TREMFYA®
(guselkumab)
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TREMFYA® (guselkumab)
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TREMFYA - Treatment of Crohn’s Disease with Subcutaneous Induction (GRAVITI Study)
Last Updated: 03/26/2025
SUMMARY
- The company cannot recommend any practices, procedures, or usage that deviate from the approved labeling.
- GRAVITI (NCT05197049) is a phase 3, treat-through clinical trial in adult patients with moderately to severely active Crohn’s disease (CD) that evaluates the efficacy and safety of subcutaneous (SC) induction with TREMFYA. Efficacy and safety results are summarized below.
CLINICAL DATA
Phase 3 Subcutaneous Induction Study in Crohn's Disease - GRAVITI
Panaccione et al (2023)1
Study Design/Methods
- GRAVITI is a phase 3, randomized, double-blind, placebo (PBO)-controlled, parallel-group, multicenter, treat-through study.
- Enrolled patients had a history of inadequate response or intolerance to oral corticosteroids (CSs), azathioprine (AZA), 6-mercaptopurine (6-MP), methotrexate (MTX), or biologics (BIO-IR).
- A total of 347 patients were randomized 1:1:1 to:
- TREMFYA 400 mg SC at weeks 0, 4, and 8 followed by 200 mg SC every 4 weeks (q4w; N=115)
- TREMFYA 400 mg SC at weeks 0, 4, and 8 followed by 100 mg SC every 8 weeks (q8w; N=115)
- PBO (N=117)
- Patients who met rescue criteria received rescue treatment at week 16: PBO patients switched to TREMFYA, and TREMFYA patients stayed on TREMFYA per treat-through design (sham rescue).
- The coprimary endpoints were clinical remission at week 12 (Crohn’s Disease Activity Index [CDAI] <150) and endoscopic response at week 12 (≥50% improvement from baseline in the Simple Endoscopic Score for Crohn's Disease [SES-CD]).
- Other multiplicity-controlled endpoints were clinical remission at week 24, patient-reported outcome-2 (PRO-2) remission at week 12, clinical response at week 12, clinical remission at week 48, and endoscopic response at week 48.
- All endpoints assessed through week 12 compared the combined TREMFYA 400 mg SC treatment arm to PBO. Assessments after week 12 compared each TREMFYA SC maintenance regimen to PBO.
- All patients who met rescue criteria were considered not to have met efficacy endpoints after week 16.
- Safety was assessed through week 48.
Results
Patient Characteristics
- Baseline characteristics were similar across groups:
- Mean age: 37.5 years
- Mean CD disease duration: 8 years
- Mean CDAI: 296.9
- Mean SES-CD: 12.0
- BIO-IR: 46.4%
Efficacy
- The coprimary and all multiplicity-controlled endpoints were met. TREMFYA 400 mg SC induction demonstrated superiority to PBO at week 12.
- Both TREMFYA SC maintenance dosage regimens were also superior to PBO at weeks 24 and 48.
- Additionally, in prespecified analyses of subpopulations defined by prior biologic history, greater proportions of TREMFYA-treated patients achieved the endpoints compared to those treated with PBO.
- For the coprimary and other multiplicity controlled endpoints through week 48, see Table: Summary of Coprimary and Multiplicity-Controlled Endpoints through Week 48.
| Endpoints | TREMFYA Combined 400 mg SC q4w (N=230) | TREMFYA 400 mg SC q4w → TREMFYA 100 mg SC q8w (N=115) | TREMFYA 400 mg SC q4w → TREMFYA 200 mg SC q4w (N=115) | Placebo SC (N=117) |
|---|---|---|---|---|
| Clinical remissiona (Coprimary endpoint) | 56.1% | - | - | 21.4% |
| Treatment difference vs placebo | 34.9% P<0.001 | - | - | - |
| Endoscopic responseb (Coprimary endpoint) | 41.3% | - | - | 21.4% |
| Treatment difference vs placebo | 19.9% P<0.001 | - | - | - |
| PRO-2 remissionc | 49.1% | - | - | 17.1% |
| Treatment difference vs placebo | 32.1% P<0.001 | - | - | - |
| Clinical responsed | 73.5% | - | - | 33.3% |
| Treatment difference vs placebo | 40.3% P<0.001 | - | - | - |
| Clinical remission at week 24 | - | 60.9% | 58.3% | 21.4% |
| Treatment difference vs placebo | - | 39.3% P<0.001 | 37% P<0.001 | - |
| Clinical remission at week 48 | - | 60% | 66.1% | 17.1% |
| Treatment difference vs placebo | - | 42.8% P<0.001 | 48.9% P<0.001 | - |
| Endoscopic response at week 48 | - | 44.3% | 51.3% | 6.8% |
| Treatment difference vs placebo | - | 37.5% P<0.001 | 44.6% P<0.001 | - |
| Abbreviations: BIO, biologic ; CD, Crohn’s disease; CDAI, Crohn’s Disease Activity Index; COVID-19, coronavirus disease 2019; PRO-2, patient-reported outcome-2; q4w/q8w, every 4 or 8 weeks; SC, subcutaneous; SES-CD, Simple Endoscopic Score for Crohn's Disease. aClinical remission: CDAI score <150. bEndoscopic response: ≥50% improvement from baseline in SES-CD score. cPRO-2 remission: Abdominal pain average daily score ≤1 and stool frequency average daily score ≤3, and no worsening of abdominal pain or stool frequency from baseline. dClinical response: ≥100-point reduction from baseline in CDAI score or CDAI score <150. Note: Participants who had a CD-related surgery (with the exception of minor procedures such as drainage of a superficial abscess or seton placement, etc), a prohibited change in CD medication, discontinued study intervention for any reason (other than COVID-19 related reasons [excluding COVID-19 infection] or regional crisis), or met rescue criteria (only applicable after week 16) were considered not to have met the endpoint at the designated timepoint. Participants who discontinued study intervention due to COVID-19 related reasons (excluding COVID-19 infection) or regional crisis had their observed data used, if available. After accounting for the aforementioned data handling rules, participants who were missing data pertaining to an endpoint at a designated timepoint were considered not to have achieved the endpoint. The adjusted treatment difference(s), and P-value(s) were based on the common risk difference by use of Mantel-Haenszel stratum weights and the Sato variance estimator. The stratification factors are baseline CDAI score (≤300 or >300), baseline SES-CD score (≤12 or >12), and BIO-failure status at baseline (yes or no). | ||||
Safety
- Key safety event rates per 100 patient years through week 48 were similar among treatment groups, see Table: Safety through Week 48.
