arthritis: A systematic review and meta-analysis of randomized controlled trials. Rheumatol Ther. 2024 (Feb 1). doi: 10.1007/s40744-024-00638-5 Source

Key clinical point: Patients with psoriatic arthritis (PsA) showed improvements in enthesitis scores on receiving 15 mg upadacitinib for 24 weeks, with the improvements being maintained for ≤56 weeks.

Major finding: At week 24, a significantly higher proportion of patients achieved a greater improvement in the Leeds Enthesitis Index (LEI) score with 15 mg upadacitinib vs placebo (59.8% vs 38.0%; P < .001), with the improvements being maintained by >65% of patients receiving upadacitinib at week 56. Among patients who achieved resolution (LEI = 0) at week 24, >80% did not have recurrent enthesitis with upadacitinib at week 56.

Study details: This post hoc analysis of the SELECT-PsA 1 and SELECT-PsA 2 trials analyzed the data of patients with PsA who received 15 mg upadacitinib (n = 639) or placebo (n = 635).

Disclosures: This study was funded by AbbVie. Five authors declared being employees of or holding stocks or stock options with AbbVie. Two authors declared receiving consulting fees from or having other ties with various sources, including AbbVie. Fabrizio Cantini declared no conflicts of interest.

Source: Cantini F, Marchesoni A, Novelli L, et al. Effects of upadacitinib on enthesitis in patients with psoriatic arthritis: A post hoc analysis of SELECT-PsA 1 and 2. Rheumatology (Oxford). 2024 (Feb 8). doi: 10.1093/rheumatology/keae057 Source

Key clinical point: Patients with psoriatic arthritis (PsA) showed improvements in enthesitis scores on receiving 15 mg upadacitinib for 24 weeks, with the improvements being maintained for ≤56 weeks.

Major finding: At week 24, a significantly higher proportion of patients achieved a greater improvement in the Leeds Enthesitis Index (LEI) score with 15 mg upadacitinib vs placebo (59.8% vs 38.0%; P < .001), with the improvements being maintained by >65% of patients receiving upadacitinib at week 56. Among patients who achieved resolution (LEI = 0) at week 24, >80% did not have recurrent enthesitis with upadacitinib at week 56.

Study details: This post hoc analysis of the SELECT-PsA 1 and SELECT-PsA 2 trials analyzed the data of patients with PsA who received 15 mg upadacitinib (n = 639) or placebo (n = 635).

Disclosures: This study was funded by AbbVie. Five authors declared being employees of or holding stocks or stock options with AbbVie. Two authors declared receiving consulting fees from or having other ties with various sources, including AbbVie. Fabrizio Cantini declared no conflicts of interest.

Source: Cantini F, Marchesoni A, Novelli L, et al. Effects of upadacitinib on enthesitis in patients with psoriatic arthritis: A post hoc analysis of SELECT-PsA 1 and 2. Rheumatology (Oxford). 2024 (Feb 8). doi: 10.1093/rheumatology/keae057 Source

Key clinical point: Patients with psoriatic arthritis (PsA) showed improvements in enthesitis scores on receiving 15 mg upadacitinib for 24 weeks, with the improvements being maintained for ≤56 weeks.

Major finding: At week 24, a significantly higher proportion of patients achieved a greater improvement in the Leeds Enthesitis Index (LEI) score with 15 mg upadacitinib vs placebo (59.8% vs 38.0%; P < .001), with the improvements being maintained by >65% of patients receiving upadacitinib at week 56. Among patients who achieved resolution (LEI = 0) at week 24, >80% did not have recurrent enthesitis with upadacitinib at week 56.

Study details: This post hoc analysis of the SELECT-PsA 1 and SELECT-PsA 2 trials analyzed the data of patients with PsA who received 15 mg upadacitinib (n = 639) or placebo (n = 635).

Disclosures: This study was funded by AbbVie. Five authors declared being employees of or holding stocks or stock options with AbbVie. Two authors declared receiving consulting fees from or having other ties with various sources, including AbbVie. Fabrizio Cantini declared no conflicts of interest.

Source: Cantini F, Marchesoni A, Novelli L, et al. Effects of upadacitinib on enthesitis in patients with psoriatic arthritis: A post hoc analysis of SELECT-PsA 1 and 2. Rheumatology (Oxford). 2024 (Feb 8). doi: 10.1093/rheumatology/keae057 Source

Key clinical point: Neuropathic pain (NP) led to an increase in obesity-associated factors, such as high serum leptin levels and worsened sleep quality, disease activity outcomes, and fatigue levels in patients with psoriatic arthritis (PsA) who did not have fibromyalgia.

Major finding: Patients with PsA who reported NP vs nociceptive pain had higher serum leptin levels (odds ratio [OR] 1.03; 95% CI 1.007-1.056) and poor sleep quality as assessed by the Insomnia Severity Index score (OR 1.19; 95% CI 1.090-1.297), along with greater fatigue, increased PsA disease activity, poor functioning, and higher disease impact (all P < .001).

Study details: Findings are from a cross-sectional study that included 246 patients with PsA who were not diagnosed with fibromyalgia, depression, anxiety, diabetes, or dyslipidemia.

Disclosures: The study authors declared receiving financial support for the research, authorship, and publication of this study. The authors declared no conflicts of interest.

Source: Toledano E, Queiro R, Gomez-Lechon L, et al. Influence of comorbidities not associated with fibromyalgia on neuropathic pain in patients with psoriatic arthritis: Relationship with clinical parameters. Front Med (Lausanne). 2024;11:1331761 (Jan 24). doi: 10.3389/fmed.2024.1331761 Source

Key clinical point: Neuropathic pain (NP) led to an increase in obesity-associated factors, such as high serum leptin levels and worsened sleep quality, disease activity outcomes, and fatigue levels in patients with psoriatic arthritis (PsA) who did not have fibromyalgia.

Major finding: Patients with PsA who reported NP vs nociceptive pain had higher serum leptin levels (odds ratio [OR] 1.03; 95% CI 1.007-1.056) and poor sleep quality as assessed by the Insomnia Severity Index score (OR 1.19; 95% CI 1.090-1.297), along with greater fatigue, increased PsA disease activity, poor functioning, and higher disease impact (all P < .001).

Study details: Findings are from a cross-sectional study that included 246 patients with PsA who were not diagnosed with fibromyalgia, depression, anxiety, diabetes, or dyslipidemia.

Disclosures: The study authors declared receiving financial support for the research, authorship, and publication of this study. The authors declared no conflicts of interest.

Source: Toledano E, Queiro R, Gomez-Lechon L, et al. Influence of comorbidities not associated with fibromyalgia on neuropathic pain in patients with psoriatic arthritis: Relationship with clinical parameters. Front Med (Lausanne). 2024;11:1331761 (Jan 24). doi: 10.3389/fmed.2024.1331761 Source

Key clinical point: Neuropathic pain (NP) led to an increase in obesity-associated factors, such as high serum leptin levels and worsened sleep quality, disease activity outcomes, and fatigue levels in patients with psoriatic arthritis (PsA) who did not have fibromyalgia.

Major finding: Patients with PsA who reported NP vs nociceptive pain had higher serum leptin levels (odds ratio [OR] 1.03; 95% CI 1.007-1.056) and poor sleep quality as assessed by the Insomnia Severity Index score (OR 1.19; 95% CI 1.090-1.297), along with greater fatigue, increased PsA disease activity, poor functioning, and higher disease impact (all P < .001).

Study details: Findings are from a cross-sectional study that included 246 patients with PsA who were not diagnosed with fibromyalgia, depression, anxiety, diabetes, or dyslipidemia.

Disclosures: The study authors declared receiving financial support for the research, authorship, and publication of this study. The authors declared no conflicts of interest.

Source: Toledano E, Queiro R, Gomez-Lechon L, et al. Influence of comorbidities not associated with fibromyalgia on neuropathic pain in patients with psoriatic arthritis: Relationship with clinical parameters. Front Med (Lausanne). 2024;11:1331761 (Jan 24). doi: 10.3389/fmed.2024.1331761 Source

Key clinical point: Patients with psoriatic arthritis (PsA) had significantly higher levels of aortic vascular inflammation as measured by 18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) scanning than control individuals without PsA who had melanoma.

