Psoriatic Arthritis ICYMI

Key clinical point: Patients with psoriatic arthritis (PsA) who had a personal history of psoriasis (pPsA) or a family history of psoriasis and current psoriatic lesions (fPsA/PSO) showed a higher disease activity (DA) and more severe axial joint destruction than those with merely a family history of psoriasis (fPsA).

Major finding: Patients with fPsA/PSO vs. fPsA had higher Disease Activity (DA) Index for PsA (DAPSA; 21.94 vs. 18.41; P = .046) and Bath Ankylosing Spondylitis DA Index (BASDAI; 4.09 vs. 3.74; P = .031) scores and more severe sacroiliitis (odds ratio [OR] 0.508; P = .037). The DAPSA (P = .927) and BASDAI (P = .716) scores were similar in patients with pPsA and fPsA/PSO.

Study details: Findings are from a prospective single-center, cross-sectional study including 296 patients with PsA, of which 145 had pPsA, 96 had fPsA, and 55 had fPsA/PSO.

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

Source: Li S-S et al. Exploring the association between history of psoriasis (PSO) and disease activity in patients with psoriatic arthritis (PsA). Rheumatol Ther. 2022 (May 17). Doi: 10.1007/s40744-022-00455-8

Key clinical point: Patients with psoriatic arthritis (PsA) who had a personal history of psoriasis (pPsA) or a family history of psoriasis and current psoriatic lesions (fPsA/PSO) showed a higher disease activity (DA) and more severe axial joint destruction than those with merely a family history of psoriasis (fPsA).

Major finding: Patients with fPsA/PSO vs. fPsA had higher Disease Activity (DA) Index for PsA (DAPSA; 21.94 vs. 18.41; P = .046) and Bath Ankylosing Spondylitis DA Index (BASDAI; 4.09 vs. 3.74; P = .031) scores and more severe sacroiliitis (odds ratio [OR] 0.508; P = .037). The DAPSA (P = .927) and BASDAI (P = .716) scores were similar in patients with pPsA and fPsA/PSO.

Study details: Findings are from a prospective single-center, cross-sectional study including 296 patients with PsA, of which 145 had pPsA, 96 had fPsA, and 55 had fPsA/PSO.

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

Source: Li S-S et al. Exploring the association between history of psoriasis (PSO) and disease activity in patients with psoriatic arthritis (PsA). Rheumatol Ther. 2022 (May 17). Doi: 10.1007/s40744-022-00455-8

Key clinical point: Patients with psoriatic arthritis (PsA) who had a personal history of psoriasis (pPsA) or a family history of psoriasis and current psoriatic lesions (fPsA/PSO) showed a higher disease activity (DA) and more severe axial joint destruction than those with merely a family history of psoriasis (fPsA).

Major finding: Patients with fPsA/PSO vs. fPsA had higher Disease Activity (DA) Index for PsA (DAPSA; 21.94 vs. 18.41; P = .046) and Bath Ankylosing Spondylitis DA Index (BASDAI; 4.09 vs. 3.74; P = .031) scores and more severe sacroiliitis (odds ratio [OR] 0.508; P = .037). The DAPSA (P = .927) and BASDAI (P = .716) scores were similar in patients with pPsA and fPsA/PSO.

Study details: Findings are from a prospective single-center, cross-sectional study including 296 patients with PsA, of which 145 had pPsA, 96 had fPsA, and 55 had fPsA/PSO.

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

Source: Li S-S et al. Exploring the association between history of psoriasis (PSO) and disease activity in patients with psoriatic arthritis (PsA). Rheumatol Ther. 2022 (May 17). Doi: 10.1007/s40744-022-00455-8

Key clinical point: Difficult-to-treat (D2T) patients with psoriatic arthritis (PsA) have a higher prevalence of fibromyalgia, higher body mass index (BMI), and more comorbidities than non-D2T patients with PsA.

Major finding: The potential D2T vs. non-D2T patients had a significantly higher prevalence of fibromyalgia (22.9% vs. 7.2%; P = .022) and a higher median BMI (27.7 vs. 25.7; P = .032), Functional Comorbidity Index value (1 vs. 0; P = .021), disease activity index value (17.2 vs. 7.1; P < .01), pain level (7 vs. 2.5; P < .01), and Health Assessment Questionnaire Disability Index value (1 vs. 0.25; P < .001). Treatment failure with ≥2 biological or targeted synthetic disease-modifying antirheumatic drugs was observed in 100% vs. 8.5% of D2T vs. non-D2T patients, respectively.

Study details: This retrospective analysis of a longitudinal cohort included 106 patients with PsA, of which 36 patients were considered potential D2T candidates.

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

Source: Perrotta FM et al. Clinical characteristics of potential “difficult-to-treat” patients with psoriatic arthritis: A retrospective analysis of a longitudinal cohort. Rheumatol Ther. 2022 May 25. doi: 10.1007/s40744-022-00461-w.

Key clinical point: Difficult-to-treat (D2T) patients with psoriatic arthritis (PsA) have a higher prevalence of fibromyalgia, higher body mass index (BMI), and more comorbidities than non-D2T patients with PsA.

Major finding: The potential D2T vs. non-D2T patients had a significantly higher prevalence of fibromyalgia (22.9% vs. 7.2%; P = .022) and a higher median BMI (27.7 vs. 25.7; P = .032), Functional Comorbidity Index value (1 vs. 0; P = .021), disease activity index value (17.2 vs. 7.1; P < .01), pain level (7 vs. 2.5; P < .01), and Health Assessment Questionnaire Disability Index value (1 vs. 0.25; P < .001). Treatment failure with ≥2 biological or targeted synthetic disease-modifying antirheumatic drugs was observed in 100% vs. 8.5% of D2T vs. non-D2T patients, respectively.

Study details: This retrospective analysis of a longitudinal cohort included 106 patients with PsA, of which 36 patients were considered potential D2T candidates.

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

Source: Perrotta FM et al. Clinical characteristics of potential “difficult-to-treat” patients with psoriatic arthritis: A retrospective analysis of a longitudinal cohort. Rheumatol Ther. 2022 May 25. doi: 10.1007/s40744-022-00461-w.

Key clinical point: Difficult-to-treat (D2T) patients with psoriatic arthritis (PsA) have a higher prevalence of fibromyalgia, higher body mass index (BMI), and more comorbidities than non-D2T patients with PsA.

Major finding: The potential D2T vs. non-D2T patients had a significantly higher prevalence of fibromyalgia (22.9% vs. 7.2%; P = .022) and a higher median BMI (27.7 vs. 25.7; P = .032), Functional Comorbidity Index value (1 vs. 0; P = .021), disease activity index value (17.2 vs. 7.1; P < .01), pain level (7 vs. 2.5; P < .01), and Health Assessment Questionnaire Disability Index value (1 vs. 0.25; P < .001). Treatment failure with ≥2 biological or targeted synthetic disease-modifying antirheumatic drugs was observed in 100% vs. 8.5% of D2T vs. non-D2T patients, respectively.

Study details: This retrospective analysis of a longitudinal cohort included 106 patients with PsA, of which 36 patients were considered potential D2T candidates.

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

Source: Perrotta FM et al. Clinical characteristics of potential “difficult-to-treat” patients with psoriatic arthritis: A retrospective analysis of a longitudinal cohort. Rheumatol Ther. 2022 May 25. doi: 10.1007/s40744-022-00461-w.

Key clinical point: Golimumab reduced disease activity and improved work productivity, activity, and the quality of life (QoL) in patients with psoriatic arthritis (PsA).

Major finding: At 24 months after golimumab initiation, there was significant decrease in mean Clinical Disease Activity Index (−21.7; P < .0001), along with improvement in total work productivity impairment (P = .0186), presenteeism (P = .0007), activity impairment (P < .0001), and mean QoL (−8.3; P < .0001) scores.

Study details: Findings are from a prospective study including patients with PsA (n = 69), rheumatoid arthritis (n = 95), and axial spondyloarthritis (n = 69) who initiated golimumab; of these 110 patients were followed-up for 24 months.

Disclosures: This study was funded by MSD Austria. The authors declared no conflicts of interest.

Source: Dejaco C et al. A prospective study to evaluate the impact of golimumab therapy on work productivity and activity, and quality of life in patients with rheumatoid arthritis, psoriasis arthritis and axial spondyloarthritis in a real life setting in Austria: The GO-ACTIVE study. Front Med. 2022;9:881943 (Jun 2). Doi: 10.3389/fmed.2022.881943

Key clinical point: Golimumab reduced disease activity and improved work productivity, activity, and the quality of life (QoL) in patients with psoriatic arthritis (PsA).

Major finding: At 24 months after golimumab initiation, there was significant decrease in mean Clinical Disease Activity Index (−21.7; P < .0001), along with improvement in total work productivity impairment (P = .0186), presenteeism (P = .0007), activity impairment (P < .0001), and mean QoL (−8.3; P < .0001) scores.

Study details: Findings are from a prospective study including patients with PsA (n = 69), rheumatoid arthritis (n = 95), and axial spondyloarthritis (n = 69) who initiated golimumab; of these 110 patients were followed-up for 24 months.

Disclosures: This study was funded by MSD Austria. The authors declared no conflicts of interest.

Source: Dejaco C et al. A prospective study to evaluate the impact of golimumab therapy on work productivity and activity, and quality of life in patients with rheumatoid arthritis, psoriasis arthritis and axial spondyloarthritis in a real life setting in Austria: The GO-ACTIVE study. Front Med. 2022;9:881943 (Jun 2). Doi: 10.3389/fmed.2022.881943

Key clinical point: Golimumab reduced disease activity and improved work productivity, activity, and the quality of life (QoL) in patients with psoriatic arthritis (PsA).

Major finding: At 24 months after golimumab initiation, there was significant decrease in mean Clinical Disease Activity Index (−21.7; P < .0001), along with improvement in total work productivity impairment (P = .0186), presenteeism (P = .0007), activity impairment (P < .0001), and mean QoL (−8.3; P < .0001) scores.

Study details: Findings are from a prospective study including patients with PsA (n = 69), rheumatoid arthritis (n = 95), and axial spondyloarthritis (n = 69) who initiated golimumab; of these 110 patients were followed-up for 24 months.

Disclosures: This study was funded by MSD Austria. The authors declared no conflicts of interest.