| Placebo SCa | TREMFYA 400 mg SC q4w → TREMFYA 100 mg SC q8w | TREMFYA 400 mg SC q4w → TREMFYA 200 mg SC q4w | All TREMFYAb | |
|---|---|---|---|---|
| Safety analysis set, N | 117 | 115 | 115 | 274 |
| Average duration of follow-up, weeks | 30.0 | 47.0 | 48.0 | 44.8 |
| Average exposure, number of administrations | 7.1 | 6.8 | 11.8 | 8.5 |
| Total PYs of follow-up, years | 67.3 | 103.5 | 105.7 | 235.0 |
| Deathsc, n (%) | 0 | 1 (0.9) | 0 | 1 (0.4) |
| Participants with 1 or more | ||||
| AEs, n (%) | 77 (65.8) | 95 (82.6) | 92 (80.0) | 220 (80.3) |
| Events per 100 PYs follow-up | 413.0 | 307.2 | 327.2 | 312.8 |
| SAEs, n (%) | 16 (13.7) | 15 (13.0) | 9 (7.8) | 25 (9.1) |
| Events per 100 PYs follow-up | 37.1 | 15.5 | 13.2 | 13.2 |
| AEs leading to DC of study agent, n (%) | 10 (8.5) | 4 (3.5) | 3 (2.6) | 8 (2.9) |
| Events per 100 PYs follow-up | 14.9 | 6.8 | 2.8 | 4.7 |
| Serious infectionsd, n (%) | 0 | 2 (1.7) | 1 (0.9) | 4 (1.5) |
| AEs of special interest, n (%) | ||||
| Active tuberculosis | 0 | 0 | 0 | 0 |
| Malignanciese | 0 | 1 (0.9) | 0 | 1 (0.4) |
| Abbreviations: AE, adverse event; DC, discontinuation; MedDRA, Medical Dictionary for Regulatory Activities; PY, participant-years; q4w/q8w, every 4 or 8 weeks; SAE, serious adverse event; SC, subcutaneous. aIncludes all placebo participants excluding data after a participant is rescued with TREMFYA. bIncludes all participants initially randomized to TREMFYA at week 0, and placebo participants who were rescued with TREMFYA; only data after a participant crossed over to TREMFYA is included. cFatal gunshot wound (nonsuicidal). dInfections were defined as any AE which was coded to the MedDRA system organ class “Infections and infestations.” eBasal cell carcinoma of skin; participant continued in the study. Note: Participants are counted only once for any given event under specific column, regardless of the number of times they actually experienced the event. | ||||
Subgroup Analyses
Corticosteroid Use and Corticosteroid Outcomes at Week 482
- Among all patients receiving oral CS at baseline, a greater proportion of patients receiving TREMFYA than that of patients receiving PBO was not receiving CS at week 48. For more details, see Table: Corticosteroid Use at Week 48: Primary Analysis Population.
| TREMFYA 400 mg SC q4w → TREMFYA 100 mg SC q8w | TREMFYA 400 mg SC q4w → TREMFYA 200 mg SC q4w | Placebo | |
|---|---|---|---|
| Full analysis set, N | 115 | 115 | 117 |
| Patients receiving oral CS (prednisone or budesonide)a at baseline, n/N (%) | 32/115 (27.8) | 38/115 (33.0) | 33/117 (28.2) |
| Patients not receiving oral CS at week 48 among patients receiving oral CS at baseline, n/N (%) | 20/32 (62.5) | 31/38 (81.6) | 6/33 (18.2) |
| Adjusted treatment difference (95% CI)b | 41.7 (18.4-65.1) | 62.9 (42.3-83.4) | - |
| Patients not receiving oral CS for at least 90 days prior to week 48 among patients receiving oral CS at baseline, n/N (%) | 19/32 (59.4) | 31/38 (81.6) | 6/33 (18.2) |
| Adjusted treatment difference (95% CI)b | 38.8 (15.6-61.9) | 62.9 (42.3-83.4) | |
| Abbreviations: CD, Crohn’s disease; CDAI, Crohn’s Disease Activity Index; CI, confidence interval; COVID-19, coronavirus disease 2019; CS, corticosteroid; q4w/q8w, every 4 or 8 weeks; SC, subcutaneous; SES-CD, Simple Endoscopic Score for Crohn’s Disease. aNo patients were receiving beclomethasone at baseline. bThe adjusted treatment difference(s) and CI(s) were based on the common risk difference by use of Mantel-Haenszel stratum weights and the Sato variance estimator. The stratification factors were the baseline CDAI score (≤300 or >300), baseline SES-CD (≤12 or >12), and baseline biologic-failure status (yes or no). Note: All participants in all treatment groups (TREMFYA and placebo) who met the rescue criteria were considered not to have met the efficacy endpoints after week 16. Participants who had a CD-related surgery or a prohibited change in concomitant CD medications or for whom the study agent was discontinued due to a lack of efficacy, an adverse event of worsening CD, COVID-19 infection, or for reasons other than a lack of efficacy or an adverse event of worsening CD (excluding COVID-19-related reasons or regional crisis) before the designated analysis timepoint were considered not to have achieved the binary endpoint from that timepoint onward. Participants for whom the study agent was discontinued due to COVID-19-related reasons (excluding COVID-19 infection) or regional crisis had their observed data used, if available, to determine the responder status from that timepoint onward. | |||