Major finding: Vascular inflammation of the whole aorta was significantly increased in patients with PsA vs control individuals (mean target-to-background ratio 1.63 vs 1.49; P < .001), with the association remaining significant even after adjusting for gender, age, body mass index, mean arterial pressure, and aortic calcification (P = .002). Patients with PsA vs control individuals also had a higher extent of inflammation in other aortic segments.

Study details: Findings are from cross-sectional study that included 75 patients with active PsA and 40 control individuals without PsA who were diagnosed with melanoma without distant metastases, all of whom underwent FDG PET/CT scans.

Disclosures: This study was funded by Health Holland and Pfizer. Four authors declared serving as consultants or advisors for, receiving research grants from, or having other ties with various sources, including Pfizer.

Source: Kleinrensink NJ, Spierings J, Vonkeman HE, et al. Increased vascular inflammation on PET/CT in psoriatic arthritis patients in comparison with controls. RMD open. 2024;10:e003547 (Jan 30). doi: 10.1136/rmdopen-2023-003547 Source

Key clinical point: Patients with psoriatic arthritis (PsA) had significantly higher levels of aortic vascular inflammation as measured by 18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) scanning than control individuals without PsA who had melanoma.

Major finding: Vascular inflammation of the whole aorta was significantly increased in patients with PsA vs control individuals (mean target-to-background ratio 1.63 vs 1.49; P < .001), with the association remaining significant even after adjusting for gender, age, body mass index, mean arterial pressure, and aortic calcification (P = .002). Patients with PsA vs control individuals also had a higher extent of inflammation in other aortic segments.

Study details: Findings are from cross-sectional study that included 75 patients with active PsA and 40 control individuals without PsA who were diagnosed with melanoma without distant metastases, all of whom underwent FDG PET/CT scans.

Disclosures: This study was funded by Health Holland and Pfizer. Four authors declared serving as consultants or advisors for, receiving research grants from, or having other ties with various sources, including Pfizer.

Source: Kleinrensink NJ, Spierings J, Vonkeman HE, et al. Increased vascular inflammation on PET/CT in psoriatic arthritis patients in comparison with controls. RMD open. 2024;10:e003547 (Jan 30). doi: 10.1136/rmdopen-2023-003547 Source

Key clinical point: Patients with psoriatic arthritis (PsA) had significantly higher levels of aortic vascular inflammation as measured by 18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) scanning than control individuals without PsA who had melanoma.

Major finding: Vascular inflammation of the whole aorta was significantly increased in patients with PsA vs control individuals (mean target-to-background ratio 1.63 vs 1.49; P < .001), with the association remaining significant even after adjusting for gender, age, body mass index, mean arterial pressure, and aortic calcification (P = .002). Patients with PsA vs control individuals also had a higher extent of inflammation in other aortic segments.

Study details: Findings are from cross-sectional study that included 75 patients with active PsA and 40 control individuals without PsA who were diagnosed with melanoma without distant metastases, all of whom underwent FDG PET/CT scans.

Disclosures: This study was funded by Health Holland and Pfizer. Four authors declared serving as consultants or advisors for, receiving research grants from, or having other ties with various sources, including Pfizer.

Source: Kleinrensink NJ, Spierings J, Vonkeman HE, et al. Increased vascular inflammation on PET/CT in psoriatic arthritis patients in comparison with controls. RMD open. 2024;10:e003547 (Jan 30). doi: 10.1136/rmdopen-2023-003547 Source

Pretreatment testing of patients starting systemic immunomodulatory therapies for chronic skin diseases fell short of recommendations, based on an analysis of more than 120,000 individuals in a national commercial insurance claims database.

Because of concerns for the potential reactivation of tuberculosis or hepatitis B or C, or for an increased risk for infections, myelosuppression, and hepatoxicity in the wake of immunomodulator use, some medical societies recommend screening patients for hepatitis B, hepatitis C, and tuberculosis before starting these medications, wrote Maria C. Schneeweiss, MD, of Brigham and Women’s Hospital, Boston, Massachusetts, and colleagues.

“Conducting this study was crucial because of the increasing use of systemic immunomodulatory agents for chronic inflammatory skin diseases and the recognized need for pretreatment testing to prevent complications,” coauthor Denys Shay, a PhD candidate in population health sciences at Harvard University, Cambridge, Massachusetts, said in an interview.

“Despite recommendations from professional societies, there was a lack of clarity on how consistently these guidelines were being followed in the United States. This study aimed to fill that gap in knowledge, providing a comprehensive view of current practices and highlighting areas for improvement,” he said.

In the study, published online in JAMA Dermatology, he and his coauthors identified 122,308 adults in the United States with psoriasis, hidradenitis suppurativa, or atopic dermatitis who started an immunomodulatory agent, including methotrexate (28,684 patients), tumor necrosis factor (TNF)–alpha inhibitors (40,965), ustekinumab (12,841), interleukin (IL)-23 inhibitors (6116), IL-17A inhibitors (9799), dupilumab (7787), and apremilast (16,116). The data were from a commercial insurance claims database from December 31, 2002, to December 31, 2020.

The primary outcome was the proportion of patients who underwent recommended screening lab tests including tuberculosis, hepatitis, liver function, complete blood cell counts (CBCs), and lipid panels within 6 months before treatment initiation and during the first 2 years of treatment. The median age of the study population was 49 years, and 52.1% were male.

A CBC was the most common pretreatment test across treatments, performed in 41%-69% of patients before starting treatment. Tuberculosis screening occurred in 11%-59% of patients within 6 months of initiating treatment, and 3%-26% had updated tests after 1 year. Similarly, 13%-41% of patients underwent hepatitis screening prior to treatment.

The highest levels of pretreatment testing occurred for TNF-alpha inhibitors, ustekinumab, IL-17A inhibitors, and IL-23 inhibitors, with similar patterns, while the lowest levels of testing occurred with apremilast and dupilumab.

Testing prevalence before starting apremilast and after a year of treatment was 15%-45% and 9%-36%, respectively. Testing before initiation and a year into treatment with dupilumab was 11%-41% and 3%-25%, respectively.

The findings were limited by several factors including the descriptive design, which does not allow for evaluation of the testing practices, the researchers said.

However, the results show the extent of patients with chronic inflammatory skin diseases (CISDs) who do not undergo pretreatment testing, and research is needed to create testing practices on the basis of recommendations for each agent and incorporating each patient’s history and clinical profile, they concluded.

“The finding that less than 60% of patients received recommended pretreatment testing was initially somewhat surprising,” Shay said in the interview. “However, the context provided by higher rates of baseline testing within the 6-12 months before treatment initiation and the potential for additional testing not captured by the dataset — such as hospital stays — suggests that the gap may not be as large as this estimate,” he said.

“The key message for clinicians is that there are considerable variations in laboratory testing practices with regard to the initiation of systemic immunomodulatory agents in patients with CISDs,” Shay said. “This represents a divergence from existing testing guidelines.”

“Further research is needed to understand the reasons for the variations in pretreatment testing practices and whether this heterogeneity affects patient outcomes,” he added.

Resist Routine Testing

The study findings represent a call to action in the form of ongoing assessment of the safety, clinical utility, and cost-effectiveness of pretreatment testing, wrote Clinton W. Enos, MD, Ana Ormaza Vera, MD, and Abby S. Van Voorhees, MD, of the Department of Dermatology, Eastern Virginia Medical School, Norfolk, Virginia, in an accompanying editorial.

The data in the current study suggesting less frequent laboratory testing compared with current guidelines could stem from a high comfort level with many of the therapies that have been available and in use for many years, they noted. Clinicians’ lack of knowledge of the laboratory screening and monitoring guidelines also may play a role, they said.

However, the authors cautioned against routine checking of laboratory results “without purpose” and without attention to their clinical utility and cost. “A thorough medical history is essential and can serve as a sensitive indicator of which patients are more at risk for diseases such as TB or hepatitis, thereby allowing for more meaningful laboratory screening use,” they said.

Evidence supporting prescreening labs for the spectrum of systemic agents used in dermatology varies considerably, “some trapped in time and carried forward for decades until finally questioned, others rooted in treatment mechanism and clinical data,” Adam Friedman, MD, professor and chief of dermatology at George Washington University, Washington, DC, said in an interview.

