TREMFYA - Effect on Tissue-Resident Memory T Cells

SUMMARY

• The company cannot recommend any practices, procedures, or usage that deviate from the approved labeling.
• ECLIPSE (NCT03090100), a phase 3, multicenter, double-blind, randomized, comparator-controlled trial, evaluated the efficacy of TREMFYA in patients with moderate to severe plaque psoriasis (PsO).^1,2
  • Guselkumab reduced cluster of differentiation (CD)8⁺CD49a⁺CD103⁺ tissue-resident memory T cells (T_RM) at week 24, with the distribution of CD8⁺ T_RM becoming comparable to nonlesional skin.³
• GUIDE (NCT03818035), a phase 3b, randomized, double-blind, parallel-group, multicenter study, evaluated the safety and efficacy of TREMFYA in super responder (SRe) and non-super responder (non-SRe) adult patients with moderate to severe plaque PsO. CD8⁺ T_RM counts were assessed in GUIDE substudies.^4,5,6
  • CD8⁺ T_RM cell counts in lesional skin decreased with guselkumab treatment, reaching levels comparable to nonlesional skin by week 28 in SRes and by week 68 in non-SRes; CD8⁺ T_RM cell suppression was maintained in SRes through weeks 28-68 regardless of dosing interval.⁶
  • CD8⁺ T_RM and interleukin (IL)-17A⁺ T cell counts in lesional skin were reduced by guselkumab up to week 68.⁷
• A prospective cohort study reported reductions in T_RM T cell populations in generalized pustular PsO (GPP) lesions following treatment with guselkumab.⁸

CLINICAL DATA

ECLIPSE

Mehta et al (2021)³ analyzed the immune cell composition of lesional and nonlesional skin samples from a substudy of ECLIPSE, a phase 3, multicenter, double-blind, randomized, comparator-controlled trial evaluating the efficacy of TREMFYA in patients with moderate to severe plaque PsO.

Study Design/Methods

• Patients in the substudy (N=20) were recruited at the Montreal site and were randomized to TREMFYA (n=11) or secukinumab (n=9).
• TREMFYA 100 mg was administered subcutaneously (SC) at weeks 0, 4, and 12, followed by dosing every 8 weeks (Q8W) through week 44.¹
• Skin biopsies were taken from lesional and nonlesional sites.
• The substudy identified the major immune cell types producing IL-23, IL-17A, and tumor necrosis factor alpha (TNF-α) and evaluated modulation of these populations during treatment with guselkumab in the same lesion sampled at baseline before starting treatment.
• Using high-dimensional, unsupervised flow cytometry analysis, mononuclear phagocytes and T cells were examined in the same lesions before and during treatment with guselkumab.

Results

• Among T cell populations, CD8⁺CD49a⁺ and/or CD103⁺ T_RM T cells, CD4⁺CD25⁺FoxP3⁺ Tregs, and CD4⁺CD49a^-CD103^- T cells were increased.
• CD4⁺CD49a^-CD103^- T cells and CD8⁺ memory T cells contributed similarly to IL-17A production.
• CD8⁺CD49a⁺CD103⁺ T_RM decreased at week 24 in guselkumab-treated patients; this difference was also observed when CD8⁺ T_RM subsets were examined as CD49a⁺CD103⁺/⁻ cells. By week 24, the relative distribution of CD8⁺ T_RM was comparable with that of nonlesional skin in the guselkumab-treated group, whereas T_RM proportions remained similar to those in the lesions in the secukinumab-treated group.
• Neither drug modified the frequencies of IL-17A⁺IL-17F⁺/-CD4⁺ or CD8⁺ T cells; the percentages of IL-17A-producing CD4⁺CD49a⁻CD103⁻ T cells and CD8⁺ T_RM clusters at week 24 were not different from those of the lesions.

GUIDE

Eyerich et al (2024)⁶ assessed CD8⁺ T_RM cell counts in substudies of GUIDE, a phase 3b, randomized, double-blind, parallel-group, multicenter study evaluating the safety and efficacy of TREMFYA in SRe and non-SRe adults with moderate to severe plaque PsO.