Source: Dejaco C et al. A prospective study to evaluate the impact of golimumab therapy on work productivity and activity, and quality of life in patients with rheumatoid arthritis, psoriasis arthritis and axial spondyloarthritis in a real life setting in Austria: The GO-ACTIVE study. Front Med. 2022;9:881943 (Jun 2). Doi: 10.3389/fmed.2022.881943

Key clinical point: A higher proportion of patients with psoriatic arthritis (PsA) receiving 15 mg upadacitinib achieved low disease activity (LDA) or remission after the first 6 months of treatment, with the difference being visible even after 1 year of treatment, compared to those who received a placebo.

Major finding: At week 24, a higher proportion of patients receiving 15 mg upadacitinib vs. placebo achieved Disease Activity in PsA LDA (range 35%-48% vs. 4%-16%; P < .05) and remission (range 7%-11% vs. 0%-3%; P < .05), with the responses sustained until 56 weeks.

Study details: This was a post hoc analysis of the SELECT-PsA 1 and SELECT-PsA 2 trials including 1386 adults with PsA and prior inadequate response/intolerance to ≥1 non-biologic or biologic disease-modifying antirheumatic drugs who were randomly assigned to receive upadacitinib (15 or 30 mg), adalimumab, or placebo.

Disclosures: This study was funded by AbbVie, Inc. Four authors declared being current or former employees or stockholders of AbbVie, and other authors reported ties with various sources.

Source: Mease P et al. Disease control with upadacitinib in patients with psoriatic arthritis: A post hoc analysis of the randomized, placebo-controlled SELECT-PsA 1 and 2 phase 3 trials. Rheumatol Ther. 2022 (May 23). Doi: 10.1007/s40744-022-00449-6

Key clinical point: A higher proportion of patients with psoriatic arthritis (PsA) receiving 15 mg upadacitinib achieved low disease activity (LDA) or remission after the first 6 months of treatment, with the difference being visible even after 1 year of treatment, compared to those who received a placebo.

Major finding: At week 24, a higher proportion of patients receiving 15 mg upadacitinib vs. placebo achieved Disease Activity in PsA LDA (range 35%-48% vs. 4%-16%; P < .05) and remission (range 7%-11% vs. 0%-3%; P < .05), with the responses sustained until 56 weeks.

Study details: This was a post hoc analysis of the SELECT-PsA 1 and SELECT-PsA 2 trials including 1386 adults with PsA and prior inadequate response/intolerance to ≥1 non-biologic or biologic disease-modifying antirheumatic drugs who were randomly assigned to receive upadacitinib (15 or 30 mg), adalimumab, or placebo.

Disclosures: This study was funded by AbbVie, Inc. Four authors declared being current or former employees or stockholders of AbbVie, and other authors reported ties with various sources.

Source: Mease P et al. Disease control with upadacitinib in patients with psoriatic arthritis: A post hoc analysis of the randomized, placebo-controlled SELECT-PsA 1 and 2 phase 3 trials. Rheumatol Ther. 2022 (May 23). Doi: 10.1007/s40744-022-00449-6

Key clinical point: A higher proportion of patients with psoriatic arthritis (PsA) receiving 15 mg upadacitinib achieved low disease activity (LDA) or remission after the first 6 months of treatment, with the difference being visible even after 1 year of treatment, compared to those who received a placebo.

Major finding: At week 24, a higher proportion of patients receiving 15 mg upadacitinib vs. placebo achieved Disease Activity in PsA LDA (range 35%-48% vs. 4%-16%; P < .05) and remission (range 7%-11% vs. 0%-3%; P < .05), with the responses sustained until 56 weeks.

Study details: This was a post hoc analysis of the SELECT-PsA 1 and SELECT-PsA 2 trials including 1386 adults with PsA and prior inadequate response/intolerance to ≥1 non-biologic or biologic disease-modifying antirheumatic drugs who were randomly assigned to receive upadacitinib (15 or 30 mg), adalimumab, or placebo.

Disclosures: This study was funded by AbbVie, Inc. Four authors declared being current or former employees or stockholders of AbbVie, and other authors reported ties with various sources.

Source: Mease P et al. Disease control with upadacitinib in patients with psoriatic arthritis: A post hoc analysis of the randomized, placebo-controlled SELECT-PsA 1 and 2 phase 3 trials. Rheumatol Ther. 2022 (May 23). Doi: 10.1007/s40744-022-00449-6

Key clinical point: A substantial proportion of patients with psoriatic arthritis (PsA) achieved resolution of enthesitis within a year of initiating nonsteroidal anti-inflammatory drugs (NSAID) or disease-modifying antirheumatic drugs (DMARD), although the odds were lower in patients with high joint disease activity at baseline.

Major finding: Complete resolution of enthesitis was achieved by 86.12% of patients within a mean period of 8.73 months from therapy initiation, with higher joint activity at baseline being associated with a lower chance of enthesitis resolution (odds ratio 0.97; P = .01).

Study details: Findings are from a retrospective analysis of prospectively collected data of 526 patients with PsA and enthesitis who received no treatment/only NSAID (n = 142), conventional DMARD ± NSAID but without targeted DMARD (n = 196), or targeted DMARD with or without other medications (n = 188).

Disclosures: Dr. Mathew and Dr. Chandran received funding from the National Psoriasis Foundation and University of Toronto, respectively. The authors declared no conflicts of interest.

Source: Mathew AJ et al. Effectiveness of disease modifying anti-rheumatic drugs for enthesitis in a prospective longitudinal psoriatic arthritis cohort. J Rheumatol. 2022 (Jun 1). Doi: 10.3899/jrheum.211231

Key clinical point: A substantial proportion of patients with psoriatic arthritis (PsA) achieved resolution of enthesitis within a year of initiating nonsteroidal anti-inflammatory drugs (NSAID) or disease-modifying antirheumatic drugs (DMARD), although the odds were lower in patients with high joint disease activity at baseline.

Major finding: Complete resolution of enthesitis was achieved by 86.12% of patients within a mean period of 8.73 months from therapy initiation, with higher joint activity at baseline being associated with a lower chance of enthesitis resolution (odds ratio 0.97; P = .01).

Study details: Findings are from a retrospective analysis of prospectively collected data of 526 patients with PsA and enthesitis who received no treatment/only NSAID (n = 142), conventional DMARD ± NSAID but without targeted DMARD (n = 196), or targeted DMARD with or without other medications (n = 188).

Disclosures: Dr. Mathew and Dr. Chandran received funding from the National Psoriasis Foundation and University of Toronto, respectively. The authors declared no conflicts of interest.

Source: Mathew AJ et al. Effectiveness of disease modifying anti-rheumatic drugs for enthesitis in a prospective longitudinal psoriatic arthritis cohort. J Rheumatol. 2022 (Jun 1). Doi: 10.3899/jrheum.211231

Key clinical point: A substantial proportion of patients with psoriatic arthritis (PsA) achieved resolution of enthesitis within a year of initiating nonsteroidal anti-inflammatory drugs (NSAID) or disease-modifying antirheumatic drugs (DMARD), although the odds were lower in patients with high joint disease activity at baseline.

Major finding: Complete resolution of enthesitis was achieved by 86.12% of patients within a mean period of 8.73 months from therapy initiation, with higher joint activity at baseline being associated with a lower chance of enthesitis resolution (odds ratio 0.97; P = .01).

Study details: Findings are from a retrospective analysis of prospectively collected data of 526 patients with PsA and enthesitis who received no treatment/only NSAID (n = 142), conventional DMARD ± NSAID but without targeted DMARD (n = 196), or targeted DMARD with or without other medications (n = 188).

Disclosures: Dr. Mathew and Dr. Chandran received funding from the National Psoriasis Foundation and University of Toronto, respectively. The authors declared no conflicts of interest.

Source: Mathew AJ et al. Effectiveness of disease modifying anti-rheumatic drugs for enthesitis in a prospective longitudinal psoriatic arthritis cohort. J Rheumatol. 2022 (Jun 1). Doi: 10.3899/jrheum.211231

COPENHAGEN – For patients with active psoriatic arthritis for whom tumor necrosis factor (TNF) inhibitors failed to produce an adequate response, use of the dual interleukin-17 (IL-17) inhibitor bimekizumab (Bimzelx) was associated with significant improvement in joint, skin, and health-related quality-of-life parameters, compared with placebo, reported investigators in the phase 3, double-blind, randomized BE COMPLETE trial.

The primary endpoint, which was the percentage of patients who had 50% improvement in American College of Rheumatology response criteria (ACR50) at 16 weeks, was achieved in 43.4% of patients assigned to receive bimekizumab 160 mg every 4 weeks, compared with 6.8% among patients who received placebo, reported Joseph F. Merola, MD, a dermatologist and rheumatologist at Brigham and Women’s Hospital in Boston.

Neil Osterweil/Medscape

“The high-level and exciting take-home [message is] that BE COMPLETE did meet all primary and all ranked secondary endpoints at week 16,” he said at the annual European Congress of Rheumatology.

Also at the congress, Iain McInnes, MD, PhD, of the Institute of Infection, Immunity, and Inflammation at the University of Glasgow, Scotland, presented data from a second phase 3, double-blind, randomized trial called BE OPTIMAL that showed similar benefits for patients with psoriatic arthritis who had not previously received biologic disease-modifying antirheumatic drugs.

Neil Osterweil/Medscape

“This is a new mode of action, inhibiting two cytokines simultaneously,” he said in a late-breaking oral abstract session.

As previously reported by this news organization, use of bimekizumab led to rapid reductions in signs and symptoms of radiographic axial spondyloarthritis in the phase 3 trial called BE MOBILE 2.

Bimekizumab is a monoclonal immunoglobulin G1 antibody that selectively inhibits IL-17A and IL-17F. It is approved in the European Union for treating adults with moderate to severe plaque psoriasis.
 

BE COMPLETE efficacy

Inclusion criteria comprised adult-onset psoriatic arthritis meeting Classification Criteria for Psoriatic Arthritis (CASPAR) for at least 6 months; tender and swollen joint counts of at least 3/68; one or more active psoriatic lesions; and/or a documented history of psoriasis characterized by intolerance to one or two TNF inhibitors or failure of TNF inhibitors. Patients were randomly assigned in a 2:1 ratio to receive either bimekizumab 160 mg every 4 weeks (n = 267) or placebo (n = 133) for 16 weeks.