The study elucidated the current state of clinical practice, said Friedman, who was not involved with the study. This includes screening even if the label says it is not necessary and letting screening slide when guidelines say otherwise — even if the guidelines are outdated and insurance requires certain metrics prior to approval, he said.

Looking ahead, “we need better consensus and even better communication/education on said guidance,” Dr. Friedman said. “Clear, concise, evidenced-based, and expert-validated guidance to ensure we are meaningfully using medical resources” is what is needed, he added. “It will certainly take a village, and close collaboration between the industry and practitioners is key to success.”

The study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Shay had no financial conflicts to disclose. Lead author Dr. Schneeweiss disclosed grants from UCB Pharma and AbbVie to Brigham and Women’s Hospital outside the submitted work. Other authors disclosed receiving personal fees from Aetion and grants from UCB Pharma and Takeda outside the submitted work; grants from Amarin, Kowa, Novartis, and Pfizer outside the submitted work; and personal fees from Hims & Hers, AbbVie, Sun Pharmaceuticals, Pfizer, Digital Diagnostics, Lilly, Equillium, ASLAN, Boehringer Ingelheim, ACOM, Olaplex, and Legacy Healthcare during the study. No other disclosures were reported.

Editorial author Dr. Enos disclosed serving as an investigator for Amgen and Castle Biosciences and receiving grants from Arcutis Biotherapeutics outside the submitted work. Dr. Van Voorhees disclosed an honorarium outside the submitted work.

Dr. Friedman had no relevant financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Pretreatment testing of patients starting systemic immunomodulatory therapies for chronic skin diseases fell short of recommendations, based on an analysis of more than 120,000 individuals in a national commercial insurance claims database.

Because of concerns for the potential reactivation of tuberculosis or hepatitis B or C, or for an increased risk for infections, myelosuppression, and hepatoxicity in the wake of immunomodulator use, some medical societies recommend screening patients for hepatitis B, hepatitis C, and tuberculosis before starting these medications, wrote Maria C. Schneeweiss, MD, of Brigham and Women’s Hospital, Boston, Massachusetts, and colleagues.

“Conducting this study was crucial because of the increasing use of systemic immunomodulatory agents for chronic inflammatory skin diseases and the recognized need for pretreatment testing to prevent complications,” coauthor Denys Shay, a PhD candidate in population health sciences at Harvard University, Cambridge, Massachusetts, said in an interview.

“Despite recommendations from professional societies, there was a lack of clarity on how consistently these guidelines were being followed in the United States. This study aimed to fill that gap in knowledge, providing a comprehensive view of current practices and highlighting areas for improvement,” he said.

In the study, published online in JAMA Dermatology, he and his coauthors identified 122,308 adults in the United States with psoriasis, hidradenitis suppurativa, or atopic dermatitis who started an immunomodulatory agent, including methotrexate (28,684 patients), tumor necrosis factor (TNF)–alpha inhibitors (40,965), ustekinumab (12,841), interleukin (IL)-23 inhibitors (6116), IL-17A inhibitors (9799), dupilumab (7787), and apremilast (16,116). The data were from a commercial insurance claims database from December 31, 2002, to December 31, 2020.

The primary outcome was the proportion of patients who underwent recommended screening lab tests including tuberculosis, hepatitis, liver function, complete blood cell counts (CBCs), and lipid panels within 6 months before treatment initiation and during the first 2 years of treatment. The median age of the study population was 49 years, and 52.1% were male.

A CBC was the most common pretreatment test across treatments, performed in 41%-69% of patients before starting treatment. Tuberculosis screening occurred in 11%-59% of patients within 6 months of initiating treatment, and 3%-26% had updated tests after 1 year. Similarly, 13%-41% of patients underwent hepatitis screening prior to treatment.

The highest levels of pretreatment testing occurred for TNF-alpha inhibitors, ustekinumab, IL-17A inhibitors, and IL-23 inhibitors, with similar patterns, while the lowest levels of testing occurred with apremilast and dupilumab.

Testing prevalence before starting apremilast and after a year of treatment was 15%-45% and 9%-36%, respectively. Testing before initiation and a year into treatment with dupilumab was 11%-41% and 3%-25%, respectively.

The findings were limited by several factors including the descriptive design, which does not allow for evaluation of the testing practices, the researchers said.

However, the results show the extent of patients with chronic inflammatory skin diseases (CISDs) who do not undergo pretreatment testing, and research is needed to create testing practices on the basis of recommendations for each agent and incorporating each patient’s history and clinical profile, they concluded.

“The finding that less than 60% of patients received recommended pretreatment testing was initially somewhat surprising,” Shay said in the interview. “However, the context provided by higher rates of baseline testing within the 6-12 months before treatment initiation and the potential for additional testing not captured by the dataset — such as hospital stays — suggests that the gap may not be as large as this estimate,” he said.

“The key message for clinicians is that there are considerable variations in laboratory testing practices with regard to the initiation of systemic immunomodulatory agents in patients with CISDs,” Shay said. “This represents a divergence from existing testing guidelines.”

“Further research is needed to understand the reasons for the variations in pretreatment testing practices and whether this heterogeneity affects patient outcomes,” he added.

Resist Routine Testing

The study findings represent a call to action in the form of ongoing assessment of the safety, clinical utility, and cost-effectiveness of pretreatment testing, wrote Clinton W. Enos, MD, Ana Ormaza Vera, MD, and Abby S. Van Voorhees, MD, of the Department of Dermatology, Eastern Virginia Medical School, Norfolk, Virginia, in an accompanying editorial.

The data in the current study suggesting less frequent laboratory testing compared with current guidelines could stem from a high comfort level with many of the therapies that have been available and in use for many years, they noted. Clinicians’ lack of knowledge of the laboratory screening and monitoring guidelines also may play a role, they said.

However, the authors cautioned against routine checking of laboratory results “without purpose” and without attention to their clinical utility and cost. “A thorough medical history is essential and can serve as a sensitive indicator of which patients are more at risk for diseases such as TB or hepatitis, thereby allowing for more meaningful laboratory screening use,” they said.

Evidence supporting prescreening labs for the spectrum of systemic agents used in dermatology varies considerably, “some trapped in time and carried forward for decades until finally questioned, others rooted in treatment mechanism and clinical data,” Adam Friedman, MD, professor and chief of dermatology at George Washington University, Washington, DC, said in an interview.

The study elucidated the current state of clinical practice, said Friedman, who was not involved with the study. This includes screening even if the label says it is not necessary and letting screening slide when guidelines say otherwise — even if the guidelines are outdated and insurance requires certain metrics prior to approval, he said.

Looking ahead, “we need better consensus and even better communication/education on said guidance,” Dr. Friedman said. “Clear, concise, evidenced-based, and expert-validated guidance to ensure we are meaningfully using medical resources” is what is needed, he added. “It will certainly take a village, and close collaboration between the industry and practitioners is key to success.”

The study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Shay had no financial conflicts to disclose. Lead author Dr. Schneeweiss disclosed grants from UCB Pharma and AbbVie to Brigham and Women’s Hospital outside the submitted work. Other authors disclosed receiving personal fees from Aetion and grants from UCB Pharma and Takeda outside the submitted work; grants from Amarin, Kowa, Novartis, and Pfizer outside the submitted work; and personal fees from Hims & Hers, AbbVie, Sun Pharmaceuticals, Pfizer, Digital Diagnostics, Lilly, Equillium, ASLAN, Boehringer Ingelheim, ACOM, Olaplex, and Legacy Healthcare during the study. No other disclosures were reported.

Editorial author Dr. Enos disclosed serving as an investigator for Amgen and Castle Biosciences and receiving grants from Arcutis Biotherapeutics outside the submitted work. Dr. Van Voorhees disclosed an honorarium outside the submitted work.

Dr. Friedman had no relevant financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Pretreatment testing of patients starting systemic immunomodulatory therapies for chronic skin diseases fell short of recommendations, based on an analysis of more than 120,000 individuals in a national commercial insurance claims database.

Because of concerns for the potential reactivation of tuberculosis or hepatitis B or C, or for an increased risk for infections, myelosuppression, and hepatoxicity in the wake of immunomodulator use, some medical societies recommend screening patients for hepatitis B, hepatitis C, and tuberculosis before starting these medications, wrote Maria C. Schneeweiss, MD, of Brigham and Women’s Hospital, Boston, Massachusetts, and colleagues.

