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TREMFYA® (guselkumab)

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Concomitant Use With Methotrexate and Other Conventional Synthetic DMARDs

Last Updated: 02/06/2025

Summary

  • The company cannot recommend any practices, procedures, or usage that deviate from the approved labeling.
  • A pooled analysis from DISCOVER-1 and DISCOVER-2 reported the efficacy and safety of TREMFYA in patients with active psoriatic arthritis (PsA) through 52 weeks with or without concomitant conventional synthetic disease-modifying antirheumatic drug (csDMARD) use at baseline.1
  • A post hoc analysis of DISCOVER-2 reported the efficacy of TREMFYA in inducing long-term (week 100) disease control in patients with or without concomitant nonbiologic disease-modifying antirheumatic drug (nbDMARD) use at baseline across specific PsA disease domains.2
  • Another post hoc analysis of DISCOVER-2 reported the potential predictors of TREMFYA efficacy results in patients with or without concomitant csDMARD use at baseline across specific PsA disease domains through week 100.3
  • A post hoc analysis of the COSMOS study reported efficacy results in patients with concomitant baseline use of methotrexate (MTX) or any nonbiologic csDMARD at weeks 24 and 48.4
  • A pooled safety analysis of a phase 2 study and phase 3 studies (DISCOVER-1, DISCOVER-2, and COSMOS) reported the incidence of adverse events (AEs) per 100 patient-years (PY) with and without MTX use. Grade 1 elevations in hepatic transaminases (aspartate aminotransferase [AST]/alanine aminotransferase [ALT]) in patients with or without baseline use of MTX were also reported.5
  • A pooled safety analysis reported elevated levels of serum ALT, serum AST, and blood bilirubin in patients receiving TREMFYA with or without baseline use of MTX through 1 year from DISCOVER-1, 2 years from DISCOVER-2, and 1 year from a phase 2 study.6

CLINICAL DATA

Post Hoc Analyses

Ritchlin et al (2022)1 evaluated the efficacy and safety of TREMFYA in pooled data from 2 randomized, double-blind, placebo-controlled, multicenter, phase 3 studies (DISCOVER-1 and DISCOVER-2) in patients with active PsA.

Study Design/Methods

DISCOVER-1 Study Design7,8

A screenshot of a computer screen Description automatically generated

Abbreviations: CASPAR, Classification Criteria for Psoriatic Arthritis; CRP, C-reactive protein; DMARD, disease-modifying antirheumatic drug; EE, early escape; NSAID, nonsteroidal anti-inflammatory drug; PsA, psoriatic arthritis; PsO, psoriasis; q4w, every 4 weeks; q8w, every 8 weeks; R, randomized; SC, subcutaneously; TNFi, tumor necrosis factor inhibitor.
a114 patients in the placebo group crossed over to TREMFYA q4w; 12 patients received placebo only before study drug discontinuation.
bPatients were eligible to initiate/increase background medications if there was <5% improvement from baseline in tender and swollen joint counts at week 16.

DISCOVER-2 Study Design9,10

A screenshot of a computer screen Description automatically generated

Abbreviations: CASPAR, Classification Criteria for Psoriatic Arthritis; CRP, C-reactive protein; DMARD, disease-modifying antirheumatic drug; EE, early escape; NSAID, nonsteroidal anti-inflammatory drug; PsA, psoriatic arthritis; PsO, psoriasis; q4w, every 4 weeks; q8w, every 8 weeks; R, randomized; SC, subcutaneously.
a114 patients in the placebo group crossed over to TREMFYA q4w; 12 patients received placebo only before study drug discontinuation.
bPatients were eligible to initiate/increase background medications if there was <5% improvement from baseline in tender and swollen joint counts at week 16.

Results

Efficacy

Proportion of Patients Achieving Efficacy Responses With and Without csDMARD Use at Weeks 24 and 52 Among Pooled DISCOVER-1 and DISCOVER-2 Patients1,11
csDMARD Use
Week 24
Week 52
Odds Ratioa (95% CI)
TREMFYA 100 mg
PBO (n=109)
TREMFYA 100 mg
PBO (n=229)
TREMFYA 100 mg vs PBO
q4w (n=232)
q8w (n=225)
q4w (n=267)
q8w (n=261)
q4w
q8w
ACR20 responseb, n (%)
   No
   csDMARD
80
(66)
76
(62)
27
(23)
97
(80)
89
(73)
74
(63)
6.6
(3.7-11.6)
5.6
(3.2-9.8)
   Any
   csDMARD
152
(60)
149
(59)
82
(32)
170
(68)
172
(68)
155
(61)
3.2
(2.2-4.6)
3.0
(2.1-4.3)
      MTX
137
(63)
120
(57)
73
(32)
149
(68)
143
(68)
138
(61)
3.6
(2.4-5.3)
2.8
(1.9-4.2)
TREMFYA 100 mg
PBO (n=46)
TREMFYA 100 mg
PBO (n=139)
TREMFYA 100 mg vs PBO
q4w
(n=127)
q8w
(n=116)
q4w
(n=181)
q8w
(n=169)
q4w
q8w
ACR50 responseb, n (%)
   No
   csDMARD
43
(36)
44
(36)
12
(10)
64
(53)
62
(51)
37
(31)
4.9
(2.4-9.8)
5.0
(2.5-10.1)
   Any
   csDMARD
84
(33)
72
(28)
34
(13)
117
(46)
107
(42)
102
(40)
3.2
(2.1-5.1)
2.6
(1.6-4.0)
      MTX
76
(35)
56
(27)
31
(14)
104
(48)
83
(40)
91
(40)
3.4
(2.1-5.4)
2.3
1.4-3.8)
TREMFYA 100 mg
PBO (n=17)
TREMFYA 100 mg
PBO
(n=64)
TREMFYA 100 mg vs PBO
q4w
(n=58)
q8w
(n=61)
q4w
(n=101)
q8w
(n=102)
q4w
q8w
ACR70 responseb, n (%)
   No
   csDMARD
25
(21)
25
(20)
3
(2)
36
(30)
41
(34)
18
(15)
10.0
(2.9-34.1)
9.9
(2.9-33.7)
   Any
   csDMARD
33
(13)
36
(14)
14
(6)
65
(26)
61
(24)
46
(18)
2.6
(1.3-5.0)
2.8
(1.5-5.4)
      MTX
30
(14)
30
(14)
11
(5)
59
(27)
47
(22)
38
(17)
3.1
(1.5-6.4)
3.3
(1.6-6.8)