- Clinical remission at week 48:
- TREMFYA 100 mg SC q8w (N=115): 60.0% (adjusted treatment difference vs PBO Δ42.8% [31.6-54.0])
- TREMFYA 200 mg SC q4w (N=115): 66.1% (adjusted treatment difference vs PBO Δ48.9% [37.9-59.9])
- PBO group (N=117): 17.1%
- CS-free clinical remission at week 48:
- TREMFYA 100 mg SC q8w (N=115): 59.1% (adjusted treatment difference vs PBO Δ42.8% [31.6-53.9])
- TREMFYA 200 mg SC q4w (N=115): 66.1% (adjusted treatment difference vs PBO Δ49.8% [38.9-60.7])
- PBO group (N=117): 16.2%
- 90-day CS-free clinical remission at week 48:
- TREMFYA 100 mg SC q8w (N=115): 58.3% (adjusted treatment difference vs PBO Δ41.9% [30.7-53.1])
- TREMFYA 200 mg SC q4w (N=115): 65.2% (adjusted treatment difference vs PBO Δ49.0% [38.0-59.9])
- PBO group (N=117): 16.2%
Efficacy by Baseline Disease Characteristics3
- Predefined subgroup analyses were conducted based on the following:
- Disease duration: ≤5, >5 to ≤15, and >15 years
- Disease location assessed by central reader: ileum, colon, and both
- CDAI score: ≤300 and >300
- C-reactive protein (CRP): ≤5 and >5 mg/L
- Fecal calprotectin (FCP): ≤250 and >250 µg/g
- SES-CD: ≤12 and >12
- Clinical remission and endoscopic response at week 12 were achieved by a greater proportion of patients treated with TREMFYA than that of patients treated with PBO across all subgroups. For more details, see Table: Clinical Remission at Week 12 by Baseline Disease Characteristics.
| TREMFYA 400 mg SC n (%) | Placebo n (%) | Rate Difference (95% CI) | |
|---|---|---|---|
| All patients | 230 (56.1) | 117 (21.4) | 34.9 (25.1-44.6) |
| CD duration (years) | |||
| ≤5 | 103 (52.4) | 67 (22.4) | 31.5 (17.2-45.9) |
| >5 to ≤15 | 91 (62.6) | 31 (22.6) | 37.9 (20.0-55.8) |
| >15 | 36 (50.0) | 19 (15.8) | 27.2 (1.5-52.9) |
| Involved disease location (based on central reader assessment) | |||
| Ileum only | 52 (55.8) | 22 (27.3) | 29.2 (4.7-53.6) |
| Colon only | 81 (55.6) | 40 (17.5) | 37.2 (20.9-53.5) |
| Ileum and colon | 97 (56.7) | 55 (21.8) | 34.2 (19.4-49.1) |
| CDAI score | |||
| ≤300 | 137 (66.4) | 68 (26.5) | 39.9 (26.9-53.0) |
| >300 | 93 (40.9) | 49 (14.3) | 26.3 (12.2-40.5) |
| CRP (mg/L) | |||
| ≤5 | 110 (52.7) | 47 (27.7) | 24.7 (8.5-40.8) |
| >5 | 120 (59.2) | 70 (17.1) | 42.8 (30.5-55.1) |
| Fecal calprotectin (μg/g) | |||
| ≤250 | 67 (59.7) | 31 (25.8) | 34.1 (13.3-54.8) |
| >250 | 162 (54.3) | 86 (19.8) | 35.3 (24.1-46.4) |
| SES-CD | |||
| ≤12 | 140 (52.1) | 72 (23.6) | 28.2 (15.2-41.2) |
| >12 | 90 (62.2) | 45 (17.8) | 45.3 (31.4-59.2) |
| Abbreviations: BIO, biologic; CD, Crohn’s disease; CDAI, Crohn’s Disease Activity Index; CI, confidence interval; COVID-19, coronavirus disease 2019; CRP, C-reactive protein; SC, subcutaneous; SES-CD, Simple Endoscopic Score for Crohn’s Disease. Note: Participants who had a CD-related surgery (with the exception of minor procedures, such as drainage of a superficial abscess or seton placement) or a prohibited change in CD medication or for whom the study intervention was discontinued for any reason (other than COVID-19 related reasons [excluding COVID-19 infection] or regional crisis) were considered not to have met the endpoint at the designated timepoint. Participants who were discontinued from the study intervention due to COVID-19-related reasons (excluding COVID-19 infection) or regional crisis had their observed data used, if available. After accounting for the aforementioned data handling rules, participants who were missing data pertaining to an endpoint at a designated timepoint were considered not to have achieved the endpoint. The adjusted treatment difference(s) and CI(s) were based on the common risk difference by use of Mantel-Haenszel stratum weights and the Sato variance estimator. The stratification factors were the baseline CDAI score (≤300 or >300), baseline SES-CD (≤12 or >12), and baseline BIO-failure status (yes or no). | |||
- For endoscopic response at week 12, see Table: Endoscopic Response at Week 12 by Baseline Disease Characteristics.
