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TREMFYA® (guselkumab)

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TREMFYA - Immunogenicity in Adult Patients with Plaque Psoriasis or Psoriatic Arthritis

Last Updated: 01/04/2025

SUMMARY

  • In pooled phase 2 and phase 3 clinical trials (VOYAGE 1, VOYAGE 2, and NAVIGATE) that evaluated the efficacy and safety of TREMFYA in adult patients with moderate to severe plaque psoriasis (PsO):
    • Fewer than 6% of patients treated with TREMFYA developed antidrug antibodies (ADA) in up to 52 weeks of treatment.1
    • Of the patients who developed ADA, approximately 7% had antibodies that were classified as neutralizing antibodies.1
    • In pooled phase 3 analyses, approximately 15% of patients treated with TREMFYA developed ADA in up to 264 weeks of treatment.1
    • Of the patients who developed ADA, approximately 5% had antibodies that were classified as neutralizing.1
  • During VOYAGE 1, a phase 3, randomized, double-blind, placebo- and adalimumab comparator-controlled study evaluating the safety and efficacy of TREMFYA in the treatment of patients with moderate to severe plaque PsO, antibodies to guselkumab were detected in 26 of 492 patients (5.3%) through week 44.2
  • During VOYAGE 2, a phase 3, randomized, double-blind, placebo- and adalimumab comparator-controlled study evaluating the safety and efficacy of TREMFYA in the treatment of patients with moderate to severe plaque PsO, antibodies to guselkumab were detected in 57 of 869 patients (6.6%) through week 48.3
  • The VOYAGE 1 and VOYAGE 2 clinical trials assessed the association between ADA development and either clinical response or incidence of injections site reactions (ISRs) through week 264.4,5
  • In pooled phase 3 clinical trials (DISCOVER-1 and DISCOVER-2) that evaluated the efficacy and safety of TREMFYA in adult patients with active psoriatic arthritis (PsA):
    • Up to week 52, 4.5% (n=49) of patients treated with TREMFYA developed ADA. Of these patients, 5 had antibodies that were classified as neutralizing antibodies.1
    • Overall, the small number of patients who were positive for antibodies to guselkumab limits definitive conclusion of the effect of immunogenicity on the pharmacokinetics and efficacy of guselkumab.1
  • In a 24-week integrated safety analysis through the placebo-controlled periods of 2 phase 3, randomized studies of adult patients with active PsA (DISCOVER-1 and DISCOVER-2), 15 patients (2%) (6 patients [1.6%] who received TREMFYA 100 mg every 8 weeks [q8w] and 9 patients [2.4%] who received in the TREMFYA 100 mg every 4 weeks [q4w]) were positive for ADA to guselkumab.6
  • Through 1 year of integrated safety analysis of the DISCOVER-1 and DISCOVER-2 studies, 4.5% (49 of 1094) of patients (14 patients [4.0%] from the placebo group who crossed over to TREMFYA 100 mg q4w, 18 patients [4.8%] who received TREMFYA 100 mg q8w, and 17 patients [4.6%] who received TREMFYA 100 mg q4w) were positive for ADA to guselkumab.7
  • Through week 112 of the DISCOVER-2 study, 53 (7.3%) TREMFYA-treated patients tested positive for antibodies to guselkumab, of these 3 (5.7%) tested positive for neutralizing antibodies.8

COMPANY CORE DATA SHEET

PHARMACOLOGICAL PROPERTIES

Immunogenicity

As with all therapeutic proteins, there is the potential for immunogenicity. The immunogenicity of TREMFYA was evaluated using a sensitive and drug-tolerant immunoassay.1

The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibodies) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of incidence of antibodies to guselkumab with the incidences of antibodies to other products may be misleading.1

Plaque Psoriasis

In pooled phase 2 (X-PLORE) and phase 3 (VOYAGE 1, VOYAGE 2, and NAVIGATE) analyses, fewer than 6% of patients treated with TREMFYA developed ADA in up to 52 weeks of treatment. Of the patients who developed ADA, approximately 7% had antibodies that were classified as neutralizing which equates to 0.4% of all patients treated with TREMFYA. In pooled phase 3 analyses, approximately 15% of patients treated with TREMFYA developed ADA in up to 264 weeks of treatment. Of the patients who developed ADA, approximately 5% had antibodies that were classified as neutralizing which equates to 0.76% of all patients treated with TREMFYA. ADA were not associated with lower efficacy or development of (ISRs).1