Some participants are being followed in the extension BE VITAL study, which will evaluate response to treatment and long-term safety. Patients who do enroll in the extension study will be followed for safety for a period of 20 weeks after the last dose.

As noted before, the trial met its primary endpoint of a significant improvement over placebo in ACR50 (hazard ratio, 11.1; P < .001).

In addition, the trial met all ranked secondary endpoints, including the Health Assessment Questionnaire–Disability Index change from baseline, 90% improvement in the Psoriasis Area and Severity Index (PASI90), Short-Form 36-Item Health Survey, and minimal disease activity (P < .001 for all comparisons).

Improvement with bimekizumab was rapid; curves began to separate from placebo by week 4, Dr. Merola said.

BE OPTIMAL efficacy

In this study, which had the same eligibility criteria as BE COMPLETE, patients were randomly assigned in a 2:3:1 ratio to receive 16 weeks of treatment with either placebo, bimekizumab 160 mg every 4 weeks, or adalimumab 40 mg every 2 weeks as a reference treatment.

This trial also met its primary and ranked secondary endpoints, which were similar to those of BE COMPLETE but also included measures of pooled resolution of enthesitis and dactylitis and change from baseline in van der Heijde modified total Sharp score (P < .001 for all comparisons).

In all, 43.9% of patients who received bimekizumab and 45.7% who received adalimumab achieved ACR50 at week 16, compared with 10% of patients who received placebo. The difference between the placebo and bimekizumab groups was significant (P < .001).
 

Safety

More patients who received the two active agents in this trial had treatment-emergent adverse events (TEAEs) in comparison with those in the placebo arm, but the incidence of serious TEAEs was less than 2% in each arm.

The most frequent events were nasopharyngitis, upper respiratory tract infection, headache, diarrhea, and hypertension.

Patients tolerated bimekizumab well, and there were no unexpected safety signals, Dr. McInnes said.
 

Clues to efficacy

In the question-and-answer session following Dr. McInnes’ presentation, Ronald Van Vollenhoven, MD, of the University of Amsterdam, said, “I have a question that is sort of generic in studies of psoriatic arthritis, so it does not only apply to this study, but the skin responses seem to be excellent – PASI90 sounds wonderful – but given that this is the case, is it reasonable to claim that the study is double-blinded in respect to the joints?”

Dr. McInnes replied that while he has considered this conundrum for many years in trials of drugs for psoriatic arthritis, “it doesn’t seem to be a major determinant of the outcome.”

The studies were supported by UCB Pharma. Dr. Merola and Dr. McInnes have consulted for UCB and other pharmaceutical companies that market drugs for psoriatic arthritis and psoriasis. Dr. Van Vollenhoven has received research support, has consulted for, and has spoken on behalf of UCB and other pharmaceutical companies.

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

COPENHAGEN – For patients with active psoriatic arthritis for whom tumor necrosis factor (TNF) inhibitors failed to produce an adequate response, use of the dual interleukin-17 (IL-17) inhibitor bimekizumab (Bimzelx) was associated with significant improvement in joint, skin, and health-related quality-of-life parameters, compared with placebo, reported investigators in the phase 3, double-blind, randomized BE COMPLETE trial.

The primary endpoint, which was the percentage of patients who had 50% improvement in American College of Rheumatology response criteria (ACR50) at 16 weeks, was achieved in 43.4% of patients assigned to receive bimekizumab 160 mg every 4 weeks, compared with 6.8% among patients who received placebo, reported Joseph F. Merola, MD, a dermatologist and rheumatologist at Brigham and Women’s Hospital in Boston.

Neil Osterweil/Medscape

“The high-level and exciting take-home [message is] that BE COMPLETE did meet all primary and all ranked secondary endpoints at week 16,” he said at the annual European Congress of Rheumatology.

Also at the congress, Iain McInnes, MD, PhD, of the Institute of Infection, Immunity, and Inflammation at the University of Glasgow, Scotland, presented data from a second phase 3, double-blind, randomized trial called BE OPTIMAL that showed similar benefits for patients with psoriatic arthritis who had not previously received biologic disease-modifying antirheumatic drugs.

Neil Osterweil/Medscape

“This is a new mode of action, inhibiting two cytokines simultaneously,” he said in a late-breaking oral abstract session.

As previously reported by this news organization, use of bimekizumab led to rapid reductions in signs and symptoms of radiographic axial spondyloarthritis in the phase 3 trial called BE MOBILE 2.

Bimekizumab is a monoclonal immunoglobulin G1 antibody that selectively inhibits IL-17A and IL-17F. It is approved in the European Union for treating adults with moderate to severe plaque psoriasis.
 

BE COMPLETE efficacy

Inclusion criteria comprised adult-onset psoriatic arthritis meeting Classification Criteria for Psoriatic Arthritis (CASPAR) for at least 6 months; tender and swollen joint counts of at least 3/68; one or more active psoriatic lesions; and/or a documented history of psoriasis characterized by intolerance to one or two TNF inhibitors or failure of TNF inhibitors. Patients were randomly assigned in a 2:1 ratio to receive either bimekizumab 160 mg every 4 weeks (n = 267) or placebo (n = 133) for 16 weeks.

Some participants are being followed in the extension BE VITAL study, which will evaluate response to treatment and long-term safety. Patients who do enroll in the extension study will be followed for safety for a period of 20 weeks after the last dose.

As noted before, the trial met its primary endpoint of a significant improvement over placebo in ACR50 (hazard ratio, 11.1; P < .001).

In addition, the trial met all ranked secondary endpoints, including the Health Assessment Questionnaire–Disability Index change from baseline, 90% improvement in the Psoriasis Area and Severity Index (PASI90), Short-Form 36-Item Health Survey, and minimal disease activity (P < .001 for all comparisons).

Improvement with bimekizumab was rapid; curves began to separate from placebo by week 4, Dr. Merola said.

BE OPTIMAL efficacy

In this study, which had the same eligibility criteria as BE COMPLETE, patients were randomly assigned in a 2:3:1 ratio to receive 16 weeks of treatment with either placebo, bimekizumab 160 mg every 4 weeks, or adalimumab 40 mg every 2 weeks as a reference treatment.

This trial also met its primary and ranked secondary endpoints, which were similar to those of BE COMPLETE but also included measures of pooled resolution of enthesitis and dactylitis and change from baseline in van der Heijde modified total Sharp score (P < .001 for all comparisons).

In all, 43.9% of patients who received bimekizumab and 45.7% who received adalimumab achieved ACR50 at week 16, compared with 10% of patients who received placebo. The difference between the placebo and bimekizumab groups was significant (P < .001).
 

Safety

More patients who received the two active agents in this trial had treatment-emergent adverse events (TEAEs) in comparison with those in the placebo arm, but the incidence of serious TEAEs was less than 2% in each arm.

The most frequent events were nasopharyngitis, upper respiratory tract infection, headache, diarrhea, and hypertension.

Patients tolerated bimekizumab well, and there were no unexpected safety signals, Dr. McInnes said.
 

Clues to efficacy

In the question-and-answer session following Dr. McInnes’ presentation, Ronald Van Vollenhoven, MD, of the University of Amsterdam, said, “I have a question that is sort of generic in studies of psoriatic arthritis, so it does not only apply to this study, but the skin responses seem to be excellent – PASI90 sounds wonderful – but given that this is the case, is it reasonable to claim that the study is double-blinded in respect to the joints?”

Dr. McInnes replied that while he has considered this conundrum for many years in trials of drugs for psoriatic arthritis, “it doesn’t seem to be a major determinant of the outcome.”

The studies were supported by UCB Pharma. Dr. Merola and Dr. McInnes have consulted for UCB and other pharmaceutical companies that market drugs for psoriatic arthritis and psoriasis. Dr. Van Vollenhoven has received research support, has consulted for, and has spoken on behalf of UCB and other pharmaceutical companies.

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

COPENHAGEN – For patients with active psoriatic arthritis for whom tumor necrosis factor (TNF) inhibitors failed to produce an adequate response, use of the dual interleukin-17 (IL-17) inhibitor bimekizumab (Bimzelx) was associated with significant improvement in joint, skin, and health-related quality-of-life parameters, compared with placebo, reported investigators in the phase 3, double-blind, randomized BE COMPLETE trial.

The primary endpoint, which was the percentage of patients who had 50% improvement in American College of Rheumatology response criteria (ACR50) at 16 weeks, was achieved in 43.4% of patients assigned to receive bimekizumab 160 mg every 4 weeks, compared with 6.8% among patients who received placebo, reported Joseph F. Merola, MD, a dermatologist and rheumatologist at Brigham and Women’s Hospital in Boston.

Neil Osterweil/Medscape

“The high-level and exciting take-home [message is] that BE COMPLETE did meet all primary and all ranked secondary endpoints at week 16,” he said at the annual European Congress of Rheumatology.

Also at the congress, Iain McInnes, MD, PhD, of the Institute of Infection, Immunity, and Inflammation at the University of Glasgow, Scotland, presented data from a second phase 3, double-blind, randomized trial called BE OPTIMAL that showed similar benefits for patients with psoriatic arthritis who had not previously received biologic disease-modifying antirheumatic drugs.

Neil Osterweil/Medscape

“This is a new mode of action, inhibiting two cytokines simultaneously,” he said in a late-breaking oral abstract session.

As previously reported by this news organization, use of bimekizumab led to rapid reductions in signs and symptoms of radiographic axial spondyloarthritis in the phase 3 trial called BE MOBILE 2.

Bimekizumab is a monoclonal immunoglobulin G1 antibody that selectively inhibits IL-17A and IL-17F. It is approved in the European Union for treating adults with moderate to severe plaque psoriasis.
 

BE COMPLETE efficacy

Inclusion criteria comprised adult-onset psoriatic arthritis meeting Classification Criteria for Psoriatic Arthritis (CASPAR) for at least 6 months; tender and swollen joint counts of at least 3/68; one or more active psoriatic lesions; and/or a documented history of psoriasis characterized by intolerance to one or two TNF inhibitors or failure of TNF inhibitors. Patients were randomly assigned in a 2:1 ratio to receive either bimekizumab 160 mg every 4 weeks (n = 267) or placebo (n = 133) for 16 weeks.

Some participants are being followed in the extension BE VITAL study, which will evaluate response to treatment and long-term safety. Patients who do enroll in the extension study will be followed for safety for a period of 20 weeks after the last dose.