TREMFYA 100 mg
PBO (n=47)
TREMFYA 100 mg
PBO (n=198)
TREMFYA 100 mg vs PBO
q4w
(n=193)
q8w
(n=171)
q4w
(n=219)
q8w
(n=183)
q4w
q8w
IGA 0/1 responsec, n (%)
   No
   csDMARD
75
(84)
68
(72)
17
(20)
77
(86)
72
(77)
67
(80)
21.1
(9.7-46.1)
10.3
(5.1-20.7)
   Any
   csDMARD
118
(64)
103
(63)
30
(17)
142
(77)
111
(68)
131
(74)
8.8
(5.3-14.4)
8.3
(5.0-13.7)
      MTX
107
(66)
88
(64)
29
(18)
125
(78)
94
(68)
120
(74)
9.2
(5.5-15.4)
8.1
(4.8-13.8)
TREMFYA 100 mg
PBO (n=20)
TREMFYA 100 mg
PBO (n=158)
TREMFYA 100 mg vs PBO
q4w
(n=141)
q8w
(n=119)
q4w
(n=174)
q8w
(n=142)
q4w
q8w
IGA 0 responsed, n (%)
   No
   csDMARD
54
(61)
42
(45)
6
(7)
59
(66)
57
(61)
56
(67)
20.1
(7.9-51.0)
10.5
(4.2-26.5)
   Any
   csDMARD
87
(47)
77
(47)
14
(8)
115
(62)
85
(52)
102
(58)
10.4
(5.6-19.4)
10.3
(5.5-19.3)
      MTX
77
(48)
65
(47)
13
(8)
101
(63)
69
(50)
93
(57)
10.6
(5.5-20.2)
10.3
(5.3-19.8)
TREMFYA 100 mg
PBO (n=156)
TREMFYA 100 mg
PBO (n=223)
TREMFYA 100 mg vs PBO
q4w
(n=227)
q8w
(n=218)
q4w
(n=236)
q8w
(n=233)
q4w
q8w
FACIT-F responsee, n (%)
   No
   csDMARD
75
(62)
72
(59)
38
(32)
72
(60)
73
(60)
64
(54)
3.4
(2.0-5.8)
3.0
(1.8-5.1)
   Any
   csDMARD
152
(60)
146
(58)
118
(46)
164
(65)
160
(63)
159
(63)
1.8
(1.2-2.5)
1.6
(1.1-2.2)
      MTX
135
(62)
121
(58)
108
(48)
147
(67)
130
(62)
146
(64)
1.8
(1.2-2.6)
1.5
(1.0-2.2)
TREMFYA 100 mg
PBO (n=106)
TREMFYA 100 mg
PBO (n=162)
TREMFYA 100 mg vs PBO
q4w
(n=191)
q8w
(n=171)
q4w
(n=208)
q8w
(n=189)
q4w
q8w
HAQ-DI responsef, n (%)
   No
   csDMARD
56
(55)
50
(46)
16
(14)
63
(62)
60
(56)
43
(39)
7.3
(3.8-14.1)
5.1
(2.6-9.7)
   Any
   csDMARD
135
(57)
121
(52)
90
(38)
145
(61)
129
(56)
119
(50)
2.1
(1.5-3.1)
1.8
(1.2-2.6)
      MTX
120
(58)
93
(48)
82
(39)
127
(62)
105
(54)
107
(51)
2.2
(1.5-3.2)
1.4
(1.0-2.2)
TREMFYA 100 mg
PBO (n=33)
TREMFYA 100 mg
PBO (n=137)
TREMFYA 100 mg vs PBO
q4w
(n=104)
q8w
(n=113)
q4w
(n=169)
q8w
(n=157)
q4w
q8w
PASDAS LDA responseg, n (%)
   No
   csDMARD
39
(32)
42
(34)
12
(10)
65
(54)
62
(51)
47
(40)
4.2
(2.1-8.5)
4.6
(2.3-9.4)
   Any
   csDMARD
65
(26)
71
(28)
21
(8)
104
(41)
95
(38)
90
(35)
3.9
(2.3-6.5)
4.3
(2.6-7.3)
      MTX
60
(28)
54
(26)
18
(8)
94
(43)
78
(37)
79
(35)
4.4
(2.5-7.8)
4.0
(2.3-7.2)
TREMFYA 100 mg
PBO
(n=29)
TREMFYA 100 mg
PBO
(n=105)
TREMFYA 100 mg vs PBO
q4w
(n=85)
q8w
(n=91)
q4w
(n=134)
q8w
(n=115)
q4w
q8w
MDA responseh, n (%)
   No
   csDMARD
30
(25)
35
(29)
9
(8)
56
(46)
44
(36)
34
(29)
4.0
(1.8-8.8)
4.9
(2.2-10.7)
   Any
   csDMARD
55
(22)
56
(22)
20
(8)
78
(31)
71
(28)
71
(28)
3.3
(1.9-5.6)
3.3
(1.9-5.7)
      MTX
52
(24)
44
(21)
17
(8)
69
(32)
55
(26)
62
(27)
3.9
(2.2-6.9)
3.3
(1.8-6.0)
Abbreviations: ACR20, ≥20% improvement in the American College of Rheumatology criteria; ACR50, ≥50% improvement in the American College of Rheumatology criteria; ACR70, ≥70% improvement in the American College of Rheumatology criteria; BSA, body surface area; CI, confidence interval; CRP, C-reactive protein; csDMARD, conventional synthetic disease-modifying antirheumatic drug; FACIT-F, Functional Assessment of Chronic Illness Therapy-Fatigue; HAQ-DI, Health Assessment Questionnaire-Disability Index; IGA, Investigator’s Global Assessment; MDA, minimal disease activity; MTX, methotrexate; PASDAS LDA, Psoriatic Arthritis Disease Activity Score Low Disease Activity; PBO, placebo; q4w, every 4 weeks; q8w, every 8 weeks.
aWeek 24 response rates are compared between TREMFYA and PBO via odds ratio and 95% CIs.
b≥20%, ≥50%, and ≥70%, respectively, improvement from baseline in both tender joint count (68 joints) and swollen joint count (66 joints) and ≥20%, ≥50%, and ≥70%, respectively, improvement from baseline in at least 3 of the 5 assessments: patient’s assessment of pain, patient’s global assessment of disease activity, physician’s global assessment of disease activity, HAQ-DI, and CRP.
cIGA psoriasis score of 0 (cleared) or 1 (minimal) and ≥2-grade reduction from baseline in the IGA psoriasis score among patients with ≥3% BSA with psoriasis and IGA ≥2 at baseline.
dIGA psoriasis score of 0 and ≥2-grade reduction from baseline in the IGA psoriasis score among patients with ≥3% BSA with psoriasis and IGA ≥2 at baseline.
e≥4-point improvement in the FACIT-F score from baseline. The FACIT-F score is calculated based on the FACIT-F questionnaire that comprises 13 questions, with each question graded on a 5-point scale (0-4). The FACIT-F scores can range from 0 to 52, with higher scores indicating less fatigue.
f≥0.35-point improvement in the HAQ-DI score from baseline among patients with a HAQ-DI score ≥0.35 at baseline. The score is the average of the computed categories scores (dressing, arising, eating, walking, hygiene, gripping, and daily living). Lower scores indicate better functioning.
gPASDAS score ≤3.2. The PASDAS score is calculated from a combination of the tender and swollen joint counts, Physical Component Summary Short Form-36 score, physician’s global assessment of disease activity, patient’s global assessment of disease activity (arthritis and psoriasis), enthesitis, dactylitis count, and CRP.
h5/7 MDA criteria were met (tender joint count ≤1, swollen joint count ≤1, psoriasis activity and severity index ≤1, patient’s assessment of pain ≤15, patient’s global assessment of disease activity ≤20, HAQ-DI score ≤0.5, and tender entheseal points ≤1).