Psoriatic Arthritis

In pooled phase 3 (DISCOVER-1 and DISCOVER-2) analyses up to week 52, 4.5% (n=49) of patients treated with TREMFYA developed ADA. Of these patients, 5 had antibodies that were classified as neutralizing antibodies, and 3 developed ISRs through week 52. Overall, the small number of patients who were positive for antibodies to guselkumab limits definitive conclusion of the effect of immunogenicity on the pharmacokinetics and efficacy of guselkumab.1

CLINICAL DATA – MOderate to severe plaque psoriasis

VOYAGE 1

Blauvelt et al (2017)2 evaluated the safety and efficacy of TREMFYA in VOYAGE 1, a phase 3, randomized, double-blind, placebo- and adalimumab comparator-controlled study in patients with moderate to severe plaque PsO.

Study Design/Methods2,9

Abbreviations: DBL, database lock; IGA, Investigator’s Global Assessment; PASI 90, ≥90% improvement in Psoriasis Area and Severity Index score from baseline; q2w, every 2 weeks; q8w, every 8 weeks; R, randomization; SE, secondary endpoint.
aTo maintain blinding, both guselkumab and adalimumab placebos were administered, as necessary.
bProportions of patients achieving an IGA score of cleared/minimal disease (IGA 0/1) and PASI 90 at week 16 in the guselkumab vs placebo group.
cThe last dose of guselkumab was administered at week 252; efficacy was evaluated through week 252.
dSafety was evaluated through week 264.

Results

  • Antibodies to guselkumab were detected in 26 of 492 patients (5.3%) through week 44; titers were generally low (81% ≤1:320).2
  • No association was observed between antibody development and reduced efficacy or ISRs occurrence.2

VOYAGE 2

Reich et al (2017)3 evaluated the safety and efficacy of TREMFYA in VOYAGE 2, a phase 3, multicenter, randomized, double-blind, placebo- and adalimumab comparator-controlled study in patients with moderate to severe plaque PsO.

Study Design/Methods3,10

Abbreviations: DBL, database lock; IGA, Investigator’s Global Assessment; nonres, nonresponders; PASI 90, ≥90% improvement in Psoriasis Area and Severity Index score from baseline; q2w, every 2 weeks; q8w, every 8 weeks; R, randomization; res, responders; SE, secondary endpoint.
aTo maintain blinding, both guselkumab and adalimumab placebos were administered, as necessary.
bAt week 28, guselkumab-treated patients achieving ≥PASI 90 from baseline were randomized in a 1:1 ratio to guselkumab or placebo.
cUpon loss of ≥50% of week-28 PASI 90 response, patients were initiated or retreated with guselkumab.
dPatients with <PASI 90.
ePatients with ≥PASI 90 from baseline at week 28.
fGuselkumab was started at week 28 (5 weeks after the last dose of adalimumab).
gProportions of patients achieving an IGA score of cleared/minimal disease (IGA 0/1) and PASI 90 at week 16 in the guselkumab group.
hDue to inclusion of the randomized withdrawal and retreatment period (weeks 28-76), some patients initiated or were retreated with guselkumab q8w beginning at week 76. Efficacy compared to baseline for guselkumab-treated patient was evaluated starting at week 100 to allow time for adequate response.
iThe last dose of guselkumab was administered at week 252; efficacy was evaluated through week 252.
jSafety was evaluated through week 264.

Results

  • Antibodies to guselkumab were detected in 57 of 869 patients (6.6%) through week 48; titers were generally low (88% ≤1:160).3
  • No apparent associations were observed between antibody development and decreased efficacy or ISRs development.3

Data from Open-Label Extension of VOYAGE 1 and VOYAGE 2

Reich et al (2021)4 and Armstrong et al (2023)5 assessed the association between ADA development and either clinical response or incidence of ISRs through 5 years in the VOYAGE 1 and VOYAGE 2 clinical trials.

