Biologics in the management of psoriasis

Figures & data

Table 1 Recommended actions before initiating biologic therapy for psoriasis and psoriatic arthritis

Age appropriate history

Physical examination

Current medication list

Baseline laboratory tests

Liver function tests

Complete blood cell count, including platelet count

Hepatitis panel

Tuberculosis skin test (PPD)

Urine pregnancy test

Ensure up-to-date status in standard vaccinations, including pneumococcal, hepatitis A and B, influenza, tetanus-diphtheria

Abbreviation: PPD, purified protein derivative.

Table 2 Clinical trials of biologic agents for chronic plaque psoriasis

Lead author, journala	Designb	N	Dose, route, frequencyc	Efficacyd	Safetye
Etanercept
Gottlieb, Arch^Citation41	R, DB, PC, MC	112	Weeks 0–24: 25 mg vs placebo SC BIW	Week 12 PASI 75:  etanercept 25 mg BIW: 30%  placebo: 2% Week 24 PASI 75:  etanercept 25 mg BIW: 56%  placebo: 5%	SAE: Similar incidence between groups. No SAE considered related to drug. AE: Similar incidence between groups. Infection: URI more common in etanercept (35%) than placebo (20%).
Leonardi, NEJM^Citation42	R, DB, PC, MC	652	Weeks 0–24: 50 mg SC BIW vs 25 mg SC BIW vs 25 mg SC QW vs Weeks 0–12: placebo + Weeks 13–24: 25 mg SC BIW	Week 12 PASI 75:  etanercept 50 mg BIW: 49%  etanercept 25 mg BIW: 34%  etanercept 25 mg QW: 14%  placebo: 4% Week 24 PASI 75:  etanercept 50 mg BIW: 59%  etanercept 25 mg BIW: 44%  etanercept 25 mg QW: 25%  placebo → 25 mg BIW: 33%	SAE: Not reported. AE: Similar incidence between groups. Most were mild–moderate. Infection: Similar incidence between groups.
Papp, Br J Derm^Citation45	R, DB, PC, MC	583	Weeks 0–12: 25 vs 50 mg vs placebo SC BIW Weeks 13+: OL extension 25 mg SC BIW	Week 12 PASI 75:  etanercept 50 mg BIW: 49%  etanercept 25 mg BIW: 34%  placebo: 3% Week 24 PASI 75:  50 mg → 25 mg BIW: 54%  continuous 25 mg BIW: 45%  placebo → 25 mg BIW: 28%	SAE: Incidence by treatment group not reported. Total N = 12 in first 12 weeks. AE: Similar incidence between groups. Most were mild-moderate. Infection: Similar incidence between groups.
Tyring, Lancet^Citation61 Tyring, Arch^Citation47	R, DB, PC, MC	618	Weeks 0–12: 50 mg vs placebo SC BIW Weeks 13+: OL extension (50 mg SC BIW)	Week 12 PASI 75:  etanercept 50 mg BIW: 47%  placebo: 5% Week 24 PASI 75:  continuous 50 mg BIW: 60%   placebo → 50 mg BID 48%	SAE: Similar incidence between groups. AE: More patients on etanercept (11%) than placebo (1%) had ≥1 injection site reaction. All other AE similar incidence between groups. Infection: More patients on etanercept (28%) than placebo (23%) had ≥1 infection.
Paller, NEJM^Citation65	R, DB, PC, MC	211	In subjects 4–17 years old: Weeks 0–12: 0.8 mg/kg (max 50 mg) vs placebo SC QW Weeks 13–35: OL extension Weeks 36–48: withdrawal re-treatment period	Week 12 PASI 75:  etanercept 0.8 mg/kg QW: 57%  placebo: 11% Week 24 PASI 75:  continuous-etanercept: 69%  placebo → etanercept: 62%	SAE: No SAE in placebo-controlled phase. AE: Similar rate of AE between groups. Most were mild-moderate. Infection: Similar rate of infection between groups.
Infliximab
Gottlieb, JAAD^Citation72	R, DB, PC, MC	249	Weeks 0, 2, 6: 3 vs 5 mg/kg vs placebo IV	Week 10 PASI 75:  infliximab 5 mg/kg: 88%  infliximab 3 mg/kg: 72%  placebo: 6%	SAE: All in infliximab (6%) of which 33% considered “reasonably related” to drug. AE: More patients on infliximab (78%) than placebo (63%) reported ≥1 AE. Infection: One serious infection in infliximab group; none in placebo.