| TREMFYA 400 mg SC n (%) | Placebo n (%) | Rate Difference (95% CI) | |
|---|---|---|---|
| All patients | 230 (41.3) | 117 (21.4) | 19.9 (10.2 to 29.6) |
| CD duration (years) | |||
| ≤5 | 103 (43.7) | 67 (28.4) | 16.6 (2.0 to 31.2) |
| >5 to ≤15 | 91 (42.9) | 31 (9.7) | 29.8 (14.4 to 45.2) |
| >15 | 36 (30.6) | 19 (15.8) | 9.9 (-16.0 to 35.8) |
| Involved disease location (based on central reader assessment) | |||
| Ileum only | 52 (26.9) | 22 (4.5) | 23.0 (8.6 to 37.3) |
| Colon only | 81 (43.2) | 40 (17.5) | 25.4 (8.9 to 42.0) |
| Ileum and colon | 97 (47.4) | 55 (30.9) | 15.0 (-0.9 to 30.8) |
| CDAI score | |||
| ≤300 | 137 (43.8) | 68 (26.5) | 18.1 (4.8 to 31.4) |
| >300 | 93 (37.6) | 49 (14.3) | 22.4 (8.5 to 36.4) |
| CRP (mg/L) | |||
| ≤5 | 110 (43.6) | 47 (27.7) | 16.0 (0.5 to 31.4) |
| >5 | 120 (39.2) | 70 (17.1) | 20.3 (7.9 to 32.7) |
| Fecal calprotectin (μg/g) | |||
| ≤250 | 67 (43.3) | 31 (29.0) | 14.0 (-7.4 to 35.5) |
| >250 | 162 (40.1) | 86 (18.6) | 20.9 (10.1 to 31.8) |
| SES-CD | |||
| ≤12 | 140 (35.0) | 72 (20.8) | 14.0 (1.7 to 26.3) |
| >12 | 90 (51.1) | 45 (22.2) | 29.1 (13.6 to 44.6) |
| Abbreviations: BIO, biologic; CD, Crohn’s disease; CDAI, Crohn’s Disease Activity Index; CI, confidence interval; COVID-19, coronavirus disease 2019; CRP, C-reactive protein; SC, subcutaneous; SES-CD, Simple Endoscopic Score for Crohn’s Disease. Note: Participants who had a CD-related surgery (with the exception of minor procedures, such as drainage of a superficial abscess or seton placement) or a prohibited change in CD medication or for whom the study intervention was discontinued for any reason (other than COVID-19-related reasons [excluding COVID-19 infection] or regional crisis) were considered not to have met the endpoint at the designated timepoint. Participants for whom the study intervention was discontinued due to COVID-19-related reasons (excluding COVID-19 infection) or regional crisis had their observed data used, if available. After accounting for the aforementioned data handling rules, participants who were missing data pertaining to an endpoint at a designated timepoint were considered not to have achieved the endpoint. The adjusted treatment difference(s) and CI(s) were based on the common risk difference by use of Mantel-Haenszel stratum weights and the Sato variance estimator. The stratification factors were the baseline CDAI score (≤300 or >300), baseline SES-CD (≤12 or >12), and baseline BIO-failure status (yes or no). | |||
Efficacy by Baseline Disease Demographics4
Study Design/Methods
- Predefined subgroup analyses were conducted based on the following:
- Gender: male and female
- Race: White, non-White, Black or African American, Asian, other, and not reported/missing
- Ethnicity: Hispanic or Latino, not Hispanic or Latino, and not reported/missing
- Median age in years: ≤36, >36, <65, and ≥65
- Weight in kg by quartile: <57.5, ≥57.5 to <68.5, ≥68.5 to <80.5, and ≥80.5
- Disease duration: ≤5, >5 to ≤15, and >15 years
- Concomitant CD-related medications: receiving or not receiving 5-aminosalicylic acid (5-ASA) compounds, oral CSs, and AZA/6-MP/MTX as discrete categories
Results
- Clinical remission and endoscopic response at week 12 were achieved by a greater proportion of patients treated with TREMFYA than that of patients treated with PBO across all subgroups. For more details, see Table: Clinical Remission at Week 12 by Baseline Disease Charac
teristics.
| TREMFYA 400 mg SC n (%) | Placebo n (%) | Rate Difference (95% CI) | |
|---|---|---|---|
| All patients | 230 (56.1) | 117 (21.4) | 34.9 (25.1-44.6) |
| Sex | |||
| Male | 136 (58.1) | 67 (25.4) | 33.4 (20.3-46.6) |
| Female | 94 (53.2) | 50 (16.0) | 37.3 (22.5-52.1) |
| Race | |||
| White | 158 (57.0) | 71 (25.4) | 32.3 (19.7-44.9) |
| Non-White | 52 (48.1) | 33 (12.1) | 38.0 (17.5-58.4) |
| Black or African American | 4 (100.0) | 5 (0.0) | NE |
| Asian | 48 (43.8) | 28 (14.3) | 32.8 (10.5-55.0) |
| Others | 0 | 0 | NE |
| Not reported or missing | 20 (70.0) | 13 (23.1) | 53.7 (25.3-82.1) |
| Ethnicity | |||
| Hispanic or Latino | 18 (66.7) | 9 (22.2) | NE |
| Not Hispanic or Latino | 192 (53.6) | 93 (22.6) | 30.8 (19.8-41.8) |
| Not reported or missing | 20 (70.0) | 15 (13.3) | 57.7 (31.5-83.9) |
| Age (years) | |||
| ≤36 (median) | 116 (60.3) | 63 (19.0) | 39.8 (26.8-52.8) |
| >36 (median) | 114 (51.8) | 54 (24.1) | 27.9 (13.2-42.5) |
| <65 | 224 (56.3) | 114 (21.9) | 34.3 (24.4-44.2) |
| ≥65 | 6 (50.0) | 3 (0.0) | NE |
| Weight (kg) | |||
| <57.5 | 56 (46.4) | 30 (10.0) | 29.5 (12.3-46.8) |
| ≥57.5 to <68.5 | 51 (62.7) | 36 (22.2) | 42.7 (24.4-61.0) |
| ≥68.5 to <80.5 | 56 (55.4) | 31 (25.8) | 35.0 (15.7-54.3) |
| ≥80.5 | 67 (59.7) | 20 (30.0) | 34.2 (9.4-59.1) |
| CD duration (years) | |||
| ≤5 | 103 (52.4) | 67 (22.4) | 31.5 (17.2-45.9) |