Proportion of Patients Achieving Joint, Skin, and Disease State Response With and Without csDMARD Use from Weeks 24-52 Among Pooled DISCOVER-1 and DISCOVER-2 Patients1
csDMARD Use
ACR20, %
ACR50, %
ACR70, %
IGA 0/1, %
IGA 0, %
MDA, %
TREMFYA 100 mg
TREMFYA 100 mg
TREMFYA 100 mg
TREMFYA 100 mg
TREMFYA 100 mg
TREMFYA 100 mg
q4w
q8w
q4w
q8w
q4w
q8w
q4w
q8w
q4w
q8w
q4w
q8w
None
80.2c
73.0c
52.9d
50.8c
29.8b
33.6c
86.5a
76.6a
66.3c
60.6d
46.3e
36.1c
Any
67.5b
68.0b
46.4c
42.3c
25.8c
24.1b
77.2c
67.7a
62.5d
51.8a
31.0c
28.1c
   MTX
68.3b
68.4c
47.7c
39.7c
27.1c
22.5b
77.6c
68.1a
62.7c
50.0a
31.7c
26.3c
Abbreviations: ACR20, ≥20% improvement in the American College of Rheumatology criteria; ACR50, ≥50% improvement in the American College of Rheumatology criteria; ACR70, ≥70% improvement in the American College of Rheumatology criteria; csDMARD, conventional synthetic disease-modifying antirheumatic drug; IGA, Investigator’s Global Assessment; MDA, minimal disease activity; MTX, methotrexate; q4w, every 4 weeks; q8w, every 8 weeks.
a% change, 0 to <5.
b% change, 5 to <10
c% change, 10 to <15.
d% change, 15 to <20.
e% change, 20 to <25.
Safety
  • No additional safety signals were reported with TREMFYA from weeks 24 to 52.