“Conducting this study was crucial because of the increasing use of systemic immunomodulatory agents for chronic inflammatory skin diseases and the recognized need for pretreatment testing to prevent complications,” coauthor Denys Shay, a PhD candidate in population health sciences at Harvard University, Cambridge, Massachusetts, said in an interview.

“Despite recommendations from professional societies, there was a lack of clarity on how consistently these guidelines were being followed in the United States. This study aimed to fill that gap in knowledge, providing a comprehensive view of current practices and highlighting areas for improvement,” he said.

In the study, published online in JAMA Dermatology, he and his coauthors identified 122,308 adults in the United States with psoriasis, hidradenitis suppurativa, or atopic dermatitis who started an immunomodulatory agent, including methotrexate (28,684 patients), tumor necrosis factor (TNF)–alpha inhibitors (40,965), ustekinumab (12,841), interleukin (IL)-23 inhibitors (6116), IL-17A inhibitors (9799), dupilumab (7787), and apremilast (16,116). The data were from a commercial insurance claims database from December 31, 2002, to December 31, 2020.

The primary outcome was the proportion of patients who underwent recommended screening lab tests including tuberculosis, hepatitis, liver function, complete blood cell counts (CBCs), and lipid panels within 6 months before treatment initiation and during the first 2 years of treatment. The median age of the study population was 49 years, and 52.1% were male.

A CBC was the most common pretreatment test across treatments, performed in 41%-69% of patients before starting treatment. Tuberculosis screening occurred in 11%-59% of patients within 6 months of initiating treatment, and 3%-26% had updated tests after 1 year. Similarly, 13%-41% of patients underwent hepatitis screening prior to treatment.

The highest levels of pretreatment testing occurred for TNF-alpha inhibitors, ustekinumab, IL-17A inhibitors, and IL-23 inhibitors, with similar patterns, while the lowest levels of testing occurred with apremilast and dupilumab.

Testing prevalence before starting apremilast and after a year of treatment was 15%-45% and 9%-36%, respectively. Testing before initiation and a year into treatment with dupilumab was 11%-41% and 3%-25%, respectively.

The findings were limited by several factors including the descriptive design, which does not allow for evaluation of the testing practices, the researchers said.

However, the results show the extent of patients with chronic inflammatory skin diseases (CISDs) who do not undergo pretreatment testing, and research is needed to create testing practices on the basis of recommendations for each agent and incorporating each patient’s history and clinical profile, they concluded.

“The finding that less than 60% of patients received recommended pretreatment testing was initially somewhat surprising,” Shay said in the interview. “However, the context provided by higher rates of baseline testing within the 6-12 months before treatment initiation and the potential for additional testing not captured by the dataset — such as hospital stays — suggests that the gap may not be as large as this estimate,” he said.

“The key message for clinicians is that there are considerable variations in laboratory testing practices with regard to the initiation of systemic immunomodulatory agents in patients with CISDs,” Shay said. “This represents a divergence from existing testing guidelines.”

“Further research is needed to understand the reasons for the variations in pretreatment testing practices and whether this heterogeneity affects patient outcomes,” he added.

Resist Routine Testing

The study findings represent a call to action in the form of ongoing assessment of the safety, clinical utility, and cost-effectiveness of pretreatment testing, wrote Clinton W. Enos, MD, Ana Ormaza Vera, MD, and Abby S. Van Voorhees, MD, of the Department of Dermatology, Eastern Virginia Medical School, Norfolk, Virginia, in an accompanying editorial.

The data in the current study suggesting less frequent laboratory testing compared with current guidelines could stem from a high comfort level with many of the therapies that have been available and in use for many years, they noted. Clinicians’ lack of knowledge of the laboratory screening and monitoring guidelines also may play a role, they said.

However, the authors cautioned against routine checking of laboratory results “without purpose” and without attention to their clinical utility and cost. “A thorough medical history is essential and can serve as a sensitive indicator of which patients are more at risk for diseases such as TB or hepatitis, thereby allowing for more meaningful laboratory screening use,” they said.

Evidence supporting prescreening labs for the spectrum of systemic agents used in dermatology varies considerably, “some trapped in time and carried forward for decades until finally questioned, others rooted in treatment mechanism and clinical data,” Adam Friedman, MD, professor and chief of dermatology at George Washington University, Washington, DC, said in an interview.

The study elucidated the current state of clinical practice, said Friedman, who was not involved with the study. This includes screening even if the label says it is not necessary and letting screening slide when guidelines say otherwise — even if the guidelines are outdated and insurance requires certain metrics prior to approval, he said.

Looking ahead, “we need better consensus and even better communication/education on said guidance,” Dr. Friedman said. “Clear, concise, evidenced-based, and expert-validated guidance to ensure we are meaningfully using medical resources” is what is needed, he added. “It will certainly take a village, and close collaboration between the industry and practitioners is key to success.”

The study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Shay had no financial conflicts to disclose. Lead author Dr. Schneeweiss disclosed grants from UCB Pharma and AbbVie to Brigham and Women’s Hospital outside the submitted work. Other authors disclosed receiving personal fees from Aetion and grants from UCB Pharma and Takeda outside the submitted work; grants from Amarin, Kowa, Novartis, and Pfizer outside the submitted work; and personal fees from Hims & Hers, AbbVie, Sun Pharmaceuticals, Pfizer, Digital Diagnostics, Lilly, Equillium, ASLAN, Boehringer Ingelheim, ACOM, Olaplex, and Legacy Healthcare during the study. No other disclosures were reported.

Editorial author Dr. Enos disclosed serving as an investigator for Amgen and Castle Biosciences and receiving grants from Arcutis Biotherapeutics outside the submitted work. Dr. Van Voorhees disclosed an honorarium outside the submitted work.

Dr. Friedman had no relevant financial conflicts to disclose.

A version of this article appeared on Medscape.com.

A novel oral drug for plaque psoriasis that targets the same inflammatory pathway as currently available parenteral therapies showed promise for treating moderate to severe disease in a phase 2 dose-finding trial.

Among 255 patients with plaque psoriasis randomly assigned to receive either placebo or an oral interleukin (IL)–23 receptor antagonist peptide dubbed JNJ-77242113 (Janssen), 79% of those who were assigned to the oral agent at the highest dose of 100 mg twice daily had a reduction in the Psoriasis Area and Severity Index (PASI) score at week 16 of at least 75% (PASI 75) compared with 9% of patients assigned to placebo, reported Robert Bissonnette, MD, from Innovaderm Research in Montreal, Quebec, Canada, and colleagues.

“The level of reduction of psoriasis that was observed with higher doses of JNJ-77242113 at week 16 was similar in magnitude to the responses seen with several of the injectable biologics that are currently approved for psoriasis,” investigators in the FRONTIER 1 trial wrote in The New England Journal of Medicine.

The investigators noted that among patients assigned to the 100-mg dose of the active drug, 60% had a PASI 90 response, which compares favorably with that seen in phase 3 trials of two other orally available therapies for psoriasis, deucravacitinib (Sotyktu) and apremilast (Otezla). They cautioned, however, against drawing any further inferences from these data, because these agents have not been tested head-to-head against JNJ-77242113 in comparison trials.
 

Targets IL-23 and IL-17

The investigational agent is an oral IL-23 receptor antagonist peptide that selectively blocks IL-23 proximal signaling as well as the production of downstream inflammatory cytokines such as IL-17, according to the authors.

“Modulation of the interleukin-23 pathway with the use of monoclonal antibodies has shown efficacy in the treatment of psoriasis and is considered to be associated with a more favorable safety profile than older oral therapies (eg, cyclosporine, acitretin, methotrexate, and dimethyl fumarate),” the investigators wrote.

Currently available biologic agents targeting IL-23 include guselkumab (Tremfya), risankizumab (Skyrizi) and tildrakizumab (Ilumya). These agents require intravenous or subcutaneous administration, whereas JNJ-77242113 is taken orally, giving it a theoretical advantage in terms of patient preference.

The novel drug must be taken twice daily on an empty stomach at least 2 hours before food or drink, and those who take it must wait an additional 30 minutes to eat or drink after taking the drug. (This news organization has learned that in planned phase 3 studies, patients will be instructed to take a double daily dose on awakening and then wait 30 minutes for eating or drinking.)

‘Profoundly Effective’

The results of this study have convinced at least one former skeptic of the efficacy of the novel agent.