| >5 to ≤15 | 91 (62.6) | 31 (22.6) | 37.9 (20.0-55.8) |
| >15 | 36 (50.0) | 19 (15.8) | 27.2 (1.5-52.9) |
| Oral 5-ASA compounds | |||
| Receiving | 91 (51.6) | 50 (18.0) | 33.4 (17.7-49.1) |
| Not receiving | 139 (59.0) | 67 (23.9) | 36.7 (24.0-49.5) |
| Oral CS (including budesonide and beclomethasone dipropionate) | |||
| Receiving | 70 (62.9) | 33 (21.2) | 42.7 (23.9-61.5) |
| Not receiving | 160 (53.1) | 84 (21.4) | 32.7 (21.2-44.1) |
| 6-MP/AZA/MTX | |||
| Receiving | 66 (59.1) | 33 (30.3) | 29.8 (11.7-47.9) |
| Not receiving | 164 (54.9) | 84 (17.9) | 37.3 (26.0-48.6) |
| Abbreviations: 5-ASA, 5-aminosalicylic acid; 6-MP, 6-mercaptopurine; AZA, azathioprine; CD, Crohn’s disease; CDAI, Crohn’s Disease Activity Index; CI, confidence interval; COVID-19, coronavirus disease 2019; CS, corticosteroid; MTX, methotrexate; NE, not estimable; SC, subcutaneous; SES-CD, Simple Endoscopic Score for Crohn’s Disease. Note: Participants who had a CD-related surgery (with the exception of minor procedures, such as drainage of a superficial abscess or seton placement) or a prohibited change in CD medication or for whom the study intervention was discontinued for any reason (other than COVID-19-related reasons [excluding COVID-19 infection] or regional crisis) were considered not to have met the endpoint at the designated timepoint. Participants for whom the study intervention was discontinued due to COVID-19-related reasons (excluding COVID-19 infection) or regional crisis had their observed data used, if available. After accounting for the aforementioned data handling rules, participants who were missing data pertaining to an endpoint at a designated timepoint were considered not to have achieved the endpoint. The adjusted treatment difference(s) and CI(s) were based on the common risk difference by use of Mantel-Haenszel stratum weights and the Sato variance estimator. The stratification factors were the baseline CDAI score (≤300 or >300), baseline SES-CD (≤12 or >12), and baseline BIO-failure status (yes or no). Subgroup analyses were not evaluated (ie, rate difference, 95% CI, and P-value were not calculated) whenever there were less than 10 participants in at least 1 treatment group. | |||
- For endoscopic response at week 12, see Table: Endoscopic Response at Week 12 by Baseline Disease Characteristics.
| TREMFYA 400 mg SC n (%) | Placebo n (%) | Rate Difference (95% CI) | |
|---|---|---|---|
| All patients | 230 (41.3) | 117 (21.4) | 19.9 (10.2 to 29.6) |
| Sex | |||
| Male | 136 (40.4) | 67 (22.4) | 16.7 (3.9 to 29.5) |
| Female | 94 (42.6) | 50 (20.0) | 22.9 (8.3 to 37.6) |
| Race | |||
| White | 158 (39.9) | 71 (21.1) | 21.0 (8.8 to 33.3) |
| Non-White | 52 (40.4) | 33 (21.2) | 16.2 (-4.8 to 37.1) |
| Black or African American | 4 (50.0) | 5 (20.0) | NE |
| Asian | 48 (39.6) | 28 (21.4) | 16.0 (-6.0 to 38.0) |
| Others | 0 | 0 | NE |
| Not reported or missing | 20 (55.0) | 13 (23.1) | 29.3 (-5.2 to 63.7) |
| Ethnicity | |||
| Hispanic or Latino | 18 (16.7) | 9 (11.1) | NE |
| Not Hispanic or Latino | 192 (42.2) | 93 (22.6) | 19.7 (8.8 to 30.7) |
| Not reported or missing | 20 (55.0) | 15 (20.0) | 25.7 (-4.8 to 56.3) |
| Age (years) | |||
| ≤36 (median) | 116 (44.0) | 63 (17.5) | 26.1 (13.0 to 39.1) |
| >36 (median) | 114 (38.6) | 54 (25.9) | 11.5 (-3.0 to 26.0) |
| <65 | 224 (41.1) | 114 (21.9) | 19.3 (9.5 to 29.2) |
| ≥65 | 6 (50.0) | 3 (0.0) | NE |
| Weight (kg) | |||
| <57.5 | 56 (42.9) | 30 (20.0) | 19.2 (-1.5 to 40.0) |
| ≥57.5 to <68.5 | 51 (43.1) | 36 (22.2) | 24.7 (5.1 to 44.3) |
| ≥68.5 to <80.5 | 56 (42.9) | 31 (19.4) | 28.8 (8.7 to 48.9) |
| ≥80.5 | 67 (37.3) | 20 (25.0) | 20.6 (1.6 to 39.6) |
| CD duration (years) | |||
| ≤5 | 103 (43.7) | 67 (28.4) | 16.6 (2.0 to 31.2) |
| >5 to ≤15 | 91 (42.9) | 31 (9.7) | 29.8 (14.4 to 45.2) |
| >15 | 36 (30.6) | 19 (15.8) | 9.9 (-16.0 to 35.8) |
| Oral 5-ASA compounds | |||
| Receiving | 91 (42.9) | 50 (20.0) | 20.8 (5.2 to 36.4) |
| Not receiving | 139 (40.3) | 67 (22.4) | 18.8 (6.2 to 31.5) |
| Oral CS (including budesonide and beclomethasone dipropionate) | |||
| Receiving | 70 (44.3) | 33 (15.2) | 26.1 (8.1 to 44.2) |
| Not receiving | 160 (40.0) | 84 (23.8) | 17.0 (5.0 to 29.0) |
| 6-MP/AZA/MTX | |||
| Receiving | 66 (45.5) | 33 (15.2) | 27.6 (10.0 to 45.2) |
| Not receiving | 164 (39.6) | 84 (23.8) | 16.9 (5.4 to 28.5) |