Ritchlin et al (2022)2 conducted a post hoc analysis of DISCOVER-2 that evaluated the efficacy of TREMFYA (N=493; q4w, n=245; q8w, n=248) in inducing long-term (week 100) disease control from the Group for Research and Assessment for Psoriasis and Psoriatic Arthritis (GRAPPA)-recommended domains across specific baseline subgroups.

Results


Proportion of Patients Achieving Efficacy Responses With and Without nbDMARD and MTX Use at Week 100 Among DISCOVER-2 Patients2,a
ACR50,
n (%)
ACR70,
n (%)
IGA 0,
n (%)
Dactylitis Resolution,
n (%)
Enthesitis Resolution,
n (%)
MDAb,
n (%)
TREMFYA 100 mg
TREMFYA 100 mg
TREMFYA 100 mg
TREMFYA 100 mg
TREMFYA 100 mg
TREMFYA 100 mg
q4w
q8w
q4w
q8w
q4w
q8w
q4w
q8w
q4w
q8w
q4w
q8w
Baseline concomitant nbDMARD use
   Yes
89
(52)
85
(50)
56
(33)
53
(31)
76
(58)
60
(52)
66
(71)
66
(84)
79
(65)
76
(67)
61
(36)
61
(36)
   No
48
(64)
51
(65)
29
(39)
35
(45)
38
(72)
37
(62)
21
(75)
26
(81)
26
(53)
34
(76)
33
(44)
39
(50)
Baseline concomitant MTX use
   Yes
83
(57)
69
(49)
52
(36)
43
(30)
67
(59)
50
(52)
57
(70)
51
(81)
71
(68)
65
(69)
55
(38)
50
(36)
   No
54
(54)
67
(63)
33
(33)
45
(42)
47
(67)
47
(59)
30
(77)
41
(85)
34
(52)
45
(70)
39
(39)
50
(47)
Abbreviations: ACR50, ≥50% improvement in the American College of Rheumatology criteria; ACR70, ≥70% improvement in the American College of Rheumatology criteria; HAQ, Health Assessment Questionnaire; IGA, Investigator’s Global Assessment; MDA, minimal disease activity; MTX, methotrexate; nbDMARD, nonbiologic disease-modifying antirheumatic drug; q4w, every 4 weeks; q8w, every 8 weeks.
aThe response rates at week 100 were determined using the nonresponder imputation for data missing due to patient discontinuation.
b≥5/7 MDA criteria were met (tender joint count ≤1, swollen joint count ≤1, psoriasis activity and severity index ≤1, patient pain visual analog scale ≤15, patient global disease activity visual analog scale ≤20 [arthritis and psoriasis], HAQ score ≤0.5, and/or tender entheseal points ≤1).

McInnes et al (2022)3 conducted a post hoc analysis of DISCOVER-2 that assessed potential predictors of TREMFYA (N=442) efficacy results by baseline patient subgroups across specific PsA disease domains through week 100.

Results

  • At baseline, csDMARD and MTX use was observed in 69% and 60% of patients (n=739; TREMFYA 100 mg q4w, 69% and 60%; TREMFYA 100 mg q8w, 68% and 57%; placebo, 70% and 63%), respectively.
  • No consistent significant baseline predictors of long-term TREMFYA efficacy were observed across the PsA disease domains assessed.
  • Least square mean (LSM) changes in various clinical outcomes are presented in Table: LSM Changes in Clinical Outcomes from Baseline to Week 100 Among DISCOVER-2 Patients.

LSM Changes in Clinical Outcomes from Baseline to Week 100 Among DISCOVER-2 Patients3
csDMARD Use
LSM Change in Scoresa
DAPSA
Scoreb
PASDAS
Score
PASI
Scorec
Spinal
Paind
LEI
Scoree
DSSe
Yes
-33.6
(n=301)
-3.5
(n=298)
-16.6
(n=226)
-2.9
(n=107)
-2.0
(n=207)
-6.9
(n=153)
No
-35.8
(n=141)
-3.9
(n=138)
-18.4
(n=108)
-2.6
(n=21)
-1.8
(n=86)
-8.5
(n=53)
Abbreviations: BSA, body surface area; csDMARD, conventional synthetic disease-modifying antirheumatic drug; DAPSA, Disease Activity Index for Psoriatic Arthritis; DSS, Dactylitis Severity Score; IGA, Investigator’s Global Assessment; LEI, Leeds Enthesitis Index; LSM, least square mean; PASDAS, Psoriatic Arthritis Disease Activity Score; PASI, Psoriasis Area and Severity Index; PsO, psoriasis.
aThe LSM change was derived from a multivariate linear model adjusting for baseline subgroups.
bDAPSA score: remission, 0-4; low, 5-14; moderate, 15-28; high, >28.
cThePASI score (0-72) among patients with baseline IGA ≥2 and ≥3% BSA with PsO.
dSpinal pain (visual analog scale, 0-10 cm) among patients with imaging-confirmed sacroiliitis.
eTheLEI score (0-6) among patients with enthesitis and an available LEI score/DSS at baseline.