Methods

  • ADAs were detected using a validated electrochemiluminescence immunoassay (ECLIA) method, and venous blood samples were collected at regular visits.4
  • Patients treated with at least 1 dose of TREMFYA and who had evaluable serum samples following treatment were assessed for incidence and titers of ADA through week 264.4
  • The proportion of patients achieving clinical response at week 252 and the proportion of patients experiencing ISRs through week 264 were assessed by positive or negative ADA status.4
  • Patients with a positive ADA blood sample at baseline were considered positive if the peak titer of the post TREMFYA treatment samples were ≥2 fold higher than the baseline reference sample.4
  • All TREMFYA-treated patients with positive serum samples for ADAs were further characterized to determine if the developed antibodies could neutralize the biologic activity of guselkumab in vitro.4

Results

  • In VOYAGE 1 and VOYAGE 2, through week 264, 111 of 770 patients (14.4%) and 146 of 943 patients (15.5%) with evaluable serum samples were positive for ADA, respectively.5
  • In VOYAGE 1 and VOYAGE 2, through week 252, 16.1% and 15.8% of patients who continued TREMFYA were positive for ADA, respectively.5
    • Of the patients who discontinued/withdrew TREMFYA before week 252, 7.4% and 14.4% were positive for ADA, respectively.5
  • Peak ADA titers of ≤1:160 were observed in 82.0% and 82.2% of patients in VOYAGE 1 and VOYAGE 2, respectively.4,5
  • Of the TREMFYA-treated patients with positive ADA, 5 (4.5%) in VOYAGE 1 and 8 (5.5%) in VOYAGE 2 were positive for the development of neutralizing antibodies.5
  • Among the 13 patients who tested positive for neutralizing antibodies:
    • All maintained Investigator’s Global Assessment scale (IGA) score 0/1 and/or Psoriasis Area and Severity Index (PASI) 90 responses.4,5
    • At week 252, 8 of 11 patients with evaluable efficacy data achieved clear skin.4,5
  • The proportion of patients who achieved clinical response by ADA status is summarized in Table: Proportion of TREMFYA-Treated Patients with Clinical Response by ADA Status through 5 Years.

Proportion of TREMFYA-Treated Patientsa with Clinical Response by ADA Status through 5 Years4,5
Negativeb
Positivec
Peak Titers for ADA-Positive Patients
10
>10 to <100
≥100 to <1000
≥1000
VOYAGE 1
   TREMFYA-treated patients
   with evaluable samples and
   available efficacy data,a n
536
101
31
43
18
9
   PASI response,d n (%)
      PASI <50%
17 (3.2)
1 (1.0)
0
0
1 (5.6)
0
      PASI ≥50% to <75%
20 (3.7)
3 (3.0)
1 (3.2)
0
2 (11.1)
0
      PASI ≥75% to <90%
54 (10.1)
10 (9.9)
5 (16.1)
4 (9.3)
0
1 (11.1)
      PASI 90
445 (83.0)
87 (86.1)
25 (80.6)
39 (90.7)
15 (83.3)
8 (88.9)
      PASI 100
280 (52.2)
57 (56.4)
19 (61.3)
21 (48.8)
10 (55.6)
7 (77.8)
   IGA score,d n (%)
      IGA 0
292 (54.5)
58 (57.4)
19 (61.3)
22 (51.2)
10 (55.6)
7 (77.8)
      IGA 0/1
437 (81.5)
89 (88.1)
27 (87.1)
39 (90.7)
15 (83.3)
8 (88.9)
      IGA ≥2
99 (18.5)
12 (11.9)
4 (12.9)
4 (9.3)
3 (16.7)
1 (11.1)
VOYAGE 2
   TREMFYA-treated patients
   with evaluable samples and
   available efficacy data,a n
619
117
42
41
27
7
   PASI response,d n (%)
      PASI <50%
22 (3.6)
5 (4.3)
3 (7.1)
2 (4.9)
0
0
      PASI ≥50% to <75%
18 (2.9)
4 (3.4)
0
2 (4.9)
1 (3.7)
1 (14.3)
      PASI ≥75% to <90%
74 (12.0)
14 (12.0)
7 (16.7)
3 (7.3)
4 (14.8)
0
      PASI 90
505 (81.7)
94 (80.3)
32 (76.2)
34 (82.9)
22 (81.5)
6 (85.7)
      PASI 100
323 (52.2)
67 (57.3)
21 (50.0)
24 (58.5)
16 (59.3)
6 (85.7)
   IGA score,d n (%)
      IGA 0e
337 (54.5)
70 (59.8)
22 (52.4)
26 (63.4)
16 (59.3)
6 (85.7)
      IGA 0/1e
527 (85.3)
95 (81.2)
33 (78.6)
32 (78.0)
24 (88.9)
6 (85.7)
      IGA ≥2e
91 (14.7)
22 (18.8)
9 (21.4)
9 (22.0)
3 (11.1)
1 (14.3)
Abbreviations: ADA, antidrug antibody; IGA, Investigator’s Global Assessment; PASI, Psoriasis Area and Severity Index.
aIncludes all patients who received ≥1 dose of TREMFYA, including those who crossed over from placebo or adalimumab. As validated, the sensitivity threshold for ADA to TREMFYA was 15 ng/mL in the presence of up to 3125 ng/mL of guselkumab in human serum samples.
bIncludes all patients whose last sample was negative and excludes patients who were positive for antibodies to TREMFYA through week 264.
cIncludes all patients who had ≥1 positive sample (treatment-boosted or treatment-induced)4 at any time after their first TREMFYA administration through week 264.
dIncludes all patients who had ≥1 evaluable sample after their first TREMFYA administration and for whom efficacy assessments at week 252 were performed.
eIGA results were not available for 1 patient in VOYAGE 2 (N=618).

