Network meta-analysis comparing the efficacy of biologic treatments for achieving complete resolution of nail psoriasis

Figures & data

Table 1. Design features of clinical trials included in the network meta-analysis.

Study	Treatment	Design	No. and type of pts	% of pts with NP	Time of evaluation	Primary endpoint	Nail outcomes evaluated (bolded outcomes used in the NMA) [fingernail or toenail assessment]	Handling of missing data	Nail psoriasis minimum required score
AMAGINE-2 and -3 (7,39)	Brodalumab 210 mg weeks 0, 1, 2 then q2wk	Post hoc analysis of r, db, mc, pc^b trials	410 Pso	25.4	Weeks 12‒52	PASI75, PASI100, sPGA 0 or 1 (week 12)	NAPSI improvement, % pts with NAPSI = 0 [nail type not specified]	As observed	NAPSI ≥ 6
	Ustekinumab 45/90 mg^a weeks 0, 4 then q12wk		183 Pso	97.8
Elewski et al. (14)	Adalimumab 80 mg week 0 then 40 mg q2wk starting week 1	r, db, mc, pc	109 Pso + NP	100	Weeks 16, 26	TF mNAPSI75 (week 26)	TF mNAPSI75, TF NAPSI improvement, % pts with TF mNAPSI = 0, NP pain improvement on NRS, NPPFS improvement [fingernail]	Multiple imputation	TF mNAPSI ≥ 20; target fingernail mNAPSI ≥ 8; PGA-F ≥ moderate severity
	Placebo		108 Pso + NP	100
EXPRESS (9)	Infliximab 5 mg/kg week 0, 2, 6 then q8week	Post hoc analysis of r, db, mc, pc trial	378 Pso^c	81.8^c	Weeks 10‒50	PASI75 (week 10)	NAPSI, nail matrix, and nail bed score improvement, % pts with NAPSI = 0 [fingernail]	As observed	NAPSI ≥ 1
	Placebo
IXORA-R (12,13)	Ixekizumab 160 mg week 0 then 80 mg q2week from week 2 to 12 then 80 mg q4week	Post hoc analysis of r, db, mc trial	520 Pso	51	Weeks 12, 24	PASI100 (week 12)	% pts with PGA-F 0 or 1 with ≥ 2-point improvement (week 24), % pts with PGA-F = 0 (week 24) [fingernail]	Non-responder imputation	PGA-F ≥ 1
	Guselkumab 100 mg week 0, 4 then q8week		507 Pso	47
IXORA-S (11)	Ixekizumab 160 mg week 0 then 80 mg q2week from week 2 to 12 then 80 mg q4week	Post hoc analysis of r, db, mc trial	136 Pso	61.8	Weeks 2‒52	PASI90 (week 12)	% pts with NAPSI = 0, NAPSI improvement [fingernail]	Non-responder imputation	NAPSI ≥ 1
	Ustekinumab 45/90 mg^a week 0, 4 then q12week		166 Pso	63.3
SPIRIT-H2H (10,16)	Ixekizumab 160 mg week 0 then 80 mg q2week from week 2 to 12 then 80 mg q4week	r, nb (ba)	283 Pso^e + PsA	68	Weeks 4‒52	PASI100 plus ACR50 (week 24)	% pts with NAPSI = 0, NAPSI improvement [fingernail]	Non-responder imputation	NAPSI ≥ 1
	Adalimumab 80 mg week 0 then 40 mg q2week starting week 1		283 Pso^e + PsA	63
VOYAGE-1 and −2 (15)	Guselkumab 100 mg week 0, 4 then q8week	Post hoc analysis of r, db, mc, pc^b trials	825 Pso	57.4 (overall)	Weeks 16, 24	IGA 0 or 1, PASI90 (week 16)	% pts with PGA-F 0 or 1, % pts with PGA-F = 0, NAPSI improvement, % pts with NAPSI = 0 [fingernail]	Non-responder imputation	PGA-F ≥ 1
	Adalimumab 80 mg week 0 then 40 mg q2wk starting week 1		582 Pso

Note. All agents were administered as per EU labeling (19‒24).

^aWeight-based dosing; ^bdata not reported for placebo, or study design involved early cross-over to active treatment; ^ca total of 378 pts were randomized 4:1 to infliximab or placebo, 373 were assessed for nail disease, and 305/373 (81.8%) had NP at baseline; ^dpercentage of pts with moderate-to-severe NP (PGA-F score ≥ 3); ^eSPIRIT-H2H permitted inclusion of pts with less severe Pso, and these pts received modified dosage regimens of biologics; ≈17‒18% of pts had moderate-to-severe Pso.

ACR50: ≥ 50% improvement in American College of Rheumatology criteria; ba: blinded-assessor; db: double-blind; IGA: Investigator’s Global Assessment; mNAPSI75: ≥75% improvement in modified Nail Psoriasis Severity Index; mc: multicenter; NAPSI: Nail Psoriasis Severity Index; nb: nonblind (open-label); NMA: network meta-analysis; NP: nail psoriasis; NPPFS: Nail Psoriasis Physical Functioning Severity; NRS: numeric rating scale; PASI: Psoriasis Area and Severity Index; PASI75 = 75% improvement in PASI; PASI90 = 90% improvement in PASI; PASI100 = 100% improvement in PASI; pc: placebo-controlled; PGA-F: Physician’s Global Assessment of Fingernail Psoriasis; PsA: psoriatic arthritis; Pso: moderate-to-severe psoriasis; pts: patients; qxwk: every x weeks; r: randomized; sPGA: Static Physician Global Assessment; TF: total fingernail.