Reich, Lancet^Citation75	R, DB, PC, MC	378	Weeks 0, 2, 6, then Q8W: 5 mg/kg IV vs Weeks 0–22: placebo + Weeks 24, 26, 30, then Q8W: infliximab 5 mg/kg IV	Week 10 PASI 75:  infliximab 5 mg/kg: 80%  placebo: 3% Week 24 PASI 75:  infliximab 5 mg/kg: 82%  placebo: 4%	SAE: Higher incidence in infliximab (6%) than placebo (3%). AE: More patients on infliximab (82%) than placebo (71%) reported ≥1 AE. Infection: Similar incidence between groups.
Menter, JAAD^Citation73	R, DB, PC, MC	835	Weeks 0, 2, 6: 3 mg/kg vs 5 mg/kg vs placebo IV Week 14 re-randomize: continuous infliximab 3 vs 5 mg/kg Q8W or infliximab only when <PASI 75 vs placebo crossover to 5 mg/kg	Week 10 PASI 75:  infliximab 5 mg/kg: 76%  infliximab 3 mg/kg: 70%  placebo: 2% Week 26 PASI 75:  infliximab 3 mg/kg Q8W: 65%  infliximab 3 mg/kg as needed: 42%  infliximab 5 mg/kg Q8W: 78%  infliximab 5 mg/kg as needed: 58%	SAE: Similar incidence between groups. AE: More patients on infliximab 3 mg/kg (63%) and 5 mg/kg (69%) than placebo (56%) reported ≥1 AE. Infection: Similar incidence between groups. Two cases tuberculosis in infliximab-treated patients.
Adalimumab
Gordon, JAAD^Citation80	R, DB, PC, MC	147	Weeks 0–1: 80 mg SC QW + Weeks 2–60: 40 mg SC QW vs Week 0: 80 mg SC + Weeks 1–60: 40 mg SC EOW vs Weeks 0–11: placebo + Week 12: 80 mg SC + Weeks 13–60: 40 mg SC EOW	Week 12 PASI 75:  adalimumab QW: 80%  adalimumab EOW: 53%  placebo: 4%	SAE: Higher incidence in adalimumab 40 mg QW (8%) vs 40 mg EOW (2%) vs placebo (0%). AE: Similar incidence between groups. Most were mild-moderate, unrelated. Infection: Similar incidence between groups.
Menter, JAAD^Citation82	R, DB, PC, MC	1212	Weeks 0–15 (RCT): placebo vs 80 mg SC × 1 then 40 mg SC EOW Weeks 16–33 (OL): 40 mg SC EOW (if PASI 75) Weeks 34–50 (RCT): 40 mg SC EOW vs placebo (if PASI 75)	Week 16 PASI 75:  adalimumab: 71%  placebo: 7% Week 33–52 loss of response:  placebo: 28%  continuous adalimumab: 5%	SAE: Similar incidence between groups. AE: Higher in adalimumab (62%) than placebo (56%). Most were mild–moderate. Infection: Higher in adalimumab (29%) than placebo (22%).
Saurat, Br J Derm^Citation81	R, DB, PC, MC	271	Weeks 0–16: 80 mg SC × 1 then 40 mg EOW vs methotrexate 7.5–25 mg po QW vs placebo	Week 16 PASI 75:  adalimumab: 80%  methotrexate: 36%  placebo: 19%	SAE: Similar incidence between groups. AE: Similar incidence between groups. Infection: Similar incidence between groups.
Alefacept
Ellis, NEJM^Citation85	R, DB, PC, MC	229	Weeks 0–12: 0.025 mg/kg vs 0.075 mg/kg vs 0.150 mg/kg vs placebo IV QW	Week 14 PASI 75:  alefacept 0.150 mg/kg: 31%  alefacept 0.075 mg/kg: 33%  alefacept 0.025 mg/kg: 21%  placebo: 10%	SAE: None related to alefacept. AE: Accidental injury, dizziness, nausea, chills, cough each ≥5% more common in alefacept than placebo. Infection: Similar incidence between groups.
Krueger, JAAD^Citation87	R, DB, PC, MC	553	7.5 mg vs placebo IV QW × two 12- week courses	1st course PASI 75:  alefacept 7.5 mg IV QW: 28%  placebo: 8% 2nd course PASI 75:  alefacept 7.5 mg IV QW: 37%  placebo: 19%	SAE: None related to alefacept. AE: Chills more common with alefacept (10% vs 1%), most within 24 hours of dose, limited to 1st and 2nd dose. Infection: Similar incidence between groups.