| Abbreviations: 5-ASA, 5-aminosalicylic acid; 6-MP, 6-mercaptopurine; AZA, azathioprine; CD, Crohn’s disease; CDAI, Crohn’s Disease Activity Index; CI, confidence interval; COVID-19, coronavirus disease 2019; CS, corticosteroid; MTX, methotrexate; NE, not estimable; SC, subcutaneous; SES-CD, Simple Endoscopic Score for Crohn’s Disease. Note: Participants who had a CD-related surgery (with the exception of minor procedures, such as drainage of a superficial abscess or seton placement) or a prohibited change in CD medication or for whom the study intervention was discontinued for any reason (other than COVID-19-related reasons [excluding COVID-19 infection] or regional crisis) were considered not to have met the endpoint at the designated timepoint. Participants for whom the study intervention was discontinued due to COVID-19-related reasons (excluding COVID-19 infection) or regional crisis had their observed data used, if available. After accounting for the aforementioned data handling rules, participants who were missing data pertaining to an endpoint at a designated timepoint were considered not to have achieved the endpoint. The adjusted treatment difference(s), CI(s), and P-value(s) were based on the common risk difference by use of Mantel-Haenszel stratum weights and the Sato variance estimator. The stratification factors were the baseline CDAI score (≤300 or >300), baseline SES-CD (≤12 or >12), and baseline BIO-failure status (yes or no). Subgroup analyses were not evaluated (ie, rate difference, 95% CI, and P-value were not calculated) whenever there were less than 10 participants in at least 1 treatment group. | |||
Health-related Quality of Life
Sands et al (2025)5
- PROMIS-29 consists of the following 7 domains as well as a pain intensity item: 5 symptom domains (anxiety, depression, fatigue, sleep disturbance, and pain interference) and 2 functional domains (physical function and social participation).
- Physical component summary (PCS) and mental component summary (MCS) scores were calculated on the basis of domain T-scores.
- Clinically meaningful improvement (CMI) was defined using predefined thresholds for each domain and for the PCS and MCS scores.
- Higher scores indicated better health outcomes for the functional domains and the PCS and MCS scores but worse symptoms for the symptom domains and pain intensity (rated on a 0-10 scale).
Results
- Baseline mean PROMIS-29 domain scores were similar across the treatment groups in functional domain scores, symptom domain scores and pain intensity scores with all values indicating impaired HRQoL.
- At weeks 12 and 48, compared with patients receiving PBO, patients treated with TREMFYA showed a greater improvement in each domain T-score, the pain intensity numeric rating scale (NRS) score, and the PCS and MCS scores. For more details, see Table: Change from Baseline at Weeks 12 and 48 in PROMIS-29 Score.
- At weeks 12 and 48, greater percentage of patients treated with TREMFYA compared to PBO achieved CMI in each domain, the pain intensity NRS score, and the PCS and MCS scores, see Figure: CMI in Each PROMIS-29 Domain, Pain Intensity, PCS and MCS Scores at Weeks 12 and 48.
| TREMFYA 400 mg SC q4w → TREMFYA 100 mg SC q8w (N=115) | TREMFYA 400 mg SC q4w → TREMFYA 200 mg SC q4w (N=115) | Placebo (N=117) | |
|---|---|---|---|
| Anxiety T-score, mean (SD)a,b | |||
| Baseline | 58.26 (9.660) N=107 | 59.42 (9.674) N=109 | 59.33 (10.342) N=112 |
| Week 12 | - | - | -2.79 (9.116) N=111 |
| Week 48 | -5.00 (8.008) N=104 | -6.42 (10.496) N=101 | -2.30 (5.668) N=109 |
| Depression T-score, mean (SD)a,b | |||
| Baseline | 56.76 (9.293) N=107 | 56.07 (9.698) N=109 | 56.83 (10.254) N=112 |
| Week 12 | - | - | -2.03 (8.158) N=111 |
| Week 48 | -4.53 (7.940) N=104 | -4.98 (9.763) N=101 | -1.92 (5.549) N=109 |
| Fatigue T-score, mean (SD)a,b | |||
| Baseline | 58.00 (8.961) N=107 | 60.78 (8.147) N=109 | 58.54 (9.384) N=112 |
| Week 12 | - | - | -2.95 (7.513) N=111 |
| Week 48 | -6.40 (8.383) N=104 | -9.65 (11.065) N=101 | -2.02 (5.557) N=109 |
| Pain interference T-score, mean (SD)a,b | |||
| Baseline | 59.65 (8.197) N=107 | 62.09 (6.480) N=109 | 61.00 (6.986) N=112 |
| Week 12 | - | - | -3.45 (7.492) N=111 |
| Week 48 | -7.81 (9.064) N=104 | -9.31 (9.894) N=101 | -2.00 (5.645) N=109 |
| Pain intensity NRS, mean (SD)a,b | |||
| Baseline | 5.6 (2.30) N=107 | 5.8 (1.84) N=109 | 5.7 (2.16) N=112 |
| Week 12 | - | - | -0.9 (1.94) N=111 |
| Week 48 | -2.4 (3.11) N=104 | -2.7 (2.64) N=101 | -0.5 (1.81) N=109 |
| Physical function T-score, mean (SD)a,b | |||
| Baseline | 45.72 (8.488) N=107 | 43.43 (8.182) N=109 | 45.60 (8.969) N=112 |
| Week 12 | - | - | 2.12 (7.882) N=111 |
| Week 48 | 4.59 (7.188) N=104 | 6.40 (8.640) N=101 | 1.04 (4.784) N=109 |
| Sleep disturbance T-score, mean (SD)a,b | |||
| Baseline | 54.44 (7.692) N=107 | 55.25 (6.691) N=109 | 54.65 (7.259) N=112 |
| Week 12 | - | - | -1.48 (6.955) N=111 |
| Week 48 | -2.75 (6.522) N=104 | -5.27 (7.692) N=101 | -1.19 (4.868) N=109 |
| Social participation T-score, mean (SD)a,b | |||
| Baseline | 47.58 (9.166) N=107 | 44.80 (8.143) N=109 | 46.80 (8.741) N=112 |
| Week 12 | - | - | 2.23 (7.446) N=111 |
| Week 48 | 5.88 (8.474) N=104 | 8.61 (9.519) N=101 | 1.87 (6.190) N=109 |
| PROMIS-29 summary T-scores | |||
| PCS score, mean (SD)a,b | |||