As noted before, the trial met its primary endpoint of a significant improvement over placebo in ACR50 (hazard ratio, 11.1; P < .001).

In addition, the trial met all ranked secondary endpoints, including the Health Assessment Questionnaire–Disability Index change from baseline, 90% improvement in the Psoriasis Area and Severity Index (PASI90), Short-Form 36-Item Health Survey, and minimal disease activity (P < .001 for all comparisons).

Improvement with bimekizumab was rapid; curves began to separate from placebo by week 4, Dr. Merola said.

BE OPTIMAL efficacy

In this study, which had the same eligibility criteria as BE COMPLETE, patients were randomly assigned in a 2:3:1 ratio to receive 16 weeks of treatment with either placebo, bimekizumab 160 mg every 4 weeks, or adalimumab 40 mg every 2 weeks as a reference treatment.

This trial also met its primary and ranked secondary endpoints, which were similar to those of BE COMPLETE but also included measures of pooled resolution of enthesitis and dactylitis and change from baseline in van der Heijde modified total Sharp score (P < .001 for all comparisons).

In all, 43.9% of patients who received bimekizumab and 45.7% who received adalimumab achieved ACR50 at week 16, compared with 10% of patients who received placebo. The difference between the placebo and bimekizumab groups was significant (P < .001).
 

Safety

More patients who received the two active agents in this trial had treatment-emergent adverse events (TEAEs) in comparison with those in the placebo arm, but the incidence of serious TEAEs was less than 2% in each arm.

The most frequent events were nasopharyngitis, upper respiratory tract infection, headache, diarrhea, and hypertension.

Patients tolerated bimekizumab well, and there were no unexpected safety signals, Dr. McInnes said.
 

Clues to efficacy

In the question-and-answer session following Dr. McInnes’ presentation, Ronald Van Vollenhoven, MD, of the University of Amsterdam, said, “I have a question that is sort of generic in studies of psoriatic arthritis, so it does not only apply to this study, but the skin responses seem to be excellent – PASI90 sounds wonderful – but given that this is the case, is it reasonable to claim that the study is double-blinded in respect to the joints?”

Dr. McInnes replied that while he has considered this conundrum for many years in trials of drugs for psoriatic arthritis, “it doesn’t seem to be a major determinant of the outcome.”

The studies were supported by UCB Pharma. Dr. Merola and Dr. McInnes have consulted for UCB and other pharmaceutical companies that market drugs for psoriatic arthritis and psoriasis. Dr. Van Vollenhoven has received research support, has consulted for, and has spoken on behalf of UCB and other pharmaceutical companies.

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

As the use of biologics for dermatologic conditions has increased, so have questions from patients about their safety during pregnancy and lactation, their effects on fertility, and potential effects on the developing fetus and the child’s development.

“I get asked a lot about fertility,” Vivian Shi, MD, associate professor of dermatology at the University of Arkansas, Little Rock, said at MedscapeLive’s Women’s and Pediatric Dermatology Seminar. Patients want to know, she said, if they go on a specific drug, whether it will affect their chances of conceiving and what else they need to know about safety.

She told the audience what she tells her patients: The answers are not complete but are evolving at a steady pace.

“Putting this talk together was kind of like a scavenger hunt,” said Dr. Shi, who gathered data from pregnancy exposure registries, published research, the Food and Drug Administration, and other sources on biologics. As more studies emerge each year, she said, recommendations will become stronger for considering treatment by certain biological drugs, taking into account effects on fertility, pregnancy, lactation, and the infant.

Among the biologics commonly used in dermatology are:

• Tumor necrosis factor (TNF) inhibitors (etanercept, adalimumab, infliximab, certolizumab).
• Interleukin (IL)–12 and -23 antagonist (ustekinumab).
• IL-17 antagonists (ixekizumab, secukinumab, brodalumab).
• IL-23 antagonists (risankizumab, tildrakizumab, guselkumab).
• IL-4, -13 antagonist (dupilumab) and IL-13 antagonist (tralokinumab).
• CD20-directed cytolytic antibody (rituximab).

To help with decision-making, Dr. Shi discussed the relatively new FDA labeling regulations as well as pregnancy exposure registries, research studies, and recommendations.
 

FDA pregnancy risk summaries

Under the previous system of classification of drugs in pregnancy, the FDA rated drugs as A, B, C, D, X. These categories ranged from showing no risks to the fetus to clear risk, but were oversimplistic and confusing, Dr. Shi said. Category C was especially confusing, as a drug with no animal or human data was put in the same category as a drug with adverse fetal effects on animals, she noted.

However, effective June 30, 2015, the FDA replaced pregnancy categories with risk summaries by medication. As of June, 2020, all prescription drugs were to remove pregnancy letter labeling. The risk summaries note human data when they are available and also note when no data are available. This information, Dr. Shi said, originates from many sources, including studies published in the medical literature, postmarketing studies conducted by companies, and pregnancy exposure registries, conducted by some companies and others. The FDA does not endorse any specific registries, but does post a list of such registries. Another helpful resource, she said, is Mother to Baby, a service of the nonprofit Organization of Teratology Information Specialists (OTIS).



Known, not known

Citing published literature, Dr. Shi said that TNF inhibitors have the most robust safety data from preconception to after birth. Less is known, she said, about the reproductive safety effects of other biologics used for dermatologic conditions, as they are newer than the anti-TNF medicines.

She reviewed a variety of research studies evaluating the safety of biologics during pregnancy and beyond. Highlights include results from a large registry, the Psoriasis Longitudinal Assessment and Registry (PSOLAR), of 298 pregnancies in about 220 women from 2007 to 2019, looking at 13 different biologics. The overall and live-birth outcomes in the women on biologics for psoriasis were similar to those for the general population and the rate of congenital anomalies was 0.8%, researchers reported in 2021, lower than the generally cited annual figure of U.S. births.

Studies evaluating biologics for nondermatologic conditions suggest safety. A prospective cohort study of women who took adalimumab in pregnancy (for rheumatoid arthritis or Crohn’s disease) found no increased risk for birth defects. In another study looking at women who were breastfeeding, researchers found no increased risk of infections or delay in developmental milestones in the children of women taking biologics for inflammatory bowel disease, compared with those not on the medications.

A report using data from the World Health Organization concludes that dupilumab appears to be safe during pregnancy, based on an evaluation of 36 pregnancy-related reports among more than 37,000 unique adverse event reports related to dupilumab in a global database.

Recommendations about biologic use from different organizations don’t always mesh, Dr. Shi said, noting that European guidelines tend to be stricter, as some reviews show.

If a mother is exposed to any biologic therapy other than certolizumab during the third trimester, after 27 weeks, Dr. Shi said, “you want to consider avoiding a live vaccine for the first 6 months of the baby’s life.” It turns out, she said, the only recommended live vaccine during that period is the rotavirus vaccine, and she suggests doctors recommend postponing that one until the babies are older if women have been on biologics other than certolizumab.

Her other take-home messages: TNF inhibitors have the most robust safety data from before conception through lactation. Under current guidelines, certolizumab is viewed as the safest to use throughout pregnancy. Dr. Shi’s message to her colleagues fielding the same questions she gets from patients: “There is more data coming out every year. Ultimately, we will have better information to inform our patients.”

At the conference, Lawrence F. Eichenfield, MD, a course director and professor of dermatology and pediatrics at the University of California, San Diego and Rady Children’s Hospital San Diego, encouraged Dr. Shi to write up her presentation as a resource for other dermatologists – which she said is in progress.

Medscape Live and this news organization are owned by the same parent company. Dr. Shi disclosed consulting and investigative and research funding from several pharmaceutical firms, but not directly related to the content of her presentation.

As the use of biologics for dermatologic conditions has increased, so have questions from patients about their safety during pregnancy and lactation, their effects on fertility, and potential effects on the developing fetus and the child’s development.

“I get asked a lot about fertility,” Vivian Shi, MD, associate professor of dermatology at the University of Arkansas, Little Rock, said at MedscapeLive’s Women’s and Pediatric Dermatology Seminar. Patients want to know, she said, if they go on a specific drug, whether it will affect their chances of conceiving and what else they need to know about safety.

She told the audience what she tells her patients: The answers are not complete but are evolving at a steady pace.

“Putting this talk together was kind of like a scavenger hunt,” said Dr. Shi, who gathered data from pregnancy exposure registries, published research, the Food and Drug Administration, and other sources on biologics. As more studies emerge each year, she said, recommendations will become stronger for considering treatment by certain biological drugs, taking into account effects on fertility, pregnancy, lactation, and the infant.

Among the biologics commonly used in dermatology are:

• Tumor necrosis factor (TNF) inhibitors (etanercept, adalimumab, infliximab, certolizumab).
• Interleukin (IL)–12 and -23 antagonist (ustekinumab).
• IL-17 antagonists (ixekizumab, secukinumab, brodalumab).
• IL-23 antagonists (risankizumab, tildrakizumab, guselkumab).
• IL-4, -13 antagonist (dupilumab) and IL-13 antagonist (tralokinumab).
• CD20-directed cytolytic antibody (rituximab).

To help with decision-making, Dr. Shi discussed the relatively new FDA labeling regulations as well as pregnancy exposure registries, research studies, and recommendations.
 

FDA pregnancy risk summaries

Under the previous system of classification of drugs in pregnancy, the FDA rated drugs as A, B, C, D, X. These categories ranged from showing no risks to the fetus to clear risk, but were oversimplistic and confusing, Dr. Shi said. Category C was especially confusing, as a drug with no animal or human data was put in the same category as a drug with adverse fetal effects on animals, she noted.

However, effective June 30, 2015, the FDA replaced pregnancy categories with risk summaries by medication. As of June, 2020, all prescription drugs were to remove pregnancy letter labeling. The risk summaries note human data when they are available and also note when no data are available. This information, Dr. Shi said, originates from many sources, including studies published in the medical literature, postmarketing studies conducted by companies, and pregnancy exposure registries, conducted by some companies and others. The FDA does not endorse any specific registries, but does post a list of such registries. Another helpful resource, she said, is Mother to Baby, a service of the nonprofit Organization of Teratology Information Specialists (OTIS).