Lebwohl, Arch^Citation88	R, DB, PC, MC	507	Weeks 0–12: 15 mg vs 10 mg vs placebo IM QW	PASI 75:  alefacept 15 mg: 33%  alefacept 10 mg: 28%  placebo: 13%	SAE: Similar incidence between groups. AE: Similar incidence between groups. Infection: Higher in alefacept (15%) than placebo (11%); not significant.
Krueger, JDT^Citation89	MC, OL	A-449 B-340 C-203	Up to three 12-week courses of 15 mg IM QW + other therapy: ~33% none ~33% topical ~33% systemic or UVB	PGA “mild” or better (MOB):  1st course: 30%  2nd course: 38%  3rd course: 40% PGA MOB across all courses:  alefacept 15 mg IM QW: 31–48%  alefacept + topical: 33%–45%  alefacept + UVB: 29%–50%	SAE: Similar incidence between groups. AE: Similar incidence between groups. Infection: No increased risk of infection over multiple courses of treatment.
Ortonne, JEADV^Citation90	R, OL, MC	60	Weeks 0–12: 15 mg IM QW + no UVB vs UVB TIW × 6 weeks vs UVB TIW × 12 weeks	PASI 75:  alefacept 15 mg IM QW: 35%  alefacept + UVB × 6 weeks: 74%  alefacept + UVB × 12 weeks: 81%	SAE: One SAE in subject on alefacept + 6 weeks UVB. Considered unrelated. AE: More common in alefacept + UVB: erythema, skin pain and tenderness. More common in alefacept alone: pruritus. Infection: No serious, severe, or opportunistic infections.
Efalizumab
Lebwohl, NEJM^Citation104	R, DB, PC, MC	597	Weeks 0–12: 1 vs 2 mg/kg vs placebo SC QW Weeks 13–24: ≥PASI 50: 2 mg/kg SC QW vs EOW vs placebo <PASI 50: 4 mg/kg vs placebo SC QW	Week 12 PASI 75:  efalizumab 2 mg/kg QW: 28%  efalizumab 1 mg/kg QW: 22%  placebo: 5% Week 24 PASI 75: ≥PASI 50 at week 12:  efalizumab 2 mg/kg QW: 64% efalizumab 2 mg/kg EOW: 52%  placebo: 12% <PASI 50 at week 12:  efalizumab 4 mg/kg QW: 13%  placebo: 2%	SAE: Similar incidence between groups. AE: Acute AE (HA, pain, F/C) more common in efalizumab 1st and 2nd dose. Most mild–moderate. Infection: Similar incidence between groups.
Gordon, JAMA^Citation106 Menter, Arch^Citation107	R, DB, PC, MC MC, OL	556 516	Weeks 0–12: placebo vs efalizumab 0.7 mg/kg SC × 1 then 1 mg/kg SC QW Weeks 13–24: OL extension (1 mg/kg SC QW)	Week 12 PASI 75:  efalizumab: 27%  placebo: 4% Week 24 PASI 75:  continuous efalizumab: 44%  placebo → efalizumab: 24%	SAE: Similar incidence between groups. AE: More acute AE (HA, F/C, myalgias) in efalizumab 1st–2nd doses. Infection: Similar incidence in efalizumab (27%) vs placebo (23%).
Leonardi, JAAD^Citation105	R, DB, PC, MC	498	Weeks 0–12: placebo vs 0.7 mg/kg SC × 1 then 1 mg/kg vs 2 mg/kg SC QW Week 13–24: Re-randomize efalizumab-treated subjects with <PASI 75	Week 12 PASI 75:  efalizumab 2 mg/kg: 27%  efalizumab 1 mg/kg: 39%  placebo: 2% Week 24 PASI 75 (patients with week 12 <PASI 75):  efalizumab 2 mg/kg: 20%  efalizumab 1 mg/kg: 21%  placebo: 7%	SAE: Similar incidence between groups. AE: More acute AE (HA, F/C) in efalizumab 1st–2nd doses. Infection: Similar incidence between groups.
Papp, Int J Derm^Citation142	R, DB, PC, MC	686	Weeks 0–12: placebo vs 0.7 mg/kg SC × 1 then 1 mg/kg SC QW	Week 12 PASI 75:  efalizumab: 24%  placebo: 3%	SAE: Similar incidence between groups. AE: Higher rate of AE in efalizumab (82%) than placebo (73%), including acute AE with 1st–2nd doses. Infection: Similar incidence between groups.