“They asked me to do the trial, and I turned it down, because I didn’t believe it would work,” said Mark G. Lebwohl, MD, dean for Clinical Therapeutics at the Icahn School of Medicine at Mount Sinai and professor and chairman emeritus of the Department of Dermatology at Mount Sinai Medicine in New York, NY.

In an interview with this news organization, Dr. Lebwohl said that he was initially dubious that a peptide, a short chain of amino acids directed against a receptor, could be effective because it would likely be digested in the intestinal tract.

“Indeed, more than 99% of it is digested, but the data show that the tiny amount that gets through is profoundly effective,” he said.

“I would never have believed that this was going to work – and it did,” Dr. Lebwohl added.

He has signed on as an investigator in the currently recruiting phase 3 ICONIC-LEAD trial, in which JNJ-77242113 will be tested against placebo in adolescents and adults with moderate to severe plaque psoriasis. 

In an editorial accompanying the study in the NEJM, Joel M. Gelfand, MD, MSCE, vice chair of clinical research and medical director of the Dermatology Clinical Studies Unit at the University of Pennsylvania in Philadelphia, noted that if confirmed in larger studies, the PASI 90 rate at the highest dose “would be similar to the most effective injectable biologics,” with no evidence of increased adverse events at higher doses.

“However, two occurrences of infection (COVID-19 and an infected cyst) and a suicide attempt were reported as serious adverse events; larger trials will be needed to determine whether such events are attributable to chance, psoriasis itself, or inhibition of interleukin-23 signaling,” cautioned Dr. Gelfand, director of the psoriasis and phototherapy treatment center at the University of Pennsylvania.

In an interview, Dr. Lebwohl said that currently available IL-23 signaling inhibitors have an excellent safety profile and that the investigational oral agent also appears to be very safe. “It’s seeing a target whose effects are known, and the effects are all good and not bad,” he said.
 

FRONTIER-1 Details

The investigators enrolled eligible adults aged 18 years or older who had moderate to severe plaque psoriasis as defined by an Investigator’s Global Assessment score ≥ 3, a total body-surface area of psoriasis involvement of at least 10%, and a PASI score ≥ 12 who had received their diagnosis of plaque psoriasis at least 6 months before starting the trial. The participants had to be candidates for phototherapy or systemic psoriasis therapy.

Patients were randomly assigned to the active agent at doses of 25 mg once or twice daily, 50 mg once daily, or 100 mg once or twice daily for 16 weeks. 

There was a clear dose response, with 37% of patients assigned to 25-mg once-daily dose meeting the primary endpoint of a PASI 75 response at week 16 compared with 51% of those assigned to the 25-mg twice-daily dose, 58% assigned to 50-mg once-daily dose, 65% assigned to 100-mg once-daily dose, and 79% assigned to 100-mg twice-daily dose (P for dose response < .001).

As noted previously, 9% of patients in the placebo group had a PASI 75 response at week 16.

After a mean duration of 15.9 weeks, adverse events after the first dose of JNJ-77242113 (all dose groups were pooled for the safety analysis) were reported in 47% of patients on the 25-mg once-daily dose, 49% on 25-mg twice-daily dose, 60% on 50-mg once-daily dose, 44% on 100-mg once-daily dose, and 62% on 100-mg twice-daily dose. Adverse events after the first dose occurred in 51% of patients assigned to placebo.

The incidence of adverse events did not increase significantly with successively higher dose levels.

As noted by Dr. Gelfand in his editorial, there were three serious adverse events, all occurring in patients on the active drug: a case of COVID-19 in one patient and a suicide attempt in one patient, both in the 100-mg once-daily dose group, and an infected cyst in the 50-mg once-daily group. All three events were determined by the principal investigator and the sponsor to be unrelated to JNJ-77242113. 

There were no reports of deaths, major adverse cardiovascular events, or incident cancers during the trial.

The study was supported by Janssen Research and Development. Dr. Bissonnette disclosed institutional research funding and advisory board participation and honoraria with Janssen. Dr. Gelfand disclosed consulting for Janssen Biotech. Dr. Lebwohl disclosed institutional research funding from Janssen but no personal fees.

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

A novel oral drug for plaque psoriasis that targets the same inflammatory pathway as currently available parenteral therapies showed promise for treating moderate to severe disease in a phase 2 dose-finding trial.

Among 255 patients with plaque psoriasis randomly assigned to receive either placebo or an oral interleukin (IL)–23 receptor antagonist peptide dubbed JNJ-77242113 (Janssen), 79% of those who were assigned to the oral agent at the highest dose of 100 mg twice daily had a reduction in the Psoriasis Area and Severity Index (PASI) score at week 16 of at least 75% (PASI 75) compared with 9% of patients assigned to placebo, reported Robert Bissonnette, MD, from Innovaderm Research in Montreal, Quebec, Canada, and colleagues.

“The level of reduction of psoriasis that was observed with higher doses of JNJ-77242113 at week 16 was similar in magnitude to the responses seen with several of the injectable biologics that are currently approved for psoriasis,” investigators in the FRONTIER 1 trial wrote in The New England Journal of Medicine.

The investigators noted that among patients assigned to the 100-mg dose of the active drug, 60% had a PASI 90 response, which compares favorably with that seen in phase 3 trials of two other orally available therapies for psoriasis, deucravacitinib (Sotyktu) and apremilast (Otezla). They cautioned, however, against drawing any further inferences from these data, because these agents have not been tested head-to-head against JNJ-77242113 in comparison trials.
 

Targets IL-23 and IL-17

The investigational agent is an oral IL-23 receptor antagonist peptide that selectively blocks IL-23 proximal signaling as well as the production of downstream inflammatory cytokines such as IL-17, according to the authors.

“Modulation of the interleukin-23 pathway with the use of monoclonal antibodies has shown efficacy in the treatment of psoriasis and is considered to be associated with a more favorable safety profile than older oral therapies (eg, cyclosporine, acitretin, methotrexate, and dimethyl fumarate),” the investigators wrote.

Currently available biologic agents targeting IL-23 include guselkumab (Tremfya), risankizumab (Skyrizi) and tildrakizumab (Ilumya). These agents require intravenous or subcutaneous administration, whereas JNJ-77242113 is taken orally, giving it a theoretical advantage in terms of patient preference.

The novel drug must be taken twice daily on an empty stomach at least 2 hours before food or drink, and those who take it must wait an additional 30 minutes to eat or drink after taking the drug. (This news organization has learned that in planned phase 3 studies, patients will be instructed to take a double daily dose on awakening and then wait 30 minutes for eating or drinking.)

‘Profoundly Effective’

The results of this study have convinced at least one former skeptic of the efficacy of the novel agent.

“They asked me to do the trial, and I turned it down, because I didn’t believe it would work,” said Mark G. Lebwohl, MD, dean for Clinical Therapeutics at the Icahn School of Medicine at Mount Sinai and professor and chairman emeritus of the Department of Dermatology at Mount Sinai Medicine in New York, NY.

In an interview with this news organization, Dr. Lebwohl said that he was initially dubious that a peptide, a short chain of amino acids directed against a receptor, could be effective because it would likely be digested in the intestinal tract.

“Indeed, more than 99% of it is digested, but the data show that the tiny amount that gets through is profoundly effective,” he said.

“I would never have believed that this was going to work – and it did,” Dr. Lebwohl added.

He has signed on as an investigator in the currently recruiting phase 3 ICONIC-LEAD trial, in which JNJ-77242113 will be tested against placebo in adolescents and adults with moderate to severe plaque psoriasis. 

In an editorial accompanying the study in the NEJM, Joel M. Gelfand, MD, MSCE, vice chair of clinical research and medical director of the Dermatology Clinical Studies Unit at the University of Pennsylvania in Philadelphia, noted that if confirmed in larger studies, the PASI 90 rate at the highest dose “would be similar to the most effective injectable biologics,” with no evidence of increased adverse events at higher doses.

“However, two occurrences of infection (COVID-19 and an infected cyst) and a suicide attempt were reported as serious adverse events; larger trials will be needed to determine whether such events are attributable to chance, psoriasis itself, or inhibition of interleukin-23 signaling,” cautioned Dr. Gelfand, director of the psoriasis and phototherapy treatment center at the University of Pennsylvania.