McInnes et al (2022)4 conducted a post hoc analysis of a phase 3b, randomized, double-blind (COSMOS) study in patients with PsA who had an inadequate response (IR) to a tumor necrosis factor inhibitor (TNFi) to evaluate the efficacy of TREMFYA in maintaining response across disease domains through 1 year in various subgroups of TNFi-IR patients with PsA.

Study Design/Methods

  • Adult patients with active PsA (according to the ClASsification criteria for Psoriatic ARthritis [CASPAR]; ≥3 swollen joints and ≥3 tender joints), active (≥1 psoriatic plaque of ≥2 cm) or a documented history of plaque psoriasis (PsO) or current nail PsO, and who had shown a lack of benefit or intolerance to 1-2 TNFi were included.12
  • At week 0, patients were randomized 2:1 to receive12:
    • TREMFYA 100 mg subcutaneously (SC) at weeks 0 and 4 and then q8w through week 44
    • Placebo at weeks 0, 4, 12, and 20, followed by TREMFYA 100 mg at weeks 24, 28, 36, and 44
  • The efficacy endpoints in patients with concomitant use of MTX or any nonbiologic csDMARD at weeks 24 and 48 were evaluated.

Results


Proportion of Patients Achieving ACR20 and ACR50 at Weeks 24 and 48 Based on Concomitant MTX or Other csDMARD Use4
csDMARD Use
n/N (%)
ACR20
ACR50
Week 24
Week 48
Week 24
Week 48
PBO
TREMFYA 100 mg
q8w
TREMFYA 100 mg
q8w
PBO
TREMFYA 100 mg
q8w
TREMFYA 100 mg
q8w
MTX
15/50 (30)
56/105 (53)
66/105 (63)
3/50 (6)
20/105 (19)
42/105 (40)
Others
9/36 (25)
33/69 (48)
37/69 (54)
5/36 (14)
18/69 (26)
27/69 (39)
Abbreviations: ACR20, ≥20% improvement in the American College of Rheumatology criteria; ACR50, ≥50% improvement in the American College of Rheumatology criteria; csDMARD, conventional synthetic disease-modifying antirheumatic drug; MTX, methotrexate; PBO, placebo; q8w, every 8 weeks.

Proportion of Patients Achieving PASI 90, PASI 100, and MDA at Weeks 24 and 48 Based on Concomitant MTX or Other csDMARD Use4
csDMARD Use
n/N (%)
PASI 90a
PASI 100a
MDA
Week 24
Week 48
Week 24
Week 48
Week 24
Week 48
PBO
TREMFYA 100 mg
q8w
TREMFYA 100 mg
q8w
PBO
TREMFYA 100 mg
q8w
TREMFYA 100 mg
q8w
PBO
TREMFYA 100 mg
q8w
TREMFYA 100 mg
q8w
MTX
4/27
(15)
47/75
(63)
55/75
(73)
3/27
(11)
25/75
(33)
47/75
(63)
3/50
(6)
17/105
(16)
26/105
(25)
Other
2/22
(9)
25/47
(53)
29/47
(62)
1/22
(5)
18/47
(38)
19/47
(40)
1/36
(3)
12/69
(17)
21/69
(30)
Abbreviations: BSA, body surface area; csDMARD, conventional synthetic disease-modifying antirheumatic drug;  IGA, Investigator’s Global Assessment; MDA, minimal disease activity; MTX, methotrexate; PASI 100, 100% improvement in Psoriasis Area and Severity Index; PASI 90, ≥90% improvement in Psoriasis Area and Severity Index; PBO, placebo; q8w, every 8 weeks.
aPASI 90/100 was assessed in patients with ≥3% BSA psoriatic involvement and IGA score ≥2 (mild) at baseline (PBO, n=53; TREMFYA, n=133).

Pooled Safety Analysis

Rahman et al (2023)5 summarized pooled safety data of TREMFYA treatment for up to 2 years in patients with active PsA across 4 phase 2/3 clinical trials (Phase 2, DISCOVER-1, DISCOVER-2, and COSMOS).

Study Design/Methods

  • Patients in the Phase 2 and COSMOS clinical trials were randomized to receive either TREMFYA 100 mg q8w or placebo with crossover to TREMFYA 100 mg q8w.
  • Long-term safety included data from all patients treated with ≥1 dose of TREMFYA.
  • The safety reporting periods for TREMFYA exposure were defined as: Phase 2 and COSMOS, week 0-56; DISCOVER-1, week 0-60; DISCOVER-2, week 0-112.
  • Safety data were assessed in an integrated safety analysis through week 24 (placebo-controlled period) and through the end of each study.