Figure 1. Network diagram for complete resolution of nail psoriasis at weeks 24‒26.

Table 2. Baseline patient characteristics from clinical trials included in the network meta-analysis.

Study	Treatment	Age (years)^a [SD]	% Male	Weight (kg)^a [SD]	% Of pts with PsA	Disease (Pso) duration (years)^a [SD]	PASI score^a [SD]	DLQI score^a	PGA-F score^a	NAPSI score^a [SD] (possible range)	mNAPSI score^a
AMAGINE-2 and −3 (7)^b	Brodalumab	NR	NR	NR	20.2	18.8 [11.3]	NR	NR	NR	9.6 [4.0] (0‒32)	NR
	Ustekinumab	NR	NR	NR	20.2	19.3 [11.3]	NR	NR	NR	9.9 [3.6] (0‒32)	NR
Elewski et al. (14)^c	Adalimumab	47.2 [11.9]	88.1	92.0 [19.5]	27.5	19.7 [12.3]	12.3 [8.6]	NR	NR^d	47.9 [16.1] (0‒80)	57.6 [20.2] (0‒130)
	Placebo	46.2 [12.1]	80.6	88.4 [19.4]	29.6	17.7 [13.2]	12.8 [9.4]	NR	NR^d	46.8 [15.5] (0‒80)	58.1 [21.6] (0‒130)
EXPRESS (9)^e	Infliximab	42.6 [11.5]	69.2	NR	31.7	19.4 [11.0]	NR	NR	NR	4.6 [2.0] (0‒8)	NR
	Placebo	44.3 [12.1]	78.5	NR	33.8	17.1 [10.6]	NR	NR	NR	4.3 [1.9] (0‒8)	NR
IXORA-R (12,13)^b	Ixekizumab	49.0 [13.9]	65	96.6 [24.9]	24	17.5 [13.8]	19.5 [7.9]	12.8 [6.9]	NR^f	NR	NR
	Guselkumab	49.0 [14.9]	62	94.6 [24.9]	20	16.3 [13.8]	19.3 [7.1]	13.2 [7.4]	NR^f	NR	NR
IXORA-S (11)^b	Ixekizumab	43.0 [12.0]	71.4	87.5 [21.7]	20.2	19.4 [12.0]	20.2 [9.0]	NR	NR	28.3 [19.9] (0‒80)	NR
	Ustekinumab	45.4 [12.7]	76.2	91.3 [24.4]	17.1	20.2 [11.8]	21.1 [9.2]	NR	NR	24.8 [20.0] (0‒80)	NR
SPIRIT-H2H (10,16)^b	Ixekizumab	47.5 [12.0]	57	85.3 [19.8]	100	16.1 [13.1]	7.9 [8.7]	9.8 [7.6]	NR	19.7 [18.5] (0‒80)	NR
	Adalimumab	48.3 [12.3]	53	81.9 [18.3]	100	14.7 [12.6]	7.7 [7.3]	9.8 [7.6]	NR	19.1 [16.3] (0‒80)	NR
VOYAGE-1 and -2 (15)	Guselkumab	43.8 [12.4]	71.4	NR	18.5	17.9 [12.1]	22.0 [9.1]	14.4 [7.2]	NR	4.8 [2.0] (0‒8)	NR
	Adalimumab	43.0 [12.3]	72.0	NR	18.2	17.3 [11.4]	21.1 [9.0]	14.6 [7.1]	NR	4.5 [2.0] (0‒8)	NR

^aMean values; ^bbaseline characteristics for the overall study population (with or without nail psoriasis), aside from baseline nail-related scores; ^cbaseline characteristics for the overall study population (all pts had nail psoriasis); ^d50.5% and 49.5% of adalimumab recipients had moderate and > moderate PGA-F scores compared with 56.5% and 43.5% of placebo recipients; ^eBaseline characteristics for subgroup of pts with nail psoriasis (i.e. not the overall study population); ^fAt baseline, 16% of pts in the ixekizumab group and 12% of those in the guselkumab group had PGA-F scores ≥3; 51% and 47%, respectively, had baseline PGA-F ≥ 1.

DLQI: Dermatology Life Quality Index; mNAPSI: modified NAPSI; NAPSI: Nail Psoriasis Severity Index; NR: not reported; PASI: Psoriasis Area and Severity Index; PGA-F: Physician’s Global Assessment of Fingernail Psoriasis; PsA: psoriatic arthritis; Pso: psoriasis; pts: patients; SD: standard deviation.

Figure 2. Forest plot of treatment differences (and 95% credibility intervals) for complete resolution of nail psoriasis (Nail Psoriasis Severity Index [NAPSI] = 0, modified NAPSI [mNAPSI] = 0, or Physician’s Global Assessment of Fingernail Psoriasis [PGA-F] = 0) at weeks 24‒26.

Figure 3. Surface Under the Cumulative RAnking (SUCRA) curve ranking plot and related data.

Figure 4. Number needed to treat for complete resolution of nail psoriasis (Nail Psoriasis Severity Index [NAPSI] = 0, modified NAPSI [mNAPSI] = 0, or Physician’s Global Assessment of Fingernail Psoriasis [PGA-F] = 0) at weeks 24‒26 versus placebo.

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