Known, not known

Citing published literature, Dr. Shi said that TNF inhibitors have the most robust safety data from preconception to after birth. Less is known, she said, about the reproductive safety effects of other biologics used for dermatologic conditions, as they are newer than the anti-TNF medicines.

She reviewed a variety of research studies evaluating the safety of biologics during pregnancy and beyond. Highlights include results from a large registry, the Psoriasis Longitudinal Assessment and Registry (PSOLAR), of 298 pregnancies in about 220 women from 2007 to 2019, looking at 13 different biologics. The overall and live-birth outcomes in the women on biologics for psoriasis were similar to those for the general population and the rate of congenital anomalies was 0.8%, researchers reported in 2021, lower than the generally cited annual figure of U.S. births.

Studies evaluating biologics for nondermatologic conditions suggest safety. A prospective cohort study of women who took adalimumab in pregnancy (for rheumatoid arthritis or Crohn’s disease) found no increased risk for birth defects. In another study looking at women who were breastfeeding, researchers found no increased risk of infections or delay in developmental milestones in the children of women taking biologics for inflammatory bowel disease, compared with those not on the medications.

A report using data from the World Health Organization concludes that dupilumab appears to be safe during pregnancy, based on an evaluation of 36 pregnancy-related reports among more than 37,000 unique adverse event reports related to dupilumab in a global database.

Recommendations about biologic use from different organizations don’t always mesh, Dr. Shi said, noting that European guidelines tend to be stricter, as some reviews show.

If a mother is exposed to any biologic therapy other than certolizumab during the third trimester, after 27 weeks, Dr. Shi said, “you want to consider avoiding a live vaccine for the first 6 months of the baby’s life.” It turns out, she said, the only recommended live vaccine during that period is the rotavirus vaccine, and she suggests doctors recommend postponing that one until the babies are older if women have been on biologics other than certolizumab.

Her other take-home messages: TNF inhibitors have the most robust safety data from before conception through lactation. Under current guidelines, certolizumab is viewed as the safest to use throughout pregnancy. Dr. Shi’s message to her colleagues fielding the same questions she gets from patients: “There is more data coming out every year. Ultimately, we will have better information to inform our patients.”

At the conference, Lawrence F. Eichenfield, MD, a course director and professor of dermatology and pediatrics at the University of California, San Diego and Rady Children’s Hospital San Diego, encouraged Dr. Shi to write up her presentation as a resource for other dermatologists – which she said is in progress.

Medscape Live and this news organization are owned by the same parent company. Dr. Shi disclosed consulting and investigative and research funding from several pharmaceutical firms, but not directly related to the content of her presentation.

As the use of biologics for dermatologic conditions has increased, so have questions from patients about their safety during pregnancy and lactation, their effects on fertility, and potential effects on the developing fetus and the child’s development.

“I get asked a lot about fertility,” Vivian Shi, MD, associate professor of dermatology at the University of Arkansas, Little Rock, said at MedscapeLive’s Women’s and Pediatric Dermatology Seminar. Patients want to know, she said, if they go on a specific drug, whether it will affect their chances of conceiving and what else they need to know about safety.

She told the audience what she tells her patients: The answers are not complete but are evolving at a steady pace.

“Putting this talk together was kind of like a scavenger hunt,” said Dr. Shi, who gathered data from pregnancy exposure registries, published research, the Food and Drug Administration, and other sources on biologics. As more studies emerge each year, she said, recommendations will become stronger for considering treatment by certain biological drugs, taking into account effects on fertility, pregnancy, lactation, and the infant.

Among the biologics commonly used in dermatology are:

• Tumor necrosis factor (TNF) inhibitors (etanercept, adalimumab, infliximab, certolizumab).
• Interleukin (IL)–12 and -23 antagonist (ustekinumab).
• IL-17 antagonists (ixekizumab, secukinumab, brodalumab).
• IL-23 antagonists (risankizumab, tildrakizumab, guselkumab).
• IL-4, -13 antagonist (dupilumab) and IL-13 antagonist (tralokinumab).
• CD20-directed cytolytic antibody (rituximab).

To help with decision-making, Dr. Shi discussed the relatively new FDA labeling regulations as well as pregnancy exposure registries, research studies, and recommendations.
 

FDA pregnancy risk summaries

Under the previous system of classification of drugs in pregnancy, the FDA rated drugs as A, B, C, D, X. These categories ranged from showing no risks to the fetus to clear risk, but were oversimplistic and confusing, Dr. Shi said. Category C was especially confusing, as a drug with no animal or human data was put in the same category as a drug with adverse fetal effects on animals, she noted.

However, effective June 30, 2015, the FDA replaced pregnancy categories with risk summaries by medication. As of June, 2020, all prescription drugs were to remove pregnancy letter labeling. The risk summaries note human data when they are available and also note when no data are available. This information, Dr. Shi said, originates from many sources, including studies published in the medical literature, postmarketing studies conducted by companies, and pregnancy exposure registries, conducted by some companies and others. The FDA does not endorse any specific registries, but does post a list of such registries. Another helpful resource, she said, is Mother to Baby, a service of the nonprofit Organization of Teratology Information Specialists (OTIS).



Known, not known

Citing published literature, Dr. Shi said that TNF inhibitors have the most robust safety data from preconception to after birth. Less is known, she said, about the reproductive safety effects of other biologics used for dermatologic conditions, as they are newer than the anti-TNF medicines.

She reviewed a variety of research studies evaluating the safety of biologics during pregnancy and beyond. Highlights include results from a large registry, the Psoriasis Longitudinal Assessment and Registry (PSOLAR), of 298 pregnancies in about 220 women from 2007 to 2019, looking at 13 different biologics. The overall and live-birth outcomes in the women on biologics for psoriasis were similar to those for the general population and the rate of congenital anomalies was 0.8%, researchers reported in 2021, lower than the generally cited annual figure of U.S. births.

Studies evaluating biologics for nondermatologic conditions suggest safety. A prospective cohort study of women who took adalimumab in pregnancy (for rheumatoid arthritis or Crohn’s disease) found no increased risk for birth defects. In another study looking at women who were breastfeeding, researchers found no increased risk of infections or delay in developmental milestones in the children of women taking biologics for inflammatory bowel disease, compared with those not on the medications.

A report using data from the World Health Organization concludes that dupilumab appears to be safe during pregnancy, based on an evaluation of 36 pregnancy-related reports among more than 37,000 unique adverse event reports related to dupilumab in a global database.

Recommendations about biologic use from different organizations don’t always mesh, Dr. Shi said, noting that European guidelines tend to be stricter, as some reviews show.

If a mother is exposed to any biologic therapy other than certolizumab during the third trimester, after 27 weeks, Dr. Shi said, “you want to consider avoiding a live vaccine for the first 6 months of the baby’s life.” It turns out, she said, the only recommended live vaccine during that period is the rotavirus vaccine, and she suggests doctors recommend postponing that one until the babies are older if women have been on biologics other than certolizumab.

Her other take-home messages: TNF inhibitors have the most robust safety data from before conception through lactation. Under current guidelines, certolizumab is viewed as the safest to use throughout pregnancy. Dr. Shi’s message to her colleagues fielding the same questions she gets from patients: “There is more data coming out every year. Ultimately, we will have better information to inform our patients.”

At the conference, Lawrence F. Eichenfield, MD, a course director and professor of dermatology and pediatrics at the University of California, San Diego and Rady Children’s Hospital San Diego, encouraged Dr. Shi to write up her presentation as a resource for other dermatologists – which she said is in progress.

Medscape Live and this news organization are owned by the same parent company. Dr. Shi disclosed consulting and investigative and research funding from several pharmaceutical firms, but not directly related to the content of her presentation.

A host of psoriatic arthritis symptoms can be improved by the investigational interleukin (IL)-17 blocker izokibep, according to the results of a phase 2 trial presented at the annual European Congress of Rheumatology.

Around half of all participants in the trial who were treated with izokibep achieved a 50% or higher improvement in American College of Rheumatology response criteria (ACR50) at week 16, the trial’s primary endpoint. This was highly significant (P = .0003) when compared to the control group, where only 13% of patients given a placebo achieved an ACR50.

There was also a significant improvement in skin symptoms, as assessed by the Psoriasis Area and Severity Index (PASI) and resolution of enthesitis in 88% of patients given the highest dose of izokibep.

Aurelie Najm, MD, PhD, of the Institute of Infection, Immunity and Inflammation at the University of Glasgow, who tweeted about the main results, said that the data also looked “promising for the enthesitis domain” with a “safety profile similar to that observed in PsO [psoriasis].”Peter Taylor, MA, PhD, FRCP, FRCPE, of the University of Oxford in England, said: “The improvements demonstrated in arthritis, psoriasis, and enthesitis are exciting relative to responses reported for the current standard of care.”

He continued, in a statement issued jointly by Affibody, Acelyrin, and Immagene Biopharmaceuticals – the three companies assessing izokibep’s therapeutic potential – that the drug “seems promising” and that he was “eager to see its continued development for patients.”

Small and potent, a novel IL-17 inhibitor

Izokibep is an antibody mimetic that inhibits IL-17A designed to “overcome the limitations of monoclonal antibodies,” according to its developers.

Due to its small molecular size – reportedly about one-tenth of the size of a monoclonal antibody – they say that levels of high drug exposure can be achieved from a single, subcutaneous injection rather than an intravenous infusion, which is needed for monoclonal antibodies.

Moreover, izokibep’s small size means it could potentially reach target tissues “that may otherwise be inaccessible to the much larger monoclonal antibodies.” 

So far more than 300 patients have been treated with izokibep, some for up to 3 years, but not all have had psoriatic arthritis. Indeed, the drug has been tested in patients with psoriasis, and there are a few actively recruiting trials including one in ankylosing spondylitis, another in noninfective uveitis, and one in the rare and painful skin condition hidradenitis suppurativa.

Testing two doses of izokibep in psoriatic arthritis

The trial presented at the EULAR 2022 Congress tested two doses of izokibep – 40 mg and 80 mg – given by subcutaneous injection every 2 weeks – against placebo in 135 adult patients with active psoriatic arthritis. For inclusion in the trial patients had to have at least three swollen and at least three tender joints and have had an inadequate response to prior therapy including nonsteroidal anti-inflammatory drugs, conventional synthetic disease-modifying antirheumatic drugs, or tumor necrosis factor inhibitors.

