Long term efficacy and safety of etanercept in the treatment of psoriasis and psoriatic arthritis

Figures & data

Figure 1 Plaque psoriasis.

Note: Classic examples of psoriasis which is characterized by well demarcated, erythematous plaques with an overlying silvery scale which can affect any area of the skin.

Figure 2 Psoriatic arthritis.

Notes: Patients with psoriatic arthritis displaying (A) arthritis mutilans, (B) enthesitis of the right Achilles tendon, (C) a right knee effusion and dactylitis of multiple digits, and (D) dactylitis of the fourth toe.

Figure 3 Etanercept molecule.

Note: Used with permission from Amgen Inc. (Thousand Oaks, CA, USA).
Abbreviation: TNF, tumor necrosis factor.

Table 1 Long term etanercept efficacy in psoriasis

Study	Type	Duration	Patients	Outcomes
Krueger et al^Citation14	Open label extension of Phase III trial for nonresponders	60 weeks	157	PASI 50: 55%, PASI 75: 23% at 60 weeks (PASI 50 nonresponders at week 24)
Tyring et al^Citation15	Phase III trial	96 weeks	591	a) Placebo/etanercept group: PASI 50/75/90: 79.1%, 51.6%, and 22.8% at 96 weeks b) Etanercept/etanercept group: PASI 50/75/90: 82.6%, 51.1%, and 23.2% at 96 weeks
Leonardi et al^Citation19	Extension of two Phase III trials	48 up to 72 weeks	912	a) 50 mg QW, no dose escalation group: PASI 50/75/90: 90%, 60%, and 27% at 72 weeks b) 50 mg BIW, dose escalation group: PASI 50/75/90: 83%, 43%, and 10% at 72 weeks
Paller et al^Citation72 (Pediatric)	Open label extension of Phase III trial	96 weeks	140	PASI 50/75/90: 89%, 61%, and 30% at week 96
Papp et al^Citation20	Post hoc analysis	Up to 4 years	506	PGA clear or almost clear 29.2% and 27.8% at 48 months
Esposito et al^Citation70 (Elderly)	Retrospective	156 weeks	61	PASI 75: 83.61% at week 156

Abbreviations: PASI, Psoriasis Area and Severity Index; PGA, Physicians Global Assessment; QW, once weekly; BIW, twice weekly.

Table 2 Long term etanercept efficacy in psoriatic arthritis

Study	Type	Duration	Patients	Outcomes
Mease et al^Citation26	Phase III trial	Up to 48 weeks	205	a) Placebo/etanercept group: ACR 20: ∼25%, ACR 50: ∼5%, PsARC: 23% at week 24 b) Etanercept group: ACR 20: ∼60%, ACR 50: ∼40%, PsARC: 70% at week 24
Mease et al^Citation27	Extension of Phase III trial	Up to 2 years	169	a) Placebo/etanercept group: ACR 20: 63%, ACR 50: 49%, PsARC: 80% at 96 weeks b) Etanercept group: ACR 20: 64%, ACR 50: 44%, PsARC: 84% at 96 weeks
Esposito et al^Citation70	Retrospective	156 weeks	61	DAS44-ESR score decreased from 5.80 to 0.89 at 156 weeks

Abbreviations: ACR 20, Improvement in the American College of Rheumatology scores by 20%; ACR 50, Improvement in the American College of Rheumatology scores by 50%; DAS, Disease Activity Score; DAS44-ESR, rheumatologic disease activity in 44 joints plus the erythrocyte sedimentation rate; PsARC, psoriatic arthritis response criteria.