In an interview, Dr. Lebwohl said that currently available IL-23 signaling inhibitors have an excellent safety profile and that the investigational oral agent also appears to be very safe. “It’s seeing a target whose effects are known, and the effects are all good and not bad,” he said.
 

FRONTIER-1 Details

The investigators enrolled eligible adults aged 18 years or older who had moderate to severe plaque psoriasis as defined by an Investigator’s Global Assessment score ≥ 3, a total body-surface area of psoriasis involvement of at least 10%, and a PASI score ≥ 12 who had received their diagnosis of plaque psoriasis at least 6 months before starting the trial. The participants had to be candidates for phototherapy or systemic psoriasis therapy.

Patients were randomly assigned to the active agent at doses of 25 mg once or twice daily, 50 mg once daily, or 100 mg once or twice daily for 16 weeks. 

There was a clear dose response, with 37% of patients assigned to 25-mg once-daily dose meeting the primary endpoint of a PASI 75 response at week 16 compared with 51% of those assigned to the 25-mg twice-daily dose, 58% assigned to 50-mg once-daily dose, 65% assigned to 100-mg once-daily dose, and 79% assigned to 100-mg twice-daily dose (P for dose response < .001).

As noted previously, 9% of patients in the placebo group had a PASI 75 response at week 16.

After a mean duration of 15.9 weeks, adverse events after the first dose of JNJ-77242113 (all dose groups were pooled for the safety analysis) were reported in 47% of patients on the 25-mg once-daily dose, 49% on 25-mg twice-daily dose, 60% on 50-mg once-daily dose, 44% on 100-mg once-daily dose, and 62% on 100-mg twice-daily dose. Adverse events after the first dose occurred in 51% of patients assigned to placebo.

The incidence of adverse events did not increase significantly with successively higher dose levels.

As noted by Dr. Gelfand in his editorial, there were three serious adverse events, all occurring in patients on the active drug: a case of COVID-19 in one patient and a suicide attempt in one patient, both in the 100-mg once-daily dose group, and an infected cyst in the 50-mg once-daily group. All three events were determined by the principal investigator and the sponsor to be unrelated to JNJ-77242113. 

There were no reports of deaths, major adverse cardiovascular events, or incident cancers during the trial.

The study was supported by Janssen Research and Development. Dr. Bissonnette disclosed institutional research funding and advisory board participation and honoraria with Janssen. Dr. Gelfand disclosed consulting for Janssen Biotech. Dr. Lebwohl disclosed institutional research funding from Janssen but no personal fees.

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

A novel oral drug for plaque psoriasis that targets the same inflammatory pathway as currently available parenteral therapies showed promise for treating moderate to severe disease in a phase 2 dose-finding trial.

Among 255 patients with plaque psoriasis randomly assigned to receive either placebo or an oral interleukin (IL)–23 receptor antagonist peptide dubbed JNJ-77242113 (Janssen), 79% of those who were assigned to the oral agent at the highest dose of 100 mg twice daily had a reduction in the Psoriasis Area and Severity Index (PASI) score at week 16 of at least 75% (PASI 75) compared with 9% of patients assigned to placebo, reported Robert Bissonnette, MD, from Innovaderm Research in Montreal, Quebec, Canada, and colleagues.

“The level of reduction of psoriasis that was observed with higher doses of JNJ-77242113 at week 16 was similar in magnitude to the responses seen with several of the injectable biologics that are currently approved for psoriasis,” investigators in the FRONTIER 1 trial wrote in The New England Journal of Medicine.

The investigators noted that among patients assigned to the 100-mg dose of the active drug, 60% had a PASI 90 response, which compares favorably with that seen in phase 3 trials of two other orally available therapies for psoriasis, deucravacitinib (Sotyktu) and apremilast (Otezla). They cautioned, however, against drawing any further inferences from these data, because these agents have not been tested head-to-head against JNJ-77242113 in comparison trials.
 

Targets IL-23 and IL-17

The investigational agent is an oral IL-23 receptor antagonist peptide that selectively blocks IL-23 proximal signaling as well as the production of downstream inflammatory cytokines such as IL-17, according to the authors.

“Modulation of the interleukin-23 pathway with the use of monoclonal antibodies has shown efficacy in the treatment of psoriasis and is considered to be associated with a more favorable safety profile than older oral therapies (eg, cyclosporine, acitretin, methotrexate, and dimethyl fumarate),” the investigators wrote.

Currently available biologic agents targeting IL-23 include guselkumab (Tremfya), risankizumab (Skyrizi) and tildrakizumab (Ilumya). These agents require intravenous or subcutaneous administration, whereas JNJ-77242113 is taken orally, giving it a theoretical advantage in terms of patient preference.

The novel drug must be taken twice daily on an empty stomach at least 2 hours before food or drink, and those who take it must wait an additional 30 minutes to eat or drink after taking the drug. (This news organization has learned that in planned phase 3 studies, patients will be instructed to take a double daily dose on awakening and then wait 30 minutes for eating or drinking.)

‘Profoundly Effective’

The results of this study have convinced at least one former skeptic of the efficacy of the novel agent.

“They asked me to do the trial, and I turned it down, because I didn’t believe it would work,” said Mark G. Lebwohl, MD, dean for Clinical Therapeutics at the Icahn School of Medicine at Mount Sinai and professor and chairman emeritus of the Department of Dermatology at Mount Sinai Medicine in New York, NY.

In an interview with this news organization, Dr. Lebwohl said that he was initially dubious that a peptide, a short chain of amino acids directed against a receptor, could be effective because it would likely be digested in the intestinal tract.

“Indeed, more than 99% of it is digested, but the data show that the tiny amount that gets through is profoundly effective,” he said.

“I would never have believed that this was going to work – and it did,” Dr. Lebwohl added.

He has signed on as an investigator in the currently recruiting phase 3 ICONIC-LEAD trial, in which JNJ-77242113 will be tested against placebo in adolescents and adults with moderate to severe plaque psoriasis. 

In an editorial accompanying the study in the NEJM, Joel M. Gelfand, MD, MSCE, vice chair of clinical research and medical director of the Dermatology Clinical Studies Unit at the University of Pennsylvania in Philadelphia, noted that if confirmed in larger studies, the PASI 90 rate at the highest dose “would be similar to the most effective injectable biologics,” with no evidence of increased adverse events at higher doses.

“However, two occurrences of infection (COVID-19 and an infected cyst) and a suicide attempt were reported as serious adverse events; larger trials will be needed to determine whether such events are attributable to chance, psoriasis itself, or inhibition of interleukin-23 signaling,” cautioned Dr. Gelfand, director of the psoriasis and phototherapy treatment center at the University of Pennsylvania.

In an interview, Dr. Lebwohl said that currently available IL-23 signaling inhibitors have an excellent safety profile and that the investigational oral agent also appears to be very safe. “It’s seeing a target whose effects are known, and the effects are all good and not bad,” he said.
 

FRONTIER-1 Details

The investigators enrolled eligible adults aged 18 years or older who had moderate to severe plaque psoriasis as defined by an Investigator’s Global Assessment score ≥ 3, a total body-surface area of psoriasis involvement of at least 10%, and a PASI score ≥ 12 who had received their diagnosis of plaque psoriasis at least 6 months before starting the trial. The participants had to be candidates for phototherapy or systemic psoriasis therapy.

Patients were randomly assigned to the active agent at doses of 25 mg once or twice daily, 50 mg once daily, or 100 mg once or twice daily for 16 weeks. 

There was a clear dose response, with 37% of patients assigned to 25-mg once-daily dose meeting the primary endpoint of a PASI 75 response at week 16 compared with 51% of those assigned to the 25-mg twice-daily dose, 58% assigned to 50-mg once-daily dose, 65% assigned to 100-mg once-daily dose, and 79% assigned to 100-mg twice-daily dose (P for dose response < .001).

As noted previously, 9% of patients in the placebo group had a PASI 75 response at week 16.

After a mean duration of 15.9 weeks, adverse events after the first dose of JNJ-77242113 (all dose groups were pooled for the safety analysis) were reported in 47% of patients on the 25-mg once-daily dose, 49% on 25-mg twice-daily dose, 60% on 50-mg once-daily dose, 44% on 100-mg once-daily dose, and 62% on 100-mg twice-daily dose. Adverse events after the first dose occurred in 51% of patients assigned to placebo.