Principle investigator Frank Behrens, MD, of Goethe University Frankfurt, Germany, reported that it was a multicenter effort conducted at 22 European sites with the primary endpoint being an ACR50 response at 16 weeks. This was met by 52% of patients given the 80-mg dose of izokibep, 48% of patients given the 40-mg dose of izokibep, and just 13% of patients who had been randomized to placebo.

ACR20 and ACR70 response were one of several key secondary endpoints tested, again at 16 weeks, with a respective 75%, 60%, and 20% of patients in each group achieving the lower response target and 20%, 32%, and 5%, achieving the more stringent response target.

“Izokibep demonstrated a robust efficacy in the musculoskeletal arthritic domains, but also in the extra-articular musculoskeletal domain,” Dr. Behrens said.

Not only that, but the values were “at the top end” of what’s been demonstrated for drugs currently regarded as the standard of care.

More than 80% of patients achieved a PASI75 response and 57% a PASI50 response with the two doses of izokibep, and 63%-88% achieved a resolution of enthesitis. The latter was measured using the Leeds Enthesitis Index.

There was also improvement in quality of life, measured using the Psoriatic Impact of Disease questionnaire, with a percentage increase beyond the MCID of 31%-41% with izokibep versus 12% for placebo.

“These are the first data of the phase 2 study in psoriatic arthritis,” Dr. Behrens reported.

“The safety profile was consistent with placebo,” with the only “standout aspect” being a higher number of injection-site reactions with izokibep versus placebo; but there were no serious infections, no serious adverse events,” he added.

“The interesting thing is from the preclinical research there was no dose-limiting toxicity with izokibep, therefore, I think the plan in the future is maybe to increase the dose to optimize treatment outcome based on the really robust effectiveness we see here in the first study in this clinical trial,” he said.

As a small study, stratifying results by gender wasn’t an option, Dr. Behrens noted in answering a question during the discussion period, but might be something that will be included in future and larger trials based on the post-hoc findings of other IL-17 trials.

Moving forward, the next step will involve a phase 2b/3 pivotal study which will likely include a higher dosing regimen of 160 mg once weekly alongside the twice-weekly dosing used in this trial.

Izokibep is an investigational treatment being developed by Affibody AB, Sweden, and ACELYRIN, USA. All three companies funded the phase 2 trial and were involved in the study design, conduct and reporting of results.

Dr. Behrens and Dr. Taylor were investigators in the study.

Dr. Behrens disclosed he was a shareholder of Pfizer, Sanofi, GlaxoSmithKline, Gilead Sciences, Inc. and Novartis; part of the speakers’ bureau for Amgen, Horizon, Lilly, Novartis, Pfizer, Sanofi, Genzyme, Flexion and AbbVie; a consultant of AbbVie, Boehringer Ingelheim, Flexion, Janssen, Pfizer, Sanofi, Regeneron, SUN Pharma Advanced Research, Gilead Sciences, Inc.; and had received grant or research support from Pfizer, Janssen, Chugai, Celgene and Roche

Dr. Taylor acknowledged grant or research support from: Celgene and Galapagos, and acted as a consultant for AbbVie, Biogen, Bristol Myers Squibb, Fresenius, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, Nordic Pharma, Pfizer, Roche, Sanofi and UCB.
 

A host of psoriatic arthritis symptoms can be improved by the investigational interleukin (IL)-17 blocker izokibep, according to the results of a phase 2 trial presented at the annual European Congress of Rheumatology.

Around half of all participants in the trial who were treated with izokibep achieved a 50% or higher improvement in American College of Rheumatology response criteria (ACR50) at week 16, the trial’s primary endpoint. This was highly significant (P = .0003) when compared to the control group, where only 13% of patients given a placebo achieved an ACR50.

There was also a significant improvement in skin symptoms, as assessed by the Psoriasis Area and Severity Index (PASI) and resolution of enthesitis in 88% of patients given the highest dose of izokibep.

Aurelie Najm, MD, PhD, of the Institute of Infection, Immunity and Inflammation at the University of Glasgow, who tweeted about the main results, said that the data also looked “promising for the enthesitis domain” with a “safety profile similar to that observed in PsO [psoriasis].”Peter Taylor, MA, PhD, FRCP, FRCPE, of the University of Oxford in England, said: “The improvements demonstrated in arthritis, psoriasis, and enthesitis are exciting relative to responses reported for the current standard of care.”

He continued, in a statement issued jointly by Affibody, Acelyrin, and Immagene Biopharmaceuticals – the three companies assessing izokibep’s therapeutic potential – that the drug “seems promising” and that he was “eager to see its continued development for patients.”

Small and potent, a novel IL-17 inhibitor

Izokibep is an antibody mimetic that inhibits IL-17A designed to “overcome the limitations of monoclonal antibodies,” according to its developers.

Due to its small molecular size – reportedly about one-tenth of the size of a monoclonal antibody – they say that levels of high drug exposure can be achieved from a single, subcutaneous injection rather than an intravenous infusion, which is needed for monoclonal antibodies.

Moreover, izokibep’s small size means it could potentially reach target tissues “that may otherwise be inaccessible to the much larger monoclonal antibodies.” 

So far more than 300 patients have been treated with izokibep, some for up to 3 years, but not all have had psoriatic arthritis. Indeed, the drug has been tested in patients with psoriasis, and there are a few actively recruiting trials including one in ankylosing spondylitis, another in noninfective uveitis, and one in the rare and painful skin condition hidradenitis suppurativa.

Testing two doses of izokibep in psoriatic arthritis

The trial presented at the EULAR 2022 Congress tested two doses of izokibep – 40 mg and 80 mg – given by subcutaneous injection every 2 weeks – against placebo in 135 adult patients with active psoriatic arthritis. For inclusion in the trial patients had to have at least three swollen and at least three tender joints and have had an inadequate response to prior therapy including nonsteroidal anti-inflammatory drugs, conventional synthetic disease-modifying antirheumatic drugs, or tumor necrosis factor inhibitors.

Principle investigator Frank Behrens, MD, of Goethe University Frankfurt, Germany, reported that it was a multicenter effort conducted at 22 European sites with the primary endpoint being an ACR50 response at 16 weeks. This was met by 52% of patients given the 80-mg dose of izokibep, 48% of patients given the 40-mg dose of izokibep, and just 13% of patients who had been randomized to placebo.

ACR20 and ACR70 response were one of several key secondary endpoints tested, again at 16 weeks, with a respective 75%, 60%, and 20% of patients in each group achieving the lower response target and 20%, 32%, and 5%, achieving the more stringent response target.

“Izokibep demonstrated a robust efficacy in the musculoskeletal arthritic domains, but also in the extra-articular musculoskeletal domain,” Dr. Behrens said.

Not only that, but the values were “at the top end” of what’s been demonstrated for drugs currently regarded as the standard of care.

More than 80% of patients achieved a PASI75 response and 57% a PASI50 response with the two doses of izokibep, and 63%-88% achieved a resolution of enthesitis. The latter was measured using the Leeds Enthesitis Index.

There was also improvement in quality of life, measured using the Psoriatic Impact of Disease questionnaire, with a percentage increase beyond the MCID of 31%-41% with izokibep versus 12% for placebo.

“These are the first data of the phase 2 study in psoriatic arthritis,” Dr. Behrens reported.

“The safety profile was consistent with placebo,” with the only “standout aspect” being a higher number of injection-site reactions with izokibep versus placebo; but there were no serious infections, no serious adverse events,” he added.

“The interesting thing is from the preclinical research there was no dose-limiting toxicity with izokibep, therefore, I think the plan in the future is maybe to increase the dose to optimize treatment outcome based on the really robust effectiveness we see here in the first study in this clinical trial,” he said.

As a small study, stratifying results by gender wasn’t an option, Dr. Behrens noted in answering a question during the discussion period, but might be something that will be included in future and larger trials based on the post-hoc findings of other IL-17 trials.

Moving forward, the next step will involve a phase 2b/3 pivotal study which will likely include a higher dosing regimen of 160 mg once weekly alongside the twice-weekly dosing used in this trial.

Izokibep is an investigational treatment being developed by Affibody AB, Sweden, and ACELYRIN, USA. All three companies funded the phase 2 trial and were involved in the study design, conduct and reporting of results.

Dr. Behrens and Dr. Taylor were investigators in the study.

Dr. Behrens disclosed he was a shareholder of Pfizer, Sanofi, GlaxoSmithKline, Gilead Sciences, Inc. and Novartis; part of the speakers’ bureau for Amgen, Horizon, Lilly, Novartis, Pfizer, Sanofi, Genzyme, Flexion and AbbVie; a consultant of AbbVie, Boehringer Ingelheim, Flexion, Janssen, Pfizer, Sanofi, Regeneron, SUN Pharma Advanced Research, Gilead Sciences, Inc.; and had received grant or research support from Pfizer, Janssen, Chugai, Celgene and Roche

Dr. Taylor acknowledged grant or research support from: Celgene and Galapagos, and acted as a consultant for AbbVie, Biogen, Bristol Myers Squibb, Fresenius, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, Nordic Pharma, Pfizer, Roche, Sanofi and UCB.
 

A host of psoriatic arthritis symptoms can be improved by the investigational interleukin (IL)-17 blocker izokibep, according to the results of a phase 2 trial presented at the annual European Congress of Rheumatology.

Around half of all participants in the trial who were treated with izokibep achieved a 50% or higher improvement in American College of Rheumatology response criteria (ACR50) at week 16, the trial’s primary endpoint. This was highly significant (P = .0003) when compared to the control group, where only 13% of patients given a placebo achieved an ACR50.

There was also a significant improvement in skin symptoms, as assessed by the Psoriasis Area and Severity Index (PASI) and resolution of enthesitis in 88% of patients given the highest dose of izokibep.

Aurelie Najm, MD, PhD, of the Institute of Infection, Immunity and Inflammation at the University of Glasgow, who tweeted about the main results, said that the data also looked “promising for the enthesitis domain” with a “safety profile similar to that observed in PsO [psoriasis].”Peter Taylor, MA, PhD, FRCP, FRCPE, of the University of Oxford in England, said: “The improvements demonstrated in arthritis, psoriasis, and enthesitis are exciting relative to responses reported for the current standard of care.”

He continued, in a statement issued jointly by Affibody, Acelyrin, and Immagene Biopharmaceuticals – the three companies assessing izokibep’s therapeutic potential – that the drug “seems promising” and that he was “eager to see its continued development for patients.”