Dubertret, Br J Derm^Citation143	R, DB, PC, MC	793	Weeks 0–12: placebo vs 0.7 mg/kg SC × 1 then 1 mg/kg SC QW	Week 12 PASI 75:  efalizumab: 31%  placebo: 4%	SAE: Similar incidence between groups. AE: More acute AE (HA, F/C, myalgias) in efalizumab (40%) than placebo (22%). Infection: Higher rate in efalizumab (28%) than placebo (20%).
Ustekinumab
Krueger, NEJM^Citation134	R, DB, PC, MC	320	45 vs 90 mg SC × 1 (week 0) vs 45 vs 90 mg SC QW (weeks 0–4) vs placebo	Week 12 PASI 75:  ustekinumab 90 mg QW × 4: 81%  ustekinumab 45 mg QW × 4: 67%  ustekinumab 90 mg × 1: 59%  ustekinumab 45 mg × 1: 52%  placebo: 2%	SAE: Higher rate in ustekinumab (4%) vs placebo (1%); not significant. AE: Similar incidence between groups. Infection: Similar incidence between groups.
Leonardi, Lancet^Citation137	R, DB, PC, MC	766	45 vs 90 mg vs placebo SC at weeks 0, 4, then Q12W Placebo crossover at week 12	Week 12 PASI 75:  ustekinumab 90 mg: 66%  ustekinumab 45 mg: 67%  placebo: 3% Week 28 PASI 75:  ustekinumab 90 mg: 79%  ustekinumab 45 mg: 71%  crossover to 90 mg: 85%  crossover to 45 mg: 66%	SAE: Similar incidence between groups. AE: Similar incidence between groups. Infection: Similar incidence between groups.
Papp, Lancet^Citation136	R, DB, PC, MC	1230	45 vs 90 mg SC vs placebo at weeks 0, 4 then Q12W Placebo crossover at week 12	Week 12 PASI 75:  ustekinumab 90 mg: 76%  ustekinumab 45 mg: 67%  placebo: 4% Week 28 PASI 75:  ustekinumab 90 mg: 79%  ustekinumab 45 mg: 70%  crossover to 90 mg: 79%  crossover to 45 mg: 70%	SAE: Similar incidence between groups. AE: Similar incidence between groups. Infection: Similar incidence between groups.
ABT-874
Kimball, Arch^Citation139	R, DB, PC, MC	180	200 mg SC QW vs 200 mg SC EOW vs 200 mg SC QW × 4 vs 100 mg SC EOW vs 200 mg SC × 1	Week 12 PASI 75:  ABT-874 200 mg QW: 90%  ABT-874 200 mg EOW: 93%  ABT-874 200 mg × 4: 90%  ABT-874 100 mg EOW: 93%  ABT-874 200 mg × 1: 63%  placebo: 3%	SAE: Similar incidence between groups. AE: Significantly more AE at least “possibly related to study drug” in all ABT-874 groups than placebo; most were injection site reactions. Infection: Similar incidence between groups.

a Notes: Arch, Arch Dermatol; Br J Derm, Br J Dermatol; Int J Derm, Int J Dermatol; JAAD, J Am Acad Dermatol; JDT, J Dermatolog Treat; JEADV, J Eur Acad Dermatol Venereol; NEJM, N Engl J Med.

b R, randomized; DB, double-blind; PC, placebo-controlled; MC, multi-center; OL, open-label.

c SC, subcutaneous; IV, intravenously; IM, intramuscular; QW, once weekly; BIW, twice weekly; TIW, three times weekly; QXW, every X weeks.

d PASI, psoriasis area and severity index; PASI X, X % or greater decrease in PASI score; PGA, physician’s global assessment; re-tx, retreatment.

e (S)AE, (serious) adverse event; URI, upper respiratory tract infection; HA, headache; F/C, fever/chills.

Table 3 Recommended monitoring during treatment with tumor necrosis factor-alpha inhibitors

In all patients:

Periodic history and physical examination

Periodic liver function tests

Periodic complete blood count

Yearly tuberculosis skin test (PPD)

In patients with hepatitis C:

Periodic monitoring of liver function tests

Periodic hepatitis C viral load

Abbreviation: PPD, purified protein derivative.

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