This study evaluates the pharmacokinetic profile of the investigational drug over approximately 58 days, measuring key parameters including Cmax, Tmax, terminal elimination rate constant (beta), half-life (t1/2), and AUC values (AUCt and AUC∞). Safety is assessed through adverse event monitoring for approximately 72 days, with investigators determining causality between reported AEs and study treatment.

The primary endpoint was achieving ACR50 response at Week 12, defined as ≥50% improvement in tender/swollen joint counts and ≥50% improvement in 3 of 5 additional measures including physician/patient global assessments, pain score, HAQ-DI, and hsCRP. Secondary endpoints included changes in DAS28 and CDAI scores, with lower scores indicating improvement, as well as ACR20/70 responses, low disease activity (DAS28 ≤3.2 or CDAI ≤10), clinical remission (DAS28 <2.6 or CDAI ≤2.8), and HAQ-DI improvement from baseline.

Inclusion criteria require confirmed RA (1987 ACR/2010 EULAR criteria) lasting >3 months, with ≥4 swollen/tender joints (28-count), DAS28-CRP ≥3.2, and inadequate MTX response (stable dose 15-25mg/week [≥10mg/week if intolerant] for ≥4 weeks). Exclusions include prior anti-TNF use (e.g., adalimumab) or non-anti-TNF biologics/tsDMARDs (unless used <3 months without efficacy/intolerability issues).

Secondary endpoints include Week 12 changes in CDAI (sum of tender/swollen joints + patient/physician global assessments [VAS 0-10cm]; score 0-76), SDAI (CDAI+CRP; score 0-86), and DAS28-ESR (similar to DAS28-CRP but using ESR). Negative changes denote improvement. Additional measures: proportion achieving DAS28-CRP ≤3.2 (low disease activity) and American College of Rheumatology 50% (ACR50) response (≥50% improvement in joint counts + ≥3 of 5 key parameters).

In an acute in vivo model of contact hypersensitivity (CHS) mice were sensitized with fluorescein isothiocyanate (FITC) on the abdomen and challenged 6 days later with FITC on the ear,which resulted in an increase in ear swelling that was measured 24 h postchallenge. Anti-mTNF GRM ADCs were dosed at either 3 mg/kg once prior to FITC sensitization. Mice were challenged with adrenocorticotropic hormone (ACTH) 72 h following ADC dosing and plasma was collected 30 min later to assess P1NP level.

In an acute in vivo model of contact hypersensitivity (CHS) mice were sensitized with fluorescein isothiocyanate (FITC) on the abdomen and challenged 6 days later with FITC on the ear,which resulted in an increase in ear swelling that was measured 24 h postchallenge. Anti-mTNF GRM ADCs were dosed at either 10 mg/kg once prior to FITC sensitization. Mice were challenged with adrenocorticotropic hormone (ACTH) 72 h following ADC dosing and plasma was collected 30 min later to assess P1NP level.

In an acute in vivo model of contact hypersensitivity (CHS) mice were sensitized with fluorescein isothiocyanate (FITC) on the abdomen and challenged 6 days later with FITC on the ear,which resulted in an increase in ear swelling that was measured 24 h postchallenge. Anti-mTNF GRM ADCs were dosed at either 3 mg/kg once prior to FITC sensitization. Mice were challenged with adrenocorticotropic hormone (ACTH) 72 h following ADC dosing and plasma was collected 30 min later to assess corticosterone level.

In an acute in vivo model of contact hypersensitivity (CHS) mice were sensitized with fluorescein isothiocyanate (FITC) on the abdomen and challenged 6 days later with FITC on the ear,which resulted in an increase in ear swelling that was measured 24 h postchallenge. Anti-mTNF GRM ADCs were dosed at either 10 mg/kg once prior to FITC sensitization. Mice were challenged with adrenocorticotropic hormone (ACTH) 72 h following ADC dosing and plasma was collected 30 min later to assess corticosterone level.