Study Design/Methods

• In GUIDE part 1 (weeks 0-28), patients received TREMFYA 100 mg SC at weeks 0, 4, 12, and 20. Patients who achieved a Psoriasis Area and Severity Index (PASI) score of 0 at both weeks 20 and 28 were termed SRes.
• In part 2 (weeks 28-68), SRes were randomized to TREMFYA 100 mg SC Q8W or every 16 weeks (Q16W), whereas non-SRes continued open-label TREMFYA Q8W.
• In part 3 (weeks 68-220), SRes with PASI<3 at week 68 discontinued TREMFYA and were followed through week 220, whereas those with PASI≥3 at week 68 or PASI>5 at any visit during parts 2 or 3 received TREMFYA retreatment.

Biomarker Analyses

• Optional exploratory biomarker substudies assessed CD8⁺ T_RM cell counts (CD3⁺, CD8⁺, CD103⁺, and/or CD49a⁺) and serum levels of IL-17A, IL-17F, IL-22, and β defensin (BD)-2 by Q8W/Q16W dosing group and SRe status, using flow cytometry and immunoassay, respectively.
• For CD8⁺ T_RM cell count, skin biopsies were collected from nonlesional skin (at week 0) and lesional skin (at weeks 0, 4, 28, and 68) for fluorescence-activated cell sorting (FACS) analysis.
• For serum cytokine analyses, blood samples were collected at weeks 0, 4, 28, and 68 (and from an independently procured healthy control cohort) and measured using immunoassays.

Results - Biomarker (T_RM-related)

• Compared with nonlesional skin, CD8⁺ T_RM cell counts were elevated in lesional skin at baseline and decreased over time with guselkumab treatment.
• Among SRes, CD8⁺ T_RM cell counts were suppressed from weeks 28 to 68 regardless of dosing interval.
• Reduction of CD8⁺ T_RM cell counts in lesional skin to levels observed in nonlesional skin occurred at week 28 in SRes and at week 68 in non-SRes.

Asadullah et al (2024)⁷ evaluated immunologic differences in skin T cell composition between guselkumab-treated patients with plaque PsO who were classified as SRes and non-SRes, using flow cytometric analyses of nonlesional skin (week 0) and lesional skin (weeks 0, 4, 28, and 68) from 63 patients.

• IL-10⁺ T cell counts were higher at baseline in both nonlesional and lesional skin among SRe vs non-SRe patients (SRe to non-SRe ratio of 3.1:1 and 3.0:1, respectively; P<0.05). This trend was maintained in lesional skin following guselkumab treatment, with significantly higher IL‑10⁺ T‑cell counts in SRes versus non‑SRes at week 4 (SRe:non‑SRe ratio, 4.6:1; P<0.05) and week 28 (4.4:1; P<0.05).
• Treg-cell (CD4⁺CD25⁺FoxP3⁺) counts were higher in SRes at weeks 4 and 28 (SRe to non-SRe ratio of 3.1:1 and 2.9:1, respectively; P<0.05).
• Guselkumab reduced lesional CD8⁺ T_RM and IL-17A⁺ T cell counts through week 68. Normalization of these populations to levels observed in nonlesional skin appeared to occur earlier in SRes (week 28) than in non-SRes (week 68).

Prospective Cohort Study

Lu et al (2024)⁸ evaluated T_RM cell populations in GPP lesional skin before and after treatment with guselkumab in a prospective single-center observational cohort study conducted in China.

Study Design/Methods

• Patients with GPP received guselkumab 100 mg SC at weeks 0 and 4, and Q8W thereafter. All patients also applied emollients and received oral acitretin 20 mg daily.
• Skin biopsies from 6 patients with GPP (pre- and post-treatment) were compared with 6 normal control skin samples.
• Multiplex immunofluorescence was used to evaluate changes in T_RM cells before and after guselkumab treatment.

Results

• GPP lesions exhibited higher levels of CD8⁺CD69⁺CD103⁺ and CD4⁺CD69⁺CD103⁺ T_RM cells compared with normal controls, indicating increased T_RM cell accumulation in GPP skin lesions.
• CD8⁺ T_RM cell counts were elevated in both the dermis and epidermis of GPP lesions versus normal controls before treatment.
• Following guselkumab treatment, proportions of CD4⁺ and CD8⁺ T_RM cells in skin lesions decreased.

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, Derwent Drug File (and other resources, including internal/external databases) was conducted on 27 May 2026.