Proportion of TREMFYA-Treated Patientsa with Immunogenicity Evaluable Serum Samples and ISRs by ADA Status through 5 Years4
VOYAGE 1
VOYAGE 2
Negativeb
Positivec
Negativeb
Positivec
Patients treated with TREMFYA,d n
659
111
797
146
   Patients with ISRs, n (%)
33 (5.0)
9 (8.1)
41 (5.1)
15 (10.3)
Number of TREMFYA injections, n
17,578
3158
20,760
3832
   Injections with ISRs, n (%)
66 (0.4)
18 (0.6)
37 (0.2)
50 (1.3)
Abbreviations: ADA, antidrug antibody; ISR, injection site reaction.
aIncludes all patients who received ≥1 dose of TREMFYA, including those who crossed over from placebo or adalimumab.
bIncludes all patients whose last sample was negative and excludes patients who were positive for antibodies to TREMFYA through week 264.
cIncludes all patients who had ≥1 positive sample at any time after their first TREMFYA administration through week 264.
dIncludes all patients who had ≥1 evaluable sample after their first TREMFYA administration.

clinical data – active PSORIATIC ARTHRITIS

DISCOVER-1 and DISCOVER-2

Rahman et al (2020)6 and Ritchlin et al (2020)7 assessed the safety of TREMFYA in the treatment of adult patients with active PsA using integrated safety results through week 24 and 1 year, respectively, from 2 phase 3, randomized, controlled studies (DISCOVER-1 and DISCOVER-2).

Study Design/Methods

  • In DISCOVER-1, approximately 31% of patients were previously treated with up to 2 antitumor necrosis factor alpha (anti-TNFα) agents whereas in DISCOVER-2, all patients were biologic-naïve.11,12
  • Patients in the studies were randomized 1:1:1 to6:
    • TREMFYA 100 mg at weeks 0 and 4, then q8w (n=375)
    • TREMFYA 100 mg at week 0, then q4w (n=373) or
    • Placebo through week 20, then TREMFYA 100 mg at week 24, then q4w (n=372)
  • Adverse events and clinical laboratory test results were assessed in an integrated safety analysis through week 24 (placebo-controlled phase) in both studies, and in a pooled safety analysis through week 60 in DISCOVER-1 (end of the study) and through week 52 in DISCOVER-2.6,7

Results

  • Through week 24, 15 patients (2%) (6 patients [1.6%] who received TREMFYA 100 mg q8w and 9 patients [2.4%] who received TREMFYA 100 mg q4w) were positive for ADA to guselkumab.6
    • Of the patients who developed ADA, 6.7% (1 of 15) had neutralizing antibodies.
  • Through 1 year, 4.5% (49 of 1094) of patients (14 patients [4.0%] from the placebo group who crossed over to TREMFYA 100 mg q4w, 18 patients [4.8%] who received TREMFYA 100 mg q8w, and 17 patients [4.6%] who received TREMFYA 100 mg q4w) were positive for ADA to guselkumab.7
    • Of the incidence of ADA to guselkumab, 10% were neutralizing antibodies.