Small and potent, a novel IL-17 inhibitor

Izokibep is an antibody mimetic that inhibits IL-17A designed to “overcome the limitations of monoclonal antibodies,” according to its developers.

Due to its small molecular size – reportedly about one-tenth of the size of a monoclonal antibody – they say that levels of high drug exposure can be achieved from a single, subcutaneous injection rather than an intravenous infusion, which is needed for monoclonal antibodies.

Moreover, izokibep’s small size means it could potentially reach target tissues “that may otherwise be inaccessible to the much larger monoclonal antibodies.” 

So far more than 300 patients have been treated with izokibep, some for up to 3 years, but not all have had psoriatic arthritis. Indeed, the drug has been tested in patients with psoriasis, and there are a few actively recruiting trials including one in ankylosing spondylitis, another in noninfective uveitis, and one in the rare and painful skin condition hidradenitis suppurativa.

Testing two doses of izokibep in psoriatic arthritis

The trial presented at the EULAR 2022 Congress tested two doses of izokibep – 40 mg and 80 mg – given by subcutaneous injection every 2 weeks – against placebo in 135 adult patients with active psoriatic arthritis. For inclusion in the trial patients had to have at least three swollen and at least three tender joints and have had an inadequate response to prior therapy including nonsteroidal anti-inflammatory drugs, conventional synthetic disease-modifying antirheumatic drugs, or tumor necrosis factor inhibitors.

Principle investigator Frank Behrens, MD, of Goethe University Frankfurt, Germany, reported that it was a multicenter effort conducted at 22 European sites with the primary endpoint being an ACR50 response at 16 weeks. This was met by 52% of patients given the 80-mg dose of izokibep, 48% of patients given the 40-mg dose of izokibep, and just 13% of patients who had been randomized to placebo.

ACR20 and ACR70 response were one of several key secondary endpoints tested, again at 16 weeks, with a respective 75%, 60%, and 20% of patients in each group achieving the lower response target and 20%, 32%, and 5%, achieving the more stringent response target.

“Izokibep demonstrated a robust efficacy in the musculoskeletal arthritic domains, but also in the extra-articular musculoskeletal domain,” Dr. Behrens said.

Not only that, but the values were “at the top end” of what’s been demonstrated for drugs currently regarded as the standard of care.

More than 80% of patients achieved a PASI75 response and 57% a PASI50 response with the two doses of izokibep, and 63%-88% achieved a resolution of enthesitis. The latter was measured using the Leeds Enthesitis Index.

There was also improvement in quality of life, measured using the Psoriatic Impact of Disease questionnaire, with a percentage increase beyond the MCID of 31%-41% with izokibep versus 12% for placebo.

“These are the first data of the phase 2 study in psoriatic arthritis,” Dr. Behrens reported.

“The safety profile was consistent with placebo,” with the only “standout aspect” being a higher number of injection-site reactions with izokibep versus placebo; but there were no serious infections, no serious adverse events,” he added.

“The interesting thing is from the preclinical research there was no dose-limiting toxicity with izokibep, therefore, I think the plan in the future is maybe to increase the dose to optimize treatment outcome based on the really robust effectiveness we see here in the first study in this clinical trial,” he said.

As a small study, stratifying results by gender wasn’t an option, Dr. Behrens noted in answering a question during the discussion period, but might be something that will be included in future and larger trials based on the post-hoc findings of other IL-17 trials.

Moving forward, the next step will involve a phase 2b/3 pivotal study which will likely include a higher dosing regimen of 160 mg once weekly alongside the twice-weekly dosing used in this trial.

Izokibep is an investigational treatment being developed by Affibody AB, Sweden, and ACELYRIN, USA. All three companies funded the phase 2 trial and were involved in the study design, conduct and reporting of results.

Dr. Behrens and Dr. Taylor were investigators in the study.

Dr. Behrens disclosed he was a shareholder of Pfizer, Sanofi, GlaxoSmithKline, Gilead Sciences, Inc. and Novartis; part of the speakers’ bureau for Amgen, Horizon, Lilly, Novartis, Pfizer, Sanofi, Genzyme, Flexion and AbbVie; a consultant of AbbVie, Boehringer Ingelheim, Flexion, Janssen, Pfizer, Sanofi, Regeneron, SUN Pharma Advanced Research, Gilead Sciences, Inc.; and had received grant or research support from Pfizer, Janssen, Chugai, Celgene and Roche

Dr. Taylor acknowledged grant or research support from: Celgene and Galapagos, and acted as a consultant for AbbVie, Biogen, Bristol Myers Squibb, Fresenius, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, Nordic Pharma, Pfizer, Roche, Sanofi and UCB.
 

Monitoring serum brodalumab levels may help doctors treat some patients with psoriasis more effectively, the authors of a small Danish case series report.

In a study of patients with psoriasis who had previously failed treatment with interleukin-17 receptor A inhibitor therapy, “all patients with quantifiable levels of brodalumab after 12 weeks of therapy experienced PASI reductions” and subquantifiable brodalumab levels were associated with a lack of response after 12 weeks, they wrote in JAMA Dermatology.

Lead study author Christian Enevold, PhD, a researcher at the Institute for Inflammation Research at Copenhagen University Hospital, and colleagues monitored patients with plaque psoriasis who had not improved with previous IL-17A inhibitor therapy, to evaluate whether trough levels and antidrug antibodies were associated with clinical response in this group of patients.

The 20 consecutive adult patients were treated at two academic hospital dermatology clinics between 2018 and 2020 and ranged in age from 19 to 66 years; 13 were male. At baseline, their weight ranged from 59 to 182 kg (median, 103 kg), their body mass index (BMI) ranged from 20 to 50 (median, 32), and their Psoriasis Area and Severity Index (PASI) scores ranged from 7 to 26 (median, 13). All had failed treatment with at least one IL-17A inhibitor, and 90% had failed treatment with at least one tumor necrosis factor–alpha or IL-12/-23 inhibitor.

Patients stopped taking systemic psoriasis therapies for 4 weeks before entering the study, then received subcutaneous injections of 210 mg of the IL-17A inhibitor brodalumab (Siliq) at weeks 0, 1, 2, and every 2 weeks thereafter. Patients whose PASI scores did not improve at least 75% from baseline (PASI 75) after 12 weeks of brodalumab discontinued treatment and left the study, while those who maintained PASI 75 were monitored for up to 52 weeks.

The researchers used assays to compare decreases in PASI score with brodalumab levels as well as with antibrodalumab antibodies at 12 weeks, and determined the following:

• Participants with quantifiable brodalumab levels (≥ 0.05 mcg/mL) showed a greater drop in PASI scores (median, 93%; range, 61%-100%) than those without quantifiable brodalumab levels (median, −3; range, −49% to 94%) (P = .006).
• Four of 5 patients (80%) who did not achieve a PASI 75, compared with 3 of 14 PASI 75 responders (21%), had drug levels too low to be measured (< 0.05 mcg/mL).
• The eight patients who did not have obesity (BMI < 30) had PASI reductions of at least 77%, and seven of the eight patients (88%) had quantifiable brodalumab levels.
• Six of the 12 patients with obesity (BMI ≥ 30) had brodalumab levels too low to be measured. Of those, four had increased PASI after 12 weeks of treatment. For all patients with obesity with quantifiable brodalumab levels, PASI scores dropped by at least 61% after 12 weeks.
• Five of the 12 (42%) patients with obesity versus 7 of the 8 (88%) patients without obesity had quantifiable brodalumab levels.
• None of the seven patients (35%) with subquantifiable drug levels after 12 weeks remained PASI responders.
• No antibrodalumab antibodies were detected in any serum samples.

The authors acknowledged that there were limitations of the study, including its retrospective design and restriction to the few available participants with a history of treatment failure.

Dr. Han

George Han, MD, PhD, associate professor of dermatology at Hofstra University, Hempstead, N.Y., said in an interview that he found the study interesting. “The authors did an admirable job looking at many factors to try to understand response to treatment in a challenging population of patients who had failed at least one, and in many cases, numerous, biologics from different classes.”

“The most interesting finding is that patients with higher BMIs had much higher rates of low-to-undetectable drug concentration,” said Dr. Han, who was not involved in the study. “This very practical finding could help patient care immediately. While it’s impractical to start performing assays of drug concentration in clinical practice, this finding certainly would guide my conversations with my heavier-set patients who have had multiple failures on previous biologics.

“I’m looking forward to further studies that explore this issue and provide better evidence-based guidance for treating patients who have experienced multi-biologic failure,” he added.

UC San Diego Health Sciences

Robert A. Dorschner, MD, assistant professor of dermatology at the UC San Diego Health System, also welcomed the study’s results.

“Current psoriasis treatment is based on trial-and-error application of various biologics targeting different pathways, with initial selection frequently based on insurance preference, not patient characteristics,” he said in an interview.

“Studies like this help clinicians make more informed decisions about whether a patient may benefit from a different dose or may require a different drug, and make those decisions earlier in therapy,” he said. “This can improve patient care and decrease costs associated with prolonged treatments with ineffective drugs.”

But Dr. Dorschner, who also was not involved in the study, cautions clinicians to not draw conclusions about dose adjustments from these results. “These findings need to be verified in a larger cohort,” he advised, “and they should drive future studies with larger cohorts and prospective designs.”

“The last couple of decades have seen an explosion in the availability of biologics targeting different cytokines, with significant benefits to patients,” Dr. Dorschner explained. “However, there is a dearth of information on how to choose the right biologic for a particular patient and how to assess the benefit of dose alteration versus changing the drug target. Medicine needs more studies like this one.”

Several authors of the study report financial relationships with LEO Pharma and other pharmaceutical companies. Most authors, including Dr. Enevold, reported no relevant financial relationships. Dr. Dorschner reported no relevant financial relationships. Dr. Han reported financial relationships with pharmaceutical companies not involved in the study. The study was funded by LEO Pharma and the Danish Biotechnology Program.
 

Monitoring serum brodalumab levels may help doctors treat some patients with psoriasis more effectively, the authors of a small Danish case series report.

In a study of patients with psoriasis who had previously failed treatment with interleukin-17 receptor A inhibitor therapy, “all patients with quantifiable levels of brodalumab after 12 weeks of therapy experienced PASI reductions” and subquantifiable brodalumab levels were associated with a lack of response after 12 weeks, they wrote in JAMA Dermatology.

