Table 1.

Summary of clinical therapeutic studies with dactylitis as a primary or secondary outcome.

Article	Study Population	Study Type	Study Size	Study Medication	Outcome Variable	Outcome Data	Study Duration	p	Effect Size
Kavanaugh (PALACE 1)³	Multicenter (n = 83) in 13 countries	DB-RPC, crossover at 16 wks	n = 504	APR vs Pbo	No. of dactylitic digits	Mean ± SEM change from baseline at 24 wks: Pbo = −1.3 ± 0.27, APR (40 mg) = −2.0 ± 0.30, APR (60 mg) = −1.8 ± 0.27	24 wks	> 0.05	N/A
Mease (RAPID-PsA)⁴	Multicenter (n = 92) in North America, Latin America, & Europe	DB-RPC to 24 wks, dose-blinded 24–48 wks, open-label 48–216