DISCOVER-2

McInnes et al (2022)8 evaluated the long-term safety and efficacy of TREMFYA in 739 patients with active PsA through 2 years from the phase 3 DISCOVER-2 study.

  • A total of 727 patients received ≥1 administration of TREMFYA and had available serum samples through week 112.
  • A total of 53 (7.3%) TREMFYA-treated patients tested positive for antibodies to guselkumab, of these 3 (5.7%) tested positive for neutralizing antibodies.
  • Among 22 TREMFYA-treated patients who tested positive for antibodies to guselkumab through week 100 and had American College of Rheumatology (ACR) response evaluations at week 100, 18 (81.8%) achieved ACR20 response and 12 (54.5%) achieved ACR50 response.

LITERATURE SEARCH

A literature search of MEDLINE®, EMBASE®, BIOSIS Previews®, and DERWENT® (and/or other resources, including internal/external databases) was conducted on 27 February 2024.

 

References

Show
1 Data on File. Guselkumab Company Core Data Sheet v15. Janssen Research & Development, LLC. EDMS-ERI-111962822; 2024.  
2 Blauvelt A, Papp KA, Griffiths CEM, et al. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the continuous treatment of patients with moderate to severe psoriasis: Results from the phase III, double-blinded, placebo- and active comparator-controlled VOYAGE 1 trial. J Am Acad Dermatol. 2017;76(3):405-417.  
3 Reich K, Armstrong AW, Foley P, et al. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the treatment of patients with moderate to severe psoriasis with randomized withdrawal and retreatment: Results from the phase III, double-blind, placebo- and active comparator–controlled VOYAGE 2 trial. J Am Acad Dermatol. 2017;76(3):418-431.  
4 Reich K, Armstrong A, Zhu Y, et al. Immunogenicity of guselkumab among patients with moderate-to-severe psoriasis in VOYAGE 1 and VOYAGE 2. presented at: Poster presented at: European Academy of Dermatology and Vernereology; October 13-17, 2021; Berlin, Germany.  
5 Armstrong A, Eyerich K, Conrad C, et al. Immunogenicity and pharmacokinetics of guselkumab among patients with moderate‐to‐severe psoriasis in VOYAGE‐1 and VOYAGE‐2. J Eur Acad Dermatol Venereol. 2023;37(12):e1375-e1379.  
6 Rahman P, Ritchlin C, Helliwell P, et al. Integrated safety results of two phase-3 trials of guselkumab in patients with psoriatic arthritis, through the placebo-controlled periods. Poster presented at: European League Against Rheumatism; June 3-6, 2020; E-Congress.  
7 Ritchlin C, Rahman P, Helliwell P, et al. Pooled safety results from two phase-3 trials of guselkumab in patients with psoriatic arthritis through 1 year. Poster presented at: American College of Rheumatology (ACR); November 5-9, 2020; E-congress.  
8 McInnes IB, Rahman P, Gottlieb AB, et al. Long-term efficacy and safety of guselkumab, a monoclonal antibody specific to the p19 subunit of interleukin-23, through two years: results from a phase 3, randomized, double-blind, placebo-controlled study conducted in biologic-naïve patients with active psoriatic arthritis. Arthritis Rheumatol. 2022;74(3):475-485.  
9 Griffiths CEM, Papp KA, Song M, et al. Maintenance of response through 5 years of continuous guselkumab treatment: results from the phase 3 VOYAGE 1 trial. Poster presented at: Annual Coastal Dermatology Symposium; October 15-16, 2020; E-congress.  
10 Reich K, Armstrong AW, Langley RG, et al. Maintenance of response through up to 5-years of continuous guselkumab treatment of psoriasis in the VOYAGE 2 phase 3 trial. Poster presented at: American Academy of Dermatology; April 23-25, 2021; E-Congress.  
11 Deodhar A, Helliwell P, Boehncke W, et al. Guselkumab in patients with active psoriatic arthritis who were biologic-naive or had previously received TNFα inhibitor treatment (DISCOVER-1): a double-blind, randomised, placebo-controlled phase 3 trial. Lancet. 2020;395(10230):1115-1125.  
12 Mease PJ, Rahman P, Gottlieb AB, et al. Guselkumab in biologic-naive patients with active psoriatic arthritis (DISCOVER-2): a double-blind, randomised, placebo-controlled phase 3 trial. Lancet. 2020;395(10230):1126-1136.