Results

Patient Characteristics

Proportion of Patients With Concomitant csDMARDs or MTX Use at Baseline Among Phase 2, DISCOVER-1, DISCOVER-2, and COSMOS Studies5
n (%)
TNFi-naïve
(n=1138)
TNFi-experienced
(n=416)a
Total
(N=1554)
csDMARD
733 (64.41)
272 (65.38)
1005 (64.67)
MTX
637 (55.98)
238 (57.21)
875 (56.31)
Abbreviations: csDMARD, conventional synthetic disease-modifying antirheumatic drug; MTX, methotrexate; TNFi, tumor necrosis factor inhibitor.
aIncluded 8.7%, 31%, and 100% of patients from the Phase 2 study (n=13/149), DISCOVER-1 (n=118/381), and COSMOS (n=285), respectively.
Safety

Incidence of AEs Per 100 PY with and without MTX Use Among Pooled Patients from Phase 2, DISCOVER-1, DISCOVER-2, and COSMOS5
Placebo-Controlled Period (Weeks 0-24)
Through End of Studya
TREMFYA 100 mg q4w
TREMFYA 100 mg q8w
Combined TREMFYA (q4w+q8w)
Placebo
TREMFYA 100 mg q4wb
TREMFYA 100 mg q8wb
Allb
Total number of events/100 PY (95% CI)c
Concomitant MTX use, n
218
361
579
296
432
421
853
   Total PY
101
166
267
133
666
557
1223
   AEs
236.8
(207.77-268.86)
240.4
(217.37-265.10)
239.0
(220.85-258.30)
219.6
(195.18-246.34)
125.6
(117.18-134.36)
160.1
(149.74-170.93)
141.3
(134.70-148.10)
   SAEs
6.0
(2.18-12.94)
5.4
(2.47-10.27)
5.6
(3.14-
9.25)
9.0
(4.66-15.77)
5.1
(3.54-
7.14)
5.9
(4.08-
8.32)
5.5
(4.25-6.96)
   AEs leading
   to D/C
9.9
(4.75-18.22)
3.0
(0.98-
7.01)
5.6
(3.14-
9.25)
5.3
(2.12-10.85)
3.8
(2.43-
5.54)
2.0
(0.99-
3.53)
2.9
(2.06-4.07)
   Infections
58.5
(44.51-75.42)
62.0
(50.52-75.06)
60.6
(51.63-
70.68)
67.0
(53.76-82.39)
38.9
(34.30-43.93)
46.4
(40.99-52.50)
42.4
(38.78-46.16)
   Serious
   infections
2.0
(0.24-
7.16)
0.6
(0.02-
3.35)
1.1
(0.23-
3.28)
3.8
(1.22-
8.78)
1.5
(0.72-
2.76)
1.3
(0.51-
2.59)
1.4
(0.81-2.23)
   Opportunistic
   infections
0.0
(0.00-
2.97)
0.0
(0.00-
1.80)
0.0
(0.00-
1.12)
0.0
(0.00-
2.25)
0.2
(0.00-
0.84)
0.2
(0.00-
1.00)
0.2
(0.02-0.59)
   GI-related
   SAEs
0.0
(0.00-
2.97)
0.0
(0.00-
1.80)
0.0
(0.00-
1.12)
0.8
(0.02-
4.19)
0.2
(0.00-
0.84)
0.2
(0.00-
1.00)
0.2
(0.02-0.59)
   Malignancies
0.0
(0.00-
2.97)
1.2
(0.15-
4.34)
0.8
(0.09-
2.70)
0.8
(0.02-
4.19)
0.0
(0.00-
0.45)
0.4
(0.04-
1.30)
0.2
(0.02-0.59)
   MACEs
1.0
(0.03-
5.52)
0.6
(0.02-
3.35)
0.8
(0.09-
2.70)
0.8
(0.02-
4.19)
0.3
(0.04-
1.09)
0.4
(0.04-
1.30)
0.3
(0.09-0.84)
No concomitant MTX use, n
155
303
458
221
293
362
655
   Total PY
71
139
210
97
440
462
902
   AEs
202.8
(171.15-238.64)
223.4
(199.17-249.64)
216.4
(196.94-237.19)
226.4
(197.45-258.51)
143.3
(132.31-154.90)
159.8
(148.52-171.80)
151.8
(143.82-160.01)
   SAEs
4.2
(0.87-12.26)
4.3
(1.59-
9.41)
4.3
(1.96-
8.12)
8.3
(3.57-16.30)
5.2
(3.31-
7.84)
6.7
(4.56-
9.53)
6.0
(4.50-7.81)
   AEs leading
   to D/C
2.8
(0.34-10.11)
4.3
(1.59-
9.41)
3.8
(1.64-
7.50)
3.1
(0.64-
9.07)
2.0
(0.93-
3.88)
2.8
(1.50-
4.81)
2.4
(1.53-3.69)
   Infections
68.5
(50.70-90.61)
55.5
(43.78-69.34)
59.9
(49.91-
71.34)
60.0
(45.54-77.53)
43.1
(37.22-49.73)
39.8
(34.30-46.04)
41.5
(37.36-45.88)
   Serious
   infections
1.4
(0.04-
7.79)
0.7
(0.02-
4.01)
1.0
(0.12-
3.44)
2.1
(0.25-
7.47)
1.6
(0.64-
3.27)
2.2
(1.04-
3.98)
1.9
(1.10-3.02)
   Opportunistic
   infections
0.0
(0.00-
4.19)
0.0
(0.00-
2.16)
0.0
(0.00-
1.42)
0.0
(0.00-
3.10)
0.0
(0.00-
0.68)
0.2
(0.01-
1.21)
0.1
(0.00-0.62)
   GI-related
   SAEs
0.0
(0.00-
4.19)
0.7
(0.02-
4.01)
0.5
(0.01-
2.65)
2.1
(0.25-
7.47)
0.4
(0.05-
1.64)
0.4
(0.05-
1.56)
0.4
(0.12-1.14)
   Malignancies
0.0
(0.00-
4.19)
0.7
(0.02-
4.01)
0.5
(0.01-
2.65)
0.0
(0.00-
3.10)
0.4
(0.05-
1.64)
0.4
(0.05-
1.56)
0.4
(0.12-
1.14)
   MACEs
0.0
(0.00-
4.19)
0.0
(0.00-
2.16)
0.0
(0.00-
1.42)
0.0
(0.00-
3.10)
0.2
(0.01-
1.27)
0.0
(0.00-
0.65)
0.1
(0.00-0.62)
Abbreviations: AE, adverse event; CI, confidence interval; D/C, discontinuation; GI, gastrointestinal; MACE, major adverse cardiovascular event; MTX, methotrexate; PY, patient-years; q4w, every 4 weeks; q8w, every 8 weeks; SAE, serious adverse event.
aIncludes data through week 56 in Phase 2 and COSMOS, week 60 in DISCOVER-1, and week 112 in DISCOVER-2.
bIncludes patients randomized to the placebo groups who crossed over to TREMFYA; only data on and after the administration of the first dose of TREMFYA were included.
cConfidence intervals based on exact method assuming the observed number of events followed a Poisson distribution.