Lead study author Christian Enevold, PhD, a researcher at the Institute for Inflammation Research at Copenhagen University Hospital, and colleagues monitored patients with plaque psoriasis who had not improved with previous IL-17A inhibitor therapy, to evaluate whether trough levels and antidrug antibodies were associated with clinical response in this group of patients.

The 20 consecutive adult patients were treated at two academic hospital dermatology clinics between 2018 and 2020 and ranged in age from 19 to 66 years; 13 were male. At baseline, their weight ranged from 59 to 182 kg (median, 103 kg), their body mass index (BMI) ranged from 20 to 50 (median, 32), and their Psoriasis Area and Severity Index (PASI) scores ranged from 7 to 26 (median, 13). All had failed treatment with at least one IL-17A inhibitor, and 90% had failed treatment with at least one tumor necrosis factor–alpha or IL-12/-23 inhibitor.

Patients stopped taking systemic psoriasis therapies for 4 weeks before entering the study, then received subcutaneous injections of 210 mg of the IL-17A inhibitor brodalumab (Siliq) at weeks 0, 1, 2, and every 2 weeks thereafter. Patients whose PASI scores did not improve at least 75% from baseline (PASI 75) after 12 weeks of brodalumab discontinued treatment and left the study, while those who maintained PASI 75 were monitored for up to 52 weeks.

The researchers used assays to compare decreases in PASI score with brodalumab levels as well as with antibrodalumab antibodies at 12 weeks, and determined the following:

• Participants with quantifiable brodalumab levels (≥ 0.05 mcg/mL) showed a greater drop in PASI scores (median, 93%; range, 61%-100%) than those without quantifiable brodalumab levels (median, −3; range, −49% to 94%) (P = .006).
• Four of 5 patients (80%) who did not achieve a PASI 75, compared with 3 of 14 PASI 75 responders (21%), had drug levels too low to be measured (< 0.05 mcg/mL).
• The eight patients who did not have obesity (BMI < 30) had PASI reductions of at least 77%, and seven of the eight patients (88%) had quantifiable brodalumab levels.
• Six of the 12 patients with obesity (BMI ≥ 30) had brodalumab levels too low to be measured. Of those, four had increased PASI after 12 weeks of treatment. For all patients with obesity with quantifiable brodalumab levels, PASI scores dropped by at least 61% after 12 weeks.
• Five of the 12 (42%) patients with obesity versus 7 of the 8 (88%) patients without obesity had quantifiable brodalumab levels.
• None of the seven patients (35%) with subquantifiable drug levels after 12 weeks remained PASI responders.
• No antibrodalumab antibodies were detected in any serum samples.

The authors acknowledged that there were limitations of the study, including its retrospective design and restriction to the few available participants with a history of treatment failure.

Dr. Han

George Han, MD, PhD, associate professor of dermatology at Hofstra University, Hempstead, N.Y., said in an interview that he found the study interesting. “The authors did an admirable job looking at many factors to try to understand response to treatment in a challenging population of patients who had failed at least one, and in many cases, numerous, biologics from different classes.”

“The most interesting finding is that patients with higher BMIs had much higher rates of low-to-undetectable drug concentration,” said Dr. Han, who was not involved in the study. “This very practical finding could help patient care immediately. While it’s impractical to start performing assays of drug concentration in clinical practice, this finding certainly would guide my conversations with my heavier-set patients who have had multiple failures on previous biologics.

“I’m looking forward to further studies that explore this issue and provide better evidence-based guidance for treating patients who have experienced multi-biologic failure,” he added.

UC San Diego Health Sciences

Robert A. Dorschner, MD, assistant professor of dermatology at the UC San Diego Health System, also welcomed the study’s results.

“Current psoriasis treatment is based on trial-and-error application of various biologics targeting different pathways, with initial selection frequently based on insurance preference, not patient characteristics,” he said in an interview.

“Studies like this help clinicians make more informed decisions about whether a patient may benefit from a different dose or may require a different drug, and make those decisions earlier in therapy,” he said. “This can improve patient care and decrease costs associated with prolonged treatments with ineffective drugs.”

But Dr. Dorschner, who also was not involved in the study, cautions clinicians to not draw conclusions about dose adjustments from these results. “These findings need to be verified in a larger cohort,” he advised, “and they should drive future studies with larger cohorts and prospective designs.”

“The last couple of decades have seen an explosion in the availability of biologics targeting different cytokines, with significant benefits to patients,” Dr. Dorschner explained. “However, there is a dearth of information on how to choose the right biologic for a particular patient and how to assess the benefit of dose alteration versus changing the drug target. Medicine needs more studies like this one.”

Several authors of the study report financial relationships with LEO Pharma and other pharmaceutical companies. Most authors, including Dr. Enevold, reported no relevant financial relationships. Dr. Dorschner reported no relevant financial relationships. Dr. Han reported financial relationships with pharmaceutical companies not involved in the study. The study was funded by LEO Pharma and the Danish Biotechnology Program.
 

Monitoring serum brodalumab levels may help doctors treat some patients with psoriasis more effectively, the authors of a small Danish case series report.

In a study of patients with psoriasis who had previously failed treatment with interleukin-17 receptor A inhibitor therapy, “all patients with quantifiable levels of brodalumab after 12 weeks of therapy experienced PASI reductions” and subquantifiable brodalumab levels were associated with a lack of response after 12 weeks, they wrote in JAMA Dermatology.

Lead study author Christian Enevold, PhD, a researcher at the Institute for Inflammation Research at Copenhagen University Hospital, and colleagues monitored patients with plaque psoriasis who had not improved with previous IL-17A inhibitor therapy, to evaluate whether trough levels and antidrug antibodies were associated with clinical response in this group of patients.

The 20 consecutive adult patients were treated at two academic hospital dermatology clinics between 2018 and 2020 and ranged in age from 19 to 66 years; 13 were male. At baseline, their weight ranged from 59 to 182 kg (median, 103 kg), their body mass index (BMI) ranged from 20 to 50 (median, 32), and their Psoriasis Area and Severity Index (PASI) scores ranged from 7 to 26 (median, 13). All had failed treatment with at least one IL-17A inhibitor, and 90% had failed treatment with at least one tumor necrosis factor–alpha or IL-12/-23 inhibitor.

Patients stopped taking systemic psoriasis therapies for 4 weeks before entering the study, then received subcutaneous injections of 210 mg of the IL-17A inhibitor brodalumab (Siliq) at weeks 0, 1, 2, and every 2 weeks thereafter. Patients whose PASI scores did not improve at least 75% from baseline (PASI 75) after 12 weeks of brodalumab discontinued treatment and left the study, while those who maintained PASI 75 were monitored for up to 52 weeks.

The researchers used assays to compare decreases in PASI score with brodalumab levels as well as with antibrodalumab antibodies at 12 weeks, and determined the following:

• Participants with quantifiable brodalumab levels (≥ 0.05 mcg/mL) showed a greater drop in PASI scores (median, 93%; range, 61%-100%) than those without quantifiable brodalumab levels (median, −3; range, −49% to 94%) (P = .006).
• Four of 5 patients (80%) who did not achieve a PASI 75, compared with 3 of 14 PASI 75 responders (21%), had drug levels too low to be measured (< 0.05 mcg/mL).
• The eight patients who did not have obesity (BMI < 30) had PASI reductions of at least 77%, and seven of the eight patients (88%) had quantifiable brodalumab levels.
• Six of the 12 patients with obesity (BMI ≥ 30) had brodalumab levels too low to be measured. Of those, four had increased PASI after 12 weeks of treatment. For all patients with obesity with quantifiable brodalumab levels, PASI scores dropped by at least 61% after 12 weeks.
• Five of the 12 (42%) patients with obesity versus 7 of the 8 (88%) patients without obesity had quantifiable brodalumab levels.
• None of the seven patients (35%) with subquantifiable drug levels after 12 weeks remained PASI responders.
• No antibrodalumab antibodies were detected in any serum samples.

The authors acknowledged that there were limitations of the study, including its retrospective design and restriction to the few available participants with a history of treatment failure.

Dr. Han

George Han, MD, PhD, associate professor of dermatology at Hofstra University, Hempstead, N.Y., said in an interview that he found the study interesting. “The authors did an admirable job looking at many factors to try to understand response to treatment in a challenging population of patients who had failed at least one, and in many cases, numerous, biologics from different classes.”

“The most interesting finding is that patients with higher BMIs had much higher rates of low-to-undetectable drug concentration,” said Dr. Han, who was not involved in the study. “This very practical finding could help patient care immediately. While it’s impractical to start performing assays of drug concentration in clinical practice, this finding certainly would guide my conversations with my heavier-set patients who have had multiple failures on previous biologics.

“I’m looking forward to further studies that explore this issue and provide better evidence-based guidance for treating patients who have experienced multi-biologic failure,” he added.

UC San Diego Health Sciences

Robert A. Dorschner, MD, assistant professor of dermatology at the UC San Diego Health System, also welcomed the study’s results.

“Current psoriasis treatment is based on trial-and-error application of various biologics targeting different pathways, with initial selection frequently based on insurance preference, not patient characteristics,” he said in an interview.

“Studies like this help clinicians make more informed decisions about whether a patient may benefit from a different dose or may require a different drug, and make those decisions earlier in therapy,” he said. “This can improve patient care and decrease costs associated with prolonged treatments with ineffective drugs.”

But Dr. Dorschner, who also was not involved in the study, cautions clinicians to not draw conclusions about dose adjustments from these results. “These findings need to be verified in a larger cohort,” he advised, “and they should drive future studies with larger cohorts and prospective designs.”

“The last couple of decades have seen an explosion in the availability of biologics targeting different cytokines, with significant benefits to patients,” Dr. Dorschner explained. “However, there is a dearth of information on how to choose the right biologic for a particular patient and how to assess the benefit of dose alteration versus changing the drug target. Medicine needs more studies like this one.”

Several authors of the study report financial relationships with LEO Pharma and other pharmaceutical companies. Most authors, including Dr. Enevold, reported no relevant financial relationships. Dr. Dorschner reported no relevant financial relationships. Dr. Han reported financial relationships with pharmaceutical companies not involved in the study. The study was funded by LEO Pharma and the Danish Biotechnology Program.