Exposure-Response Relationships in Ulcerative Colitis Clinical Programs -  

summary

• The company cannot recommend any practices, procedures, or usage that deviate from the approved labeling.
• Analysis of pooled data from the QUASAR program through maintenance week 44 found that higher serum guselkumab concentrations were associated with greater rates of specific efficacy outcomes. It was also reported that serum guselkumab levels were not associated with infections, serious infections, serious adverse events, or abnormal liver function tests.¹
• A post-hoc analysis was conducted to compare predicted serum guselkumab pharmacokinetic (PK) exposure between intravenous (QUASAR, IV) and subcutaneous (ASTRO, SC) induction regimens. Results are summarized below.²

CLINICAL DATA

PK and Exposure-Response Analysis

Rubin et al (2026)¹ evaluated the covariate impacts on PK and exposure-response
(E-R) of TREMFYA SC maintenance regimens (100 mg every 8 weeks [Q8W] or 200 mg every 4 weeks [Q4W]) using data from the phase 2/3 QUASAR program in patients with moderately to severely active UC.

Study Design/Methods

• Patients had received ≥1 TREMFYA dose and had data from ≥1 PK measurement (as well as efficacy data for E-R assessment).
• Population PK modeling was performed using pooled QUASAR PK data through maintenance week 44.
• Relationships between exposure and efficacy outcomes (eg, clinical remission, endoscopic improvement, histologic-endoscopic mucosal improvement [HEMI]) at maintenance week 44 were explored.
• Associations between exposure and safety, covariate impacts on E-R and impacts of immunogenicity on efficacy and safety were also explored.

Results

• Higher serum guselkumab concentrations were associated with greater rates of clinical remission, endoscopic improvement, and HEMI at maintenance week 44. See Figure: Rates of Clinical Remission at Maintenance Week 44 by Serum Guselkumab Trough Quartiles and Rates of Endoscopic Improvement at Maintenance Week 44 by Serum Guselkumab Trough Quartiles and Rates of HEMI at Maintenance Week 44 by Serum Guselkumab Trough Quartiles.
• Using predicted model and stratified by extensive disease (at induction baseline) or clinical remission and endoscopic improvement status (at maintenance baseline), greater treatment outcomes were observed with TREMFYA 200 mg SC Q4W vs 100 mg SC Q8W maintenance dose, suggesting that higher exposure may benefit certain patients. See Table: Model-Predicted Clinical Remission and Endoscopic Improvement Rates at Maintenance Week 44 by Median C_trough.
• There were no associations between the serum guselkumab concentration and infections, serious infections, serious adverse events, or abnormal liver function tests.
• Use of immunosuppressants (azathioprine, methotrexate, 6-mercaptopurine) did not influence guselkumab concentrations.
• The incidence of antidrug antibodies and neutralizing antibodies to TREMFYA was low and did not impact PK, efficacy, or safety of TREMFYA.

Peyrin-Biroulet (2025)² evaluated the PK and E-R for the efficacy and safety of TREMFYA IV and SC induction formulations (QUASAR and ASTRO studies).

Study Design/Methods

• The IV induction dosing regimen for phase 2b/3 QUASAR studies included 200 mg
  Q4W ×3 and SC induction for ASTRO study included 400 mg Q4W ×3.
• Both QUASAR and ASTRO studies used the same SC maintenance dosing regimens
  (100 mg Q8W or 200 mg Q4W).
• To compare TREMFYA PK exposure following 200 mg IV vs 400 mg SC induction through week 12, individual post hoc PK parameters and patient dosing information from QUASAR and ASTRO were used to simulate concentration-time profile and calculate individual induction exposure metrics.
  • PK parameters were estimated with the established QUASAR 2-compartment linear population PK model with first-order absorption and elimination.
• For key week 12 efficacy endpoints (clinical remission, clinical response, endoscopic improvement, and HEMI), comparative graphical E-R analysis (QUASAR vs ASTRO) was conducted using overall exposure during induction (C_{ave, week 0-12}) and associated exposure quartiles from the combined study populations.

Results

• SC induction resulted in similar average serum concentrations and area under the concentration-time curve (AUC) from week 0 to week 12, lower peak concentrations at week 8, and higher trough levels at week 12 compared with IV induction. These are consistent with model predictions.
• At week 12, efficacy outcomes were comparable across TREMFYA concentration quartiles for both IV and SC induction. For details, see Figures: Clinical Response at Week 12 by GUS C_{ave, week 0-12} Quartile (μg/mL) and Clinical Remission at Week 12 by GUS
  C_{ave, week 0-12} Quartile (μg/mL), Endoscopic Improvement at Week 12 by GUS C_{ave, week 0-12} Quartile (μg/mL), and HEMI at Week 12 by GUS C_{ave, week 0-12} Quartile (μg/mL).

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on
11 September 2026.