Early use of ustekinumab levels could predict psoriasis outcomes

Early ustekinumab levels are significantly associated with a 75% reduction in Psoriasis Area and Severity Index scores from baseline, according to data from 491 adults with psoriasis.

“Evidence suggests that ustekinumab dosing is suboptimal in some patients,” because of factors including weight-based dosing and dosing intervals; therefore “individualized dose optimization and therapeutic drug monitoring (TDM) of ustekinumab may have clinical utility,” Teresa Tsakok, MRCP, of King’s College London, and colleagues wrote in JAMA Dermatology.

The researchers identified 491 adults with psoriasis who were part of the BSTOP (Biomarkers of Systemic Treatment Outcomes in Psoriasis) cohort study in the United Kingdom. Blood samples were collected during clinical reviews to assess ustekinumab levels, and primary treatment response was 75% reduction in Psoriasis Area and Severity Index (PASI 75) scores.

Ustekinumab levels measured from 1-12 weeks after the start of treatment were significantly associated with PASI 75 after 6 months (odds ratio, 1.38) after controlling for factors including baseline PASI scores, age, and ustekinumab dose. The association, however, did not hold for other PASI outcomes, including PASI 90 and PASI scores of 1.5 or less.

The participants had at least one serum sample collected at 0-56 weeks from the start of treatment and at least one PSAI score measured within the first year of treatment. The average baseline PASI score was 13.3, the average body mass index was 32 kg/m², and 65% of the patients were male.

Overall, 348 patients (71%) achieved PASI 75 within a year of starting ustekinumab. Antidrug antibodies were detected in 17 patients (3.5% of the study population), compared with a rate of 37.5% in patients from the same study cohort who were taking adalimumab, the researchers noted.

The study findings were limited by several factors, including a dropoff in patient numbers over the study period and the difficulty in accounting for the association between drug level and treatment response in a logistic regression model, the researchers said.

The results, however, suggest “that adequate drug exposure early in the treatment cycle may be particularly important in determining clinical outcome with ustekinumab,” and that “future work should focus on pharmacokinetic-pharmacodynamic modeling of the whole time course of response to ustekinumab” as a key step toward personalized treatment regimens, they concluded.

The study was supported by several entities, including the Medical Research Council (MRC), the National Institute for Health Research Biomedical Research Center and the Psoriasis Association. Dr. Tsakok had no financial conflicts to disclose and was supported by an MRC Clinical Research Training Fellowship.

SOURCE: Tsakok T et al. JAMA Dermatol. 2019 Sep 18. doi: 10.1001/jamadermatol.2019.1783.

Early ustekinumab levels are significantly associated with a 75% reduction in Psoriasis Area and Severity Index scores from baseline, according to data from 491 adults with psoriasis.

“Evidence suggests that ustekinumab dosing is suboptimal in some patients,” because of factors including weight-based dosing and dosing intervals; therefore “individualized dose optimization and therapeutic drug monitoring (TDM) of ustekinumab may have clinical utility,” Teresa Tsakok, MRCP, of King’s College London, and colleagues wrote in JAMA Dermatology.

The researchers identified 491 adults with psoriasis who were part of the BSTOP (Biomarkers of Systemic Treatment Outcomes in Psoriasis) cohort study in the United Kingdom. Blood samples were collected during clinical reviews to assess ustekinumab levels, and primary treatment response was 75% reduction in Psoriasis Area and Severity Index (PASI 75) scores.

Ustekinumab levels measured from 1-12 weeks after the start of treatment were significantly associated with PASI 75 after 6 months (odds ratio, 1.38) after controlling for factors including baseline PASI scores, age, and ustekinumab dose. The association, however, did not hold for other PASI outcomes, including PASI 90 and PASI scores of 1.5 or less.

The participants had at least one serum sample collected at 0-56 weeks from the start of treatment and at least one PSAI score measured within the first year of treatment. The average baseline PASI score was 13.3, the average body mass index was 32 kg/m², and 65% of the patients were male.

Overall, 348 patients (71%) achieved PASI 75 within a year of starting ustekinumab. Antidrug antibodies were detected in 17 patients (3.5% of the study population), compared with a rate of 37.5% in patients from the same study cohort who were taking adalimumab, the researchers noted.

The study findings were limited by several factors, including a dropoff in patient numbers over the study period and the difficulty in accounting for the association between drug level and treatment response in a logistic regression model, the researchers said.

The results, however, suggest “that adequate drug exposure early in the treatment cycle may be particularly important in determining clinical outcome with ustekinumab,” and that “future work should focus on pharmacokinetic-pharmacodynamic modeling of the whole time course of response to ustekinumab” as a key step toward personalized treatment regimens, they concluded.

The study was supported by several entities, including the Medical Research Council (MRC), the National Institute for Health Research Biomedical Research Center and the Psoriasis Association. Dr. Tsakok had no financial conflicts to disclose and was supported by an MRC Clinical Research Training Fellowship.

SOURCE: Tsakok T et al. JAMA Dermatol. 2019 Sep 18. doi: 10.1001/jamadermatol.2019.1783.

Early ustekinumab levels are significantly associated with a 75% reduction in Psoriasis Area and Severity Index scores from baseline, according to data from 491 adults with psoriasis.

“Evidence suggests that ustekinumab dosing is suboptimal in some patients,” because of factors including weight-based dosing and dosing intervals; therefore “individualized dose optimization and therapeutic drug monitoring (TDM) of ustekinumab may have clinical utility,” Teresa Tsakok, MRCP, of King’s College London, and colleagues wrote in JAMA Dermatology.

The researchers identified 491 adults with psoriasis who were part of the BSTOP (Biomarkers of Systemic Treatment Outcomes in Psoriasis) cohort study in the United Kingdom. Blood samples were collected during clinical reviews to assess ustekinumab levels, and primary treatment response was 75% reduction in Psoriasis Area and Severity Index (PASI 75) scores.

Ustekinumab levels measured from 1-12 weeks after the start of treatment were significantly associated with PASI 75 after 6 months (odds ratio, 1.38) after controlling for factors including baseline PASI scores, age, and ustekinumab dose. The association, however, did not hold for other PASI outcomes, including PASI 90 and PASI scores of 1.5 or less.

The participants had at least one serum sample collected at 0-56 weeks from the start of treatment and at least one PSAI score measured within the first year of treatment. The average baseline PASI score was 13.3, the average body mass index was 32 kg/m², and 65% of the patients were male.

Overall, 348 patients (71%) achieved PASI 75 within a year of starting ustekinumab. Antidrug antibodies were detected in 17 patients (3.5% of the study population), compared with a rate of 37.5% in patients from the same study cohort who were taking adalimumab, the researchers noted.

The study findings were limited by several factors, including a dropoff in patient numbers over the study period and the difficulty in accounting for the association between drug level and treatment response in a logistic regression model, the researchers said.

The results, however, suggest “that adequate drug exposure early in the treatment cycle may be particularly important in determining clinical outcome with ustekinumab,” and that “future work should focus on pharmacokinetic-pharmacodynamic modeling of the whole time course of response to ustekinumab” as a key step toward personalized treatment regimens, they concluded.

The study was supported by several entities, including the Medical Research Council (MRC), the National Institute for Health Research Biomedical Research Center and the Psoriasis Association. Dr. Tsakok had no financial conflicts to disclose and was supported by an MRC Clinical Research Training Fellowship.

SOURCE: Tsakok T et al. JAMA Dermatol. 2019 Sep 18. doi: 10.1001/jamadermatol.2019.1783.