The incidence of adverse events did not increase significantly with successively higher dose levels.

As noted by Dr. Gelfand in his editorial, there were three serious adverse events, all occurring in patients on the active drug: a case of COVID-19 in one patient and a suicide attempt in one patient, both in the 100-mg once-daily dose group, and an infected cyst in the 50-mg once-daily group. All three events were determined by the principal investigator and the sponsor to be unrelated to JNJ-77242113. 

There were no reports of deaths, major adverse cardiovascular events, or incident cancers during the trial.

The study was supported by Janssen Research and Development. Dr. Bissonnette disclosed institutional research funding and advisory board participation and honoraria with Janssen. Dr. Gelfand disclosed consulting for Janssen Biotech. Dr. Lebwohl disclosed institutional research funding from Janssen but no personal fees.

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

Comorbidities may play a large role in driving poor pregnancy outcomes in pregnant people with certain immune-mediated inflammatory diseases (IMIDs).

In a new study of 12 individual IMIDs, people with rheumatoid arthritis (RA) or inflammatory bowel disease (IBD) did not have signficantly increased risk for preterm birth (PTB) or low birth weight (LBW), compared with people who did not have an IMID, after adjusting for additional chronic conditions and other confounding factors.

The study was published online on February 1 in eClinicalMedicine.

While many studies have explored the relationships between pregnancy outcomes and IMIDs, “the impact of comorbidities on the relation between IMIDs and pregnancy course is insufficiently examined,” the authors wrote. These previous studies also tended to have a small sample size.
 

Pregnancy Outcome Risks Varied Between IMIDs

To remedy this, researchers used electronic health record data from Providence St Joseph Health — a multistate integrated healthcare system — to identify more than 365,000 pregnant people with live births between January 1, 2013, and December 31, 2022. The cohort included more than 5700 people with at least one of 12 IMIDs: Psoriasis, IBD, RA, spondyloarthritis (SpA), multiple sclerosis, systemic lupus erythematosus (SLE), psoriatic arthritis (PsA), antiphospholipid syndrome (APS), Sjögren syndrome (SjS), vasculitis, sarcoidosis, and systemic sclerosis. The study included only live births with a gestational age of 20 weeks or greater.

Researchers compared maternal-fetal health outcomes between the two groups, controlling for comorbidities including diabetes, cardiovascular disease, chronic kidney disease, obesity, and depression. They also accounted for confounding variables including race, age, smoking status, and socioeconomic status.

In total, 83% of people in the IMID group had no immunomodulatory medication prescriptions during their pregnancy. Of the 17% taking medication, 48%-70% continued taking their medication until delivery. Most patients were White, comprising 62.9% of the non-IMID group and 73.1% of the IMID group.

After adjusting for comorbidities, patients with any of the 12 IMIDs had a 10%-20% higher risk for PTB, LBW, small for gestation age (SGA), and cesarean section than did comparators.

But these risks varied between IMIDs. Patients with RA and IBD did not have an increased risk for PTB or LBW. However, when researchers did not control for comorbidities, pregnancy risks were higher and showed statistical significance in these two groups.

“This suggests that for RA and IBD, comorbidities may be a more important factor for adverse outcomes than the underlying autoimmune disease,” senior author Jennifer Hadlock, MD, an associate professor and director of medical data science at the Institute for Systems Biology in Seattle, Washington, said in a video accompanying a press release.

Overall, the analysis found that women with IMIDs were approximately two to three times more likely to have chronic comorbidities than the control group.

Like previous studies, there was a strong association between SLE and APS and poor pregnancy outcomes, even after controlling for confounding factors. Patients with SpA had a 50% increased risk for PTB, while those with SLE and APS had more than a twofold higher risk. Patients with SLE were 90% more likely than comparators to deliver babies with an SGA condition, while RA patients had a 30% higher risk. SLE was the only condition with an increased risk for LBW (relative risk, 3.5). IBD, RA, PsA, SpA, SLE, APS, and SjS were all associated with a higher likelihood of delivery via cesarean section.

“The findings of this study reveal that the associations between IMIDs and adverse pregnancy outcomes are influenced by the specific type of IMIDs and the presence of comorbidities,” the authors wrote.
 

A Large Study, But How Representative Is It?

Asked to comment on the study, Catherine Sims, MD, a rheumatologist at Duke University Medical Center in Durham, North Carolina, noted that the analysis was much larger than many reproductive rheumatology studies, and “their statistics were phenomenal.”

She agreed that “not all autoimmune diseases are created equal when it comes to pregnancy-associated risks.” However, she added that this study’s patient population may not be totally representative of pregnant people with IMIDs or autoimmune diseases.

“We’re making generalizations about autoimmune diseases based on this demographic of White women who are not taking immunosuppression,” she said.

“We know that race and ethnicity play a huge role in pregnancy outcomes, and Black women have higher maternal and fetal morbidity and mortality, which is likely related to systemic racism and biases in the medical system,” she added. “While the study did control for sociodemographic factors, the population studied is not diverse.”

Only 17% of people with IMID in the cohort were on immunosuppressive medication, which could suggest low disease activity in the study population, Dr. Sims said. If the population generally had well-controlled disease, that could have positioned them for better pregnancy outcomes.

The authors noted that their analysis did not have information on IMID disease activity or severity — one of the limitations of the study.

However, the authors argued that the observed low prescription rate during the study may have increased poor pregnancy outcomes.

“Although this reflects real-world care in the population studied, results from this study may show higher risk than might be achieved with recommended care guidelines,” they wrote.

Ultimately, the authors argued that these findings show how co-occurring health conditions can affect pregnancy outcomes in autoimmune diseases, particularly for RA and IBD.

“There is a need to take comorbidities into consideration for guidelines for patients with inflammatory bowel disease and rheumatoid arthritis and when designing future research to investigate maternal health in patients with IMIDs,” they wrote.

The study was funded by the National Institutes of Health. Dr. Sims declared no relevant financial relationships. Dr. Hadlock has received research funding (paid to the institute) from Pfizer, Novartis, Janssen, Bristol-Myers Squibb, and Gilead.

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

Comorbidities may play a large role in driving poor pregnancy outcomes in pregnant people with certain immune-mediated inflammatory diseases (IMIDs).

In a new study of 12 individual IMIDs, people with rheumatoid arthritis (RA) or inflammatory bowel disease (IBD) did not have signficantly increased risk for preterm birth (PTB) or low birth weight (LBW), compared with people who did not have an IMID, after adjusting for additional chronic conditions and other confounding factors.

The study was published online on February 1 in eClinicalMedicine.

While many studies have explored the relationships between pregnancy outcomes and IMIDs, “the impact of comorbidities on the relation between IMIDs and pregnancy course is insufficiently examined,” the authors wrote. These previous studies also tended to have a small sample size.
 

Pregnancy Outcome Risks Varied Between IMIDs

To remedy this, researchers used electronic health record data from Providence St Joseph Health — a multistate integrated healthcare system — to identify more than 365,000 pregnant people with live births between January 1, 2013, and December 31, 2022. The cohort included more than 5700 people with at least one of 12 IMIDs: Psoriasis, IBD, RA, spondyloarthritis (SpA), multiple sclerosis, systemic lupus erythematosus (SLE), psoriatic arthritis (PsA), antiphospholipid syndrome (APS), Sjögren syndrome (SjS), vasculitis, sarcoidosis, and systemic sclerosis. The study included only live births with a gestational age of 20 weeks or greater.

Researchers compared maternal-fetal health outcomes between the two groups, controlling for comorbidities including diabetes, cardiovascular disease, chronic kidney disease, obesity, and depression. They also accounted for confounding variables including race, age, smoking status, and socioeconomic status.

In total, 83% of people in the IMID group had no immunomodulatory medication prescriptions during their pregnancy. Of the 17% taking medication, 48%-70% continued taking their medication until delivery. Most patients were White, comprising 62.9% of the non-IMID group and 73.1% of the IMID group.

After adjusting for comorbidities, patients with any of the 12 IMIDs had a 10%-20% higher risk for PTB, LBW, small for gestation age (SGA), and cesarean section than did comparators.

But these risks varied between IMIDs. Patients with RA and IBD did not have an increased risk for PTB or LBW. However, when researchers did not control for comorbidities, pregnancy risks were higher and showed statistical significance in these two groups.