| Baseline | 44.85 (8.732) N=107 | 42.36 (8.205) N=109 | 44.56 (8.929) N=112 |
| Week 12 | - | - | 2.46 (7.723) N=111 |
| Week 48 | 5.54 (7.569) N=104 | 7.60 (9.102) N=101 | 1.32 (5.083) N=109 |
| MCS score, mean (SD)a,b | |||
| Baseline | 42.29 (8.327) N=107 | 40.22 (7.301) N=109 | 41.58 (8.432) N=112 |
| Week 12 | - | - | 2.96 (6.778) N=111 |
| Week 48 | 6.64 (7.599) N=104 | 9.27 (9.904) N=101 | 2.19 (5.505) N=109 |
| Abbreviations: AE, adverse event; CD, Crohn’s disease; CDAI, Crohn’s Disease Activity Index; COVID-19, coronavirus disease 2019; MCS, Mental Component Summary; MMRM, Mixed Model Repeated Measures; NRS, numeric rating scale; PCS, Physical Component Summary; PROMIS-29, Patient-Reported Outcomes Measurement Information System 29; q4w/q8w, every 4 or 8 weeks; SC, subcutaneous; SD, standard deviation; SES-CD, Simple Endoscopic Score for Crohn’s Disease. aParticipants who had a CD-related surgery or a prohibited change in concomitant CD medication; who met rescue criteria (only applicable after week 16); or for whom the study agent was discontinued due to a lack of efficacy, an AE of worsening CD, or for any other reason other than COVID-19-related reasons or regional crisis prior to the analysis timepoint had their baseline value carried forward. Participants for whom the study agent was discontinued due to COVID-19-related reasons (excluding COVID-19 infection) or regional crisis had their observed data used, if available. bParticipants who had insufficient data for calculating the PROMIS-29 domain score at the designated analysis timepoint did not have their missing data imputed. Note: All endpoints assessed through week 12 were compared between the combined TREMFYA 400 mg SC treatment arm and placebo arm; assessments after week 12 were compared between each TREMFYA SC maintenance regimen and placebo. The P-value for comparison of each TREMFYA treatment group with the placebo group was based on an MMRM analysis, with change from baseline in the PROMIS-29 domain score as the response and the treatment group, visit, baseline PROMIS-29 domain score, BIO-failure status (yes or no), baseline CDAI stratification (≤300 or >300), baseline SES-CD (≤12 or >12), and interaction term of visit with the treatment group and interaction term of visit with the baseline PROMIS-29 domain score as the explanatory variables. | |||
Participants who had a CD-related surgery, a prohibited change in concomitant CD medication, met rescue criteria (only applicable after wk 16) or discontinued the study agent due to lack of efficacy, an AE of worsening CD, or for any other reason other than COVID-19-related reasons or regional crisis prior to the analysis timepoint were considered not to have achieved the binary endpoint from that timepoint onwards. Participants who had discontinued the study agent due to COVID-19-related reasons (excluding COVID-19 infection) or a regional crisis had their observed data used, if available, to determine responder status from that timepoint onwards.
Note: CMI was according to previously defined thresholds for each domain and the MCS and PCS (pain intensity ≥3; anxiety, depression, sleep disturbance, and physical function ≥5; fatigue, social participation, PCS, and MCS ≥7; pain interference ≥9). The CIs for the proportion of subjects meeting the endpoint in each treatment group were based on the normal approximation confidence limits. The treatment differences (Δ) and CIs were based on the common risk difference by use of Mantel-Haenszel stratum weights and the Sato variance estimator. The stratification factors are baseline CDAI score (≤300 or >300), baseline SES-CD score (≤12 or >12), and BIO-failure status at baseline (yes or no).
Abbreviations: AE, adverse event; BIO, biologic; CD, Crohn’s disease; CDAI, Crohn’s Disease Activity Index; CI, Confidence Interval; CMI, clinically meaningful improvement; GUS, guselkumab; MCS, Mental Component Summary; PBO, placebo; PCS, Physical Component Summary; PROMIS-29, Patient-Reported Outcomes Measurement Information System 29; SC, subcutaneous; SES-CD, Simple Endoscopic Score for Crohn’s Disease; Wk, Week.
Richards et al (2025)6
Study Design/Methods
- Using a 92-analyte inflammatory protein panel, serum proteins were analyzed at weeks 0 and 12 in patients randomized to receive TREMFYA 400 mg SC q4w or PBO in the GRAVITI trial (n=290) and a subset of patients randomized to TREMFYA 200 mg IV q4w or PBO in the GALAXI trials (n=292).
- In the GRAVITI trial, transcriptional profiling from each of the 5 anatomic segments was performed at weeks 0 and 12 in 277 patients using RNA sequencing.
- Segmental molecular inflammation was assessed using the tissue inflammation score (bMIS), which is correlated with segmental histology scores (ie, GHAS), endoscopic scores, and subscores defined by SES-CD.
