Monoclonal antibodies inhibiting IL-12, -23, and -17 for the treatment of psoriasis

Figures & data

Figure 1. The pathogenesis of psoriasis. Abbreviations: DDC – dermal dendritic cells, AMP – anti-microbial peptides, IL – interleukin, Th1 – T-helper type 1, Th17 – T-helper type 17, Th22 – T-helper type 22, TNF-α – tumor necrosis factor – α, INF-γ – interferon-gamma.

Table 1. Dosing regimens of approved monoclonal antibodies targeting IL-12/23 and IL-17.

	Target	Loading dosing	Maintenance dosing
Ustekinumab (Stelara)	P40 subunit of IL12 and 23	Weight ≤100 kg: 45 mg SC at weeks 0 and 4	Weight ≤100 kg: 45 mg SC every 12 weeks starting at week 16
		Weight > 100 kg: 90 mg SC at weeks 0 and 4	Weight > 100 kg: 90 mg SC every 12 weeks starting at week 16
Secukinumab (Cosentyx)	IL-17A	300 mg SC weekly at weeks 0, 1, 2, 3, and 4	300 mg SC every 4 weeks starting at week 8
Ixekixumab (Taltz)	IL-17A	160 mg SC at week 0, then 80 mg SC at weeks 2, 4, 6, 8,10, and 12	80 mg SC every 4 weeks starting at week 16
Brodalumab (Siliq)	IL-17RA	210 mg at Weeks 0, 1, and 2	210 mg every 2 weeks starting at week 4

Table 2. PASI 75 and PASI 90 rates from Phase III trials of TNFα inhibitors vs. newer agents targeting IL-12, -23, and -17 for the treatment of psoriasis.

		PASI 75			PASI 90
	Maintenance dosing	Week 10	Week 12	Week 16	Week 10	Week 12	Week 16
TNFα inhibitors
Etanercept (Enbrel) ^[95]	50 mg BIW		47			19
Adalimumab (Humira) ^[96]	40 mg Q2W		68	71		37	45
Infliximab (Remicade) ^[97]	5 mg/kg Q8W	80–85			57–60
Newer Agents
Ustekinumab (Stelara)^[Citation21,Citation22]	45 mg Q12W		66.7–67.1			41.6–42.3
	90 mg Q12W		66.4–75.7			36.7–50.9
Secukinumab (Cosentyx)^[Citation40–Citation43]	300 mg Q4W		77.1–30.1			54.2–59.2
	150 mg Q4W		67.0–84.4			39.1–41.9
Ixekixumab (Taltz)^[Citation54–Citation56]	80 mg Q2W		87.3–89.7			68.1–70.9
	80 mg Q4W		77.5–84.2			59.7–65.3
Brodalumab (Siliq)^[Citation70–Citation73]	210 mg Q2W		83.3–86.3			68.9–70.3
	140 mg Q2W		60.3–69.2			42.5–52.0
Guselkumab ^[Citation84,Citation85]	100 mg Q8W			86.3–91.2			70.0–73.3
Tildrakizumab ^[91]	100 or 200 mg Q12W		63.0			36.0–37.0

Abbreviations: BIW-twice weekly, NA-not available, PASI-Psoriasis Area and Severity Index, Q2W-every 2 weeks, Q4W-every 4 weeks, Q8W-every 8 weeks, Q12W-every 12 weeks, TNF-tumor necrosis factor

Table 3. The most common side effects of TNFα inhibitors vs. newer agents targeting IL-12, -23, and -17 for the treatment of psoriasis.

	Most common side effects	Boxed warnings
TNFα inhibitors
Etanercept (Enbrel) ^[98]	>5%: infections and injection site reactions	Serious infections, malignancies
Adalimumab (Humira) ^[99]	>10%: infections (e.g. upper respiratory, sinusitis), injection site reactions, headache and rash	Serious infection, malignancy
Infliximab (Remicade) ^[100]	>10%: infections (e.g., upper respiratory, sinusitis, and pharyngitis), infusion-related reactions, headache, and abdominal pain	Serious infection, malignancy
Newer Agents
Ustekinumab (Stelara) ^[16]	≥3%: nasopharyngitis, URTI, headache, and fatigue	None
Secukinumab (Cosentyx) ^[37]	≥1%: nasopharyngitis, diarrhea, URTI	None
Ixekixumab (Taltz) ^[51]	≥1%: injection site reactions, URTI, nausea, and tinea infections	None
Brodalumab (Siliq) ^[62]	≥1%: arthralgia, headache, fatigue, diarrhea, oropharyngeal pain, nausea, myalgia, injection site reactions, influenza, neutropenia, tinea infections	Suicidal ideation and behavior
Guselkumab^[Citation84,Citation85]	nasopharyngitis, headache, URTI	Not Applicable
Tildrakizumab^[Citation86,Citation87]	headache, nasopharyngitis, URTI, cough	Not Applicable
Risankizumab ^[93]	URTI, nasopharyngitis, and headache	Not Applicable

Abbreviations: URTI-upper respiratory tract infection

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