“This suggests that for RA and IBD, comorbidities may be a more important factor for adverse outcomes than the underlying autoimmune disease,” senior author Jennifer Hadlock, MD, an associate professor and director of medical data science at the Institute for Systems Biology in Seattle, Washington, said in a video accompanying a press release.

Overall, the analysis found that women with IMIDs were approximately two to three times more likely to have chronic comorbidities than the control group.

Like previous studies, there was a strong association between SLE and APS and poor pregnancy outcomes, even after controlling for confounding factors. Patients with SpA had a 50% increased risk for PTB, while those with SLE and APS had more than a twofold higher risk. Patients with SLE were 90% more likely than comparators to deliver babies with an SGA condition, while RA patients had a 30% higher risk. SLE was the only condition with an increased risk for LBW (relative risk, 3.5). IBD, RA, PsA, SpA, SLE, APS, and SjS were all associated with a higher likelihood of delivery via cesarean section.

“The findings of this study reveal that the associations between IMIDs and adverse pregnancy outcomes are influenced by the specific type of IMIDs and the presence of comorbidities,” the authors wrote.
 

A Large Study, But How Representative Is It?

Asked to comment on the study, Catherine Sims, MD, a rheumatologist at Duke University Medical Center in Durham, North Carolina, noted that the analysis was much larger than many reproductive rheumatology studies, and “their statistics were phenomenal.”

She agreed that “not all autoimmune diseases are created equal when it comes to pregnancy-associated risks.” However, she added that this study’s patient population may not be totally representative of pregnant people with IMIDs or autoimmune diseases.

“We’re making generalizations about autoimmune diseases based on this demographic of White women who are not taking immunosuppression,” she said.

“We know that race and ethnicity play a huge role in pregnancy outcomes, and Black women have higher maternal and fetal morbidity and mortality, which is likely related to systemic racism and biases in the medical system,” she added. “While the study did control for sociodemographic factors, the population studied is not diverse.”

Only 17% of people with IMID in the cohort were on immunosuppressive medication, which could suggest low disease activity in the study population, Dr. Sims said. If the population generally had well-controlled disease, that could have positioned them for better pregnancy outcomes.

The authors noted that their analysis did not have information on IMID disease activity or severity — one of the limitations of the study.

However, the authors argued that the observed low prescription rate during the study may have increased poor pregnancy outcomes.

“Although this reflects real-world care in the population studied, results from this study may show higher risk than might be achieved with recommended care guidelines,” they wrote.

Ultimately, the authors argued that these findings show how co-occurring health conditions can affect pregnancy outcomes in autoimmune diseases, particularly for RA and IBD.

“There is a need to take comorbidities into consideration for guidelines for patients with inflammatory bowel disease and rheumatoid arthritis and when designing future research to investigate maternal health in patients with IMIDs,” they wrote.

The study was funded by the National Institutes of Health. Dr. Sims declared no relevant financial relationships. Dr. Hadlock has received research funding (paid to the institute) from Pfizer, Novartis, Janssen, Bristol-Myers Squibb, and Gilead.

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

Comorbidities may play a large role in driving poor pregnancy outcomes in pregnant people with certain immune-mediated inflammatory diseases (IMIDs).

In a new study of 12 individual IMIDs, people with rheumatoid arthritis (RA) or inflammatory bowel disease (IBD) did not have signficantly increased risk for preterm birth (PTB) or low birth weight (LBW), compared with people who did not have an IMID, after adjusting for additional chronic conditions and other confounding factors.

The study was published online on February 1 in eClinicalMedicine.

While many studies have explored the relationships between pregnancy outcomes and IMIDs, “the impact of comorbidities on the relation between IMIDs and pregnancy course is insufficiently examined,” the authors wrote. These previous studies also tended to have a small sample size.
 

Pregnancy Outcome Risks Varied Between IMIDs

To remedy this, researchers used electronic health record data from Providence St Joseph Health — a multistate integrated healthcare system — to identify more than 365,000 pregnant people with live births between January 1, 2013, and December 31, 2022. The cohort included more than 5700 people with at least one of 12 IMIDs: Psoriasis, IBD, RA, spondyloarthritis (SpA), multiple sclerosis, systemic lupus erythematosus (SLE), psoriatic arthritis (PsA), antiphospholipid syndrome (APS), Sjögren syndrome (SjS), vasculitis, sarcoidosis, and systemic sclerosis. The study included only live births with a gestational age of 20 weeks or greater.

Researchers compared maternal-fetal health outcomes between the two groups, controlling for comorbidities including diabetes, cardiovascular disease, chronic kidney disease, obesity, and depression. They also accounted for confounding variables including race, age, smoking status, and socioeconomic status.

In total, 83% of people in the IMID group had no immunomodulatory medication prescriptions during their pregnancy. Of the 17% taking medication, 48%-70% continued taking their medication until delivery. Most patients were White, comprising 62.9% of the non-IMID group and 73.1% of the IMID group.

After adjusting for comorbidities, patients with any of the 12 IMIDs had a 10%-20% higher risk for PTB, LBW, small for gestation age (SGA), and cesarean section than did comparators.

But these risks varied between IMIDs. Patients with RA and IBD did not have an increased risk for PTB or LBW. However, when researchers did not control for comorbidities, pregnancy risks were higher and showed statistical significance in these two groups.

“This suggests that for RA and IBD, comorbidities may be a more important factor for adverse outcomes than the underlying autoimmune disease,” senior author Jennifer Hadlock, MD, an associate professor and director of medical data science at the Institute for Systems Biology in Seattle, Washington, said in a video accompanying a press release.

Overall, the analysis found that women with IMIDs were approximately two to three times more likely to have chronic comorbidities than the control group.

Like previous studies, there was a strong association between SLE and APS and poor pregnancy outcomes, even after controlling for confounding factors. Patients with SpA had a 50% increased risk for PTB, while those with SLE and APS had more than a twofold higher risk. Patients with SLE were 90% more likely than comparators to deliver babies with an SGA condition, while RA patients had a 30% higher risk. SLE was the only condition with an increased risk for LBW (relative risk, 3.5). IBD, RA, PsA, SpA, SLE, APS, and SjS were all associated with a higher likelihood of delivery via cesarean section.

“The findings of this study reveal that the associations between IMIDs and adverse pregnancy outcomes are influenced by the specific type of IMIDs and the presence of comorbidities,” the authors wrote.
 

A Large Study, But How Representative Is It?

Asked to comment on the study, Catherine Sims, MD, a rheumatologist at Duke University Medical Center in Durham, North Carolina, noted that the analysis was much larger than many reproductive rheumatology studies, and “their statistics were phenomenal.”

She agreed that “not all autoimmune diseases are created equal when it comes to pregnancy-associated risks.” However, she added that this study’s patient population may not be totally representative of pregnant people with IMIDs or autoimmune diseases.

“We’re making generalizations about autoimmune diseases based on this demographic of White women who are not taking immunosuppression,” she said.

“We know that race and ethnicity play a huge role in pregnancy outcomes, and Black women have higher maternal and fetal morbidity and mortality, which is likely related to systemic racism and biases in the medical system,” she added. “While the study did control for sociodemographic factors, the population studied is not diverse.”

Only 17% of people with IMID in the cohort were on immunosuppressive medication, which could suggest low disease activity in the study population, Dr. Sims said. If the population generally had well-controlled disease, that could have positioned them for better pregnancy outcomes.

The authors noted that their analysis did not have information on IMID disease activity or severity — one of the limitations of the study.

However, the authors argued that the observed low prescription rate during the study may have increased poor pregnancy outcomes.

“Although this reflects real-world care in the population studied, results from this study may show higher risk than might be achieved with recommended care guidelines,” they wrote.

Ultimately, the authors argued that these findings show how co-occurring health conditions can affect pregnancy outcomes in autoimmune diseases, particularly for RA and IBD.

“There is a need to take comorbidities into consideration for guidelines for patients with inflammatory bowel disease and rheumatoid arthritis and when designing future research to investigate maternal health in patients with IMIDs,” they wrote.

The study was funded by the National Institutes of Health. Dr. Sims declared no relevant financial relationships. Dr. Hadlock has received research funding (paid to the institute) from Pfizer, Novartis, Janssen, Bristol-Myers Squibb, and Gilead.

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