Table 3 Long term safety of etanercept

Study	Disease	Duration	Patients	AEs (noninfectious)	SAEs (noninfectious)	Infections	Serious Infections	Deaths
Krueger et al^Citation14	Psoriasis	60 weeks	157	212	14	183	1 (cellulitis)	1
Tyring et al^Citation15	Psoriasis	96 weeks	591	158/100 patient-years	7.7/100 patient-years	103.9/100 patient-years	1.2/100 patient-years	0.2/100 patient-years
Leonardi et al^Citation19	Psoriasis	48 up to 72 weeks	912	135.7/100 patient-years	5.6/100 patient-years	95.2/100 patient-years	1.6/100 patient-years	1
Pariser et al^Citation35	Psoriasis	Up to 144 weeks	4,410	194/100 patient-years	6.7/100 patient-years	97.8/100 patient-years	1.2/100 patient-years	13
Papp et al^Citation20	Psoriasis	Up to 4 years	506	1,914	90	96.9/100 patient-years	0.9/100 patient-years	2
Kimball et al^Citation36	Psoriasis	Up to 3 years	2,511	–	208	–	82	30

Abbreviations: AEs, adverse events; SAEs, severe adverse events.

Table 5 Events of medical interest

Study	Disease	Duration	Patients	CHF	Demyelination	Lymphoma	Oportunistic infection	TB
Krueger et al^Citation14	Psoriasis	60 weeks	157	0	0	0	0	0
Tyring et al^Citation15	Psoriasis	96 weeks	591	2	0	1	0	0
Leonardi et al^Citation19	Psoriasis	48 up to 72 weeks	912	0	0	0	0	0
Pariser et al^Citation35	Psoriasis	Up to 144 weeks	4,410	7	2	1	1 (esophageal candidiasis)	0
Papp et al^Citation20	Psoriasis	Up to 4 years	506	1	0	0	0	0
Kimball et al^Citation36	Psoriasis	Up to 3 years	2,511	0	6	2 (expected 2.3 SIR [95% CI] 0.88 [0.11–3.17])	0	0

Abbreviations: CHF, congestive heart failure; CI, confidence interval; SIR, standardized incidence ratio; TB, tuberculosis.

Table 4 Long term risk of malignancies

Study	Disease	Duration	Patients	All malignancies	Malignancies (excluding NMSC)	SCC	BCC
Krueger et al^Citation14	Psoriasis	60 weeks	157	N/A	N/A	N/A	N/A
Tyring et al^Citation15	Psoriasis	96 weeks	591	23 (expected 26 SIR [95% CI] 0.88 [0.56–1.33])	9 (expected 4.77 SIR [95% CI] 1.89 [0.86–3.58])	4 (expected in the Arizona database 2.51 SIR [95% CI] 1.59 [0.43–4.08], in Minnesota database 1.02 SIR [95% CI] 3.91 [1.07–10.01])	7 (expected 10.14 SIR [95% CI] 0.69 [0.28–1.42])
Leonardi et al^Citation19	Psoriasis	48 up to 72 weeks	912	1.5/100 patient-years (expected 1.9–2.9/100 patient-years for less severe and severe psoriasis patients respectively)	N/A	5 (expected in the Arizona database 2.9 [nonsignificant difference], in Minnesota database 1.2 [significant difference])	5
Pariser et al^Citation35	Psoriasis	Up to 144 weeks	4,410	86	30 (expected 26.05 SIR [95% CI] 1.15 [0.78–1.64])	25 (expected in the Arizona database 12.37 SIR [95% CI] 1.78 [1.11–2.69], in Minnesota database 5.14 SIR [95% CI] 4.28 [2.68–6.47])	31 (expected in the Arizona database 50.86 SIR [95% CI] 0.55 [0.37–0.80])
Papp et al^Citation20	Psoriasis	Up to 4 years	506	19 total 1.5/100 patient-years	7 (expected 7.67 SIR [95% CI] 0.91 [0.37–1.88])	4 (expected in the Arizona database 3.71 SIR [95% CI] 1.08 [0.29–2.76], in the Minnesota database 1.49 SIR [95% CI] 2.68 [0.72–6.87])	8 (expected 15.3 SIR [95% CI] 0.52 [0.23–1.03])
Kimball et al^Citation36	Psoriasis	Up to 3 years	2,511	87	39 (expected 40.1 SIR [95% CI] 0.97 [0.69–1.33])	48 (BCC and SCC) (expected 68.3 SIR [95% CI] 0.70 [0.52–0.93])

Abbreviations: BCC, basal cell carcinoma; CI, confidence interval; NMSC, nonmelanoma skin cancer; SCC, squamous cell carcinoma; SIR, standardized incidence ratio; N/A, not applicable.

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