Proportion of Patients With Grade 1 ALT/AST Elevations Stratified by MTX Use Among Pooled Patients from Phase 2, DISCOVER-1, DISCOVER-2, and COSMOS5
Week 24
≤2 Years
Placeboa
Combined TREMFYA (q4w+q8w)
All TREMFYAa
Baseline MTX use, N
294
755
847
   ALT increased, %
31.6
33.6
40.1
   AST increased, %
22.4
21.4
28.6
Baseline no MTX use, N
220
458
655
   ALT increased, %
20.5
26.0
34.0
   AST increased, %
14.1
15.9
24.7
Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; MTX, methotrexate; q4w, every 4 weeks; q8w, every 8 weeks.
aFor patients in the placebo group who crossed over to TREMFYA, only data on and after the administration of the first dose of TREMFYA were included.

Rahman et al (2022)6 reported the pooled safety results of TREMFYA 100 mg q4w and q8w in patients with active PsA through 1 year from DISCOVER-1, 2 years from DISCOVER-2, and 1 year from a phase 2 study.

Study Design/Methods

  • In the phase 2 study, patients with active PsA (≥3% body surface area affected by PsO, ≥3 tender joints, ≥3 swollen joints, and C-reactive protein levels ≥0.3 mg/dL) were randomized (2:1) to receive TREMFYA 100 mg SC (at weeks 0 and 4 and then q8w) or placebo.
  • The study designs for DISCOVER-1 and DISCOVER-2 are presented in Figure: DISCOVER-1 Study Design and Figure: DISCOVER-2 Study Design, respectively.

Results

Patient Characteristics

Proportion of Patients with Concomitant nbDMARD or MTX Use at Baseline Among DISCOVER-1, DISCOVER-2, and Phase 2 Patients6
TREMFYA
100 mg q4w
(N=373)
TREMFYA
100 mg q8w
(N=475)
TREMFYA Comb (N=848)a
PBO
(N=421)
Total
(N=1269)
nbDMARD
67.6
63.2
65.1
64.8
65.0
MTX
58.4
53.9
55.9
58.4
56.7
Abbreviations: comb, combined; MTX, methotrexate; nbDMARD, nonbiologic disease-modifying antirheumatic drug; PBO, placebo; q4w, every 4 weeks; q8w, every 8 weeks.
aComb patients treated with TREMFYA q4w and q8w (including patients who crossed over from PBO).
Safety