- Treatment effect was analyzed using molecularly inflamed samples (bMIS >0) from segments with SES-CD >0 at baseline, and transcriptional gene modules were assessed for differential expression.
Results
- Serum protein changes at week 12 with TREMFYA 400 mg SC q4w induction were highly correlated with those seen with TREMFYA 200 mg IV q4w induction (R=0.96; P<0.05). Similar reductions were observed with interferon gamma, interleukin (IL)-17A, CRP, and FCP (P<0.05).
- For tissue, segmental molecular inflammation assessed by bMIS was correlated with segmental histological and endoscopic subscores.
- At week 12, TREMFYA SC induction reduced key cellular and inflammatory transcriptional modules across all anatomic segments, including plasma cell, inflammatory epithelial, neutrophil, and IL-23/T helper 17 (Th17) biology.
- Reduction in molecular inflammation across the 5 anatomic segments corresponded to segmental endoscopic improvement observed in isolated ileal, ileocolonic, and colonic patient subgroups.
- For anti-inflammatory effect of TREMFYA IV and SC induction at week 12, see Figure: TREMFYA IV and SC Induction Show Similar Anti-inflammatory Effects in Serum at Week 12.
Abbreviations: ADA, adenosine deaminase; CCL11, C-C motif chemokine ligand 11; CCL20, Cchemokine (C-C motif) ligand 20; CDCP1, CUB domain containing protein 1; CSF-1, colony-stimulating factor-1; CXCL1, C-X-C motif chemokine ligand 1; CXCL9, chemokine (C-X-C motif) ligand 9; CXCL11, C-X-C motif chemokine 11; DNER, delta/Notch-like epidermal growth factor-related receptor; HGF, hepatocyte growth factor; IL, interleukin; MCP-3, monocyte chemotactic protein-3; MMP10, matrix metallopeptidase 10; OSM, oncostatin M; SCF, stem cell factor; SLAMF1, signaling lymphocytic activation molecule; TGF-alpha, transforming growth factor alpha; TNFB, tumor necrosis factor beta; TNFSF14, tumor necrosis factor ligand superfamily member 14; VEGFA, vascular endothelial growth factor A.
Pooled Analyses
Danese et al (2025)7
Study Design/Methods
- Safety events were defined as the proportion of patients with ≥1 adverse event (AE) during the induction period (weeks 0-12).
Results
- Serious infections were reported in 1 patient each in the TREMFYA IV and SC groups but did not result in treatment discontinuation. No serious infections were reported in patients receiving PBO in either group.
- During the induction period in GRAVITI, 6 (0.4%) of 1376 TREMFYA SC injections were associated with injection-site reactions (ISRs), including pruritus, erythema, and swelling. ISRs beyond the induction period with TREMFYA SC remained low (≤1%) and were comparable regardless of induction administration route.
- During the induction period, no cases of active TB, anaphylaxis, serum sickness reactions, MACE, or VTE were reported.
- One opportunistic infection (esophageal candidiasis) was reported in patients receiving PBO in both the IV and SC induction groups, whereas 2 opportunistic infections (cytomegalovirus infection and esophageal candidiasis) were reported in the TREMFYA IV induction group and none in the TREMFYA SC induction group.
- One malignancy (basal cell carcinoma), which did not result in discontinuation, was reported in a patient in the TREMFYA 400 mg SC group.
- During the induction period, 1 death (attributed to a nonsuicidal [not self-inflicted] gunshot wound) was reported in a patient treated with TREMFYA SC.
- During the induction period, clinically significant hepatic disorders were reported in 2 patients in the TREMFYA 200 mg IV group (1 serious adverse event and 1 AE leading to discontinuation) and 1 patient in the TREMFYA 400 mg SC group (1 AE leading to discontinuation).
- All cases of hepatic disorders were confounded by additional diagnoses or concomitant medications.
- For details on safety events, see Table: Patients with ≥1 Safety Events During the Induction Period (Weeks 0-12).
| IV Induction | SC Induction | |||
|---|---|---|---|---|
| TREMFYA 200 mg IV | Placebo | TREMFYA 400 mg SC | Placebo | |
| Analysis set, n | 649 | 211 | 230 | 117 |
| AEs, n (%) | 304 (46.8) | 109 (51.7) | 107 (46.5) | 58 (49.6) |
| SAEs, n (%) | 19 (2.9) | 13 (6.2) | 5 (2.2) | 9 (7.7) |
| AEs leading to discontinuation, n (%) | 11 (1.7) | 9 (4.3) | 1 (0.4) | 3 (2.6) |
| Serious infections, n (%) | 1 (0.2) | 0 | 1 (0.4) | 0 |
| Malignanciesa, n (%) | 0 | 0 | 1 (0.4) | 0 |
| Opportunistic infectionsb, n (%) | 2 (0.3) | 1 (0.5) | 0 | 1 (0.9) |
| Clinically important hepatic disordersc, n (%) | 2 (0.3) | 0 | 1 (0.4) | 0 |
| Abbreviations: AE, adverse event; HLT, high level term; IV, intravenous; MedDRA, Medical Dictionary for Regulatory Activities; SAE, serious adverse event; SC, subcutaneous; SMQ, standardized MedDRA query. aMalignancies were defined as the narrow terms in the MedDRA SMQ of “Malignant Tumours.” Nonmelanoma skin cancers were identified by the MedDRA HLT of “Skin neoplasms malignant and unspecified (excl melanoma).” bOpportunistic infections were defined as the narrow terms in the MedDRA SMQ of “Opportunistic Infections.” cClinically important hepatic disorders were defined as hepatic disorder AEs reported as SAEs or AEs leading to discontinuation of the study intervention. Note: Patients were counted only once for any given event, regardless of the number of times they actually experienced the event. AEs were coded using MedDRA version 26.0. | ||||
Literature Search
A literature search of MEDLINE®
References
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