Pooled Incidences of Clinical Laboratory Abnormalities According to the NCI-CTCAE Grade Among Phase 2, DISCOVER-1, and DISCOVER-2 Patients6
PBO-Controlled (Weeks 0-24)
Through 2 Years
PBOa
TREMFYA 100 mg q4w
TREMFYA 100 mg q8w
TREMFYA
100 mg q4w
TREMFYA
100 mg q8w
PBO→ TREMFYA q4wb
PBO→ TREMFYA
q8wb
TREMFYA
Combc
Baseline MTX use, N
244
216
254
216
254
213
11
694
ALT increased, %d
   Grade 1
34.4
38.0
32.3
44.9
42.5
37.6
36.4
41.6
   Grade 2
2.0
3.2
2.0
5.6
3.5
3.8
0
4.2
   Grade 3
0.4
0.9
0.8
1.4
1.6
0.5
0
1.2
   Grade 4
0
0
0
0
0
0
0
0
AST increased, %e
   Grade 1
24.6
25.9
18.9
32.9
29.5
25.4
36.4
29.4
   Grade 2
0.4
1.9
2.4
4.2
3.9
2.3
9.1
3.6
   Grade 3
0.4
0.9
0.4
1.4
0.4
0.9
0
0.9
   Grade 4
0
0
0
0
0
0
0
Blood bilirubin increased, %f
   Grade 1
0.4
6.5
3.1
9.7
4.3
5.6
0
6.3
   Grade 2
0.8
0.5
0.8
1.4
2.4
1.4
0
1.7
   Grade 3
0
0
0
0
0
0
0
0
   Grade 4
0
0
0
0
0
0
0
0
No baseline MTX use, N
175
155
219
155
219
138
17
529
ALT increased, %d
   Grade 1
22.9
31.0
24.7
43.2
33.8
30.4
47.1
36.1
   Grade 2
0
1.9
0.5
5.2
2.3
2.2
0
3.0
   Grade 3
1.1
1.3
0.5
1.3
0.5
0
0
0.6
   Grade 4
0.6
0
0
0
0
0
0
0
AST increased, %e
   Grade 1
13.7
15.5
16.0
29.0
23.3
24.6
35.3
25.7
   Grade 2
0.6
1.3
1.4
3.2
3.2
1.4
0
2.6
   Grade 3
1.7
2.6
0.5
3.9
1.4
0.7
0
1.9
   Grade 4
0
0
0
0
0
0
0
0
Blood bilirubin increased, %f
   Grade 1
2.3
4.5
5.0
6.5
4.6
4.3
5.9
5.1
   Grade 2
1.7
0.6
1.8
0.6
4.1
0.7
5.9
2.3
   Grade 3
0
0
0
0
0
0
0
0
   Grade 4
0
0
0
0
0
0
0
0
Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; comb, combined; MTX, methotrexate; NCI-CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events; PBO, placebo; q4w, every 4 weeks; q8w, every 8 weeks; ULN, upper limit of normal.
aFor patients in the PBO group who crossed over to TREMFYA q4w, only data prior to the first dose of TREMFYA were included.
bFor patients in the PBO group who crossed over to TREMFYA, only data on and after the administration of the first dose of TREMFYA were included.
cComb patients treated with TREMFYA q4w and q8w (including patients who crossed over from PBO).
dGrade 1, >ULN to ≤3.0×ULN; grade 2, >3.0 to ≤5×ULN; grade 3, >5 to <20×ULN; grade 4, ≥20×ULN.
eGrade 1, >ULN to 3.0×ULN; grade 2, >3.0 to 5×ULN; grade 3, >5 to <20×ULN; grade  4, ≥20×ULN.
fGrade 1, >ULN to ≤1.5×ULN; grade 2, >1.5 to ≤3×ULN; grade 3, >3 to ≤10×ULN; grade 4, >10×ULN.

LITERATURE SEARCH

A literature search of MEDLINE®, EMBASE®, BIOSIS Previews®, and DERWENT® (and/or other resources, including internal/external databases) was conducted on 06 February 2025.

 

References

Show
1 Ritchlin CT, Mease PJ, Boehncke WH, et al. Sustained and improved guselkumab response in patients with active psoriatic arthritis regardless of baseline demographic and disease characteristics: pooled results through week 52 of two phase III, randomised, placebo-controlled studies. RMD Open. 2022;8(1):e002195.  
2 Ritchlin CT, Mease PJ, Boehncke WH, et al. Stringent disease activity control at 2 years across psoriatic arthritis domains irrespective of baseline characteristics in patients treated with guselkumab: post hoc analysis of a phase 3, randomized, double-blind, placebo-controlled study. Poster presented at: American College of Rheumatology (ACR) Convergence; November 10-14, 2022; Philadelphia, PA.  
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6 Rahman P, Ritchlin CT, Mease PJ, et al. Long-term safety of guselkumab (TREMFYA®) in patients with active psoriatic arthritis: pooled results from 3 randomized clinical trials through up to 2 years. Poster presented at: German Society for Rheumatology (DGRh) Congress; August 31-September 3, 2022; Berlin, Germany.  
7 Deodhar A, Helliwell PS, Boehncke WH, 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 [published correction appears in Lancet. 2020 Apr 4;395(10230):1114]. Lancet. 2020;395(10230):1115-1125.  
8 Deodhar A, Helliwell PS, Boehncke WH, et al. Supplement to: 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.  
9 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 [published correction appears in Lancet. 2020 Apr 4;395(10230):1114]. Lancet. 2020;395(10230):1126-1136.  
10 Mease PJ, Rahman P, Gottlieb AB, et al. Supplement to: Guselkumab in biologic-naive patients with active psoriatic arthritis (DISCOVER-2): a double-blind, randomised, placebo-controlled phase 3 trial [published correction appears in Lancet. 2020 Apr 4;395(10230):1114]. Lancet. 2020;395(10230):1126-1136.  
11 Ritchlin CT, Mease PJ, Boehncke WH, et al. Supplement to: Sustained and improved guselkumab response in patients with active psoriatic arthritis regardless of baseline demographic and disease characteristics: pooled results through week 52 of two phase III, randomised, placebo-controlled studies. RMD Open. 2022;8(1):e002195.  
12 Coates LC, Gossec L, Theander E, et al. Efficacy and safety of guselkumab in patients with active psoriatic arthritis who are inadequate responders to tumour necrosis factor inhibitors: results through one year of a phase IIIb, randomised, controlled study (COSMOS). Ann Rheum Dis. 2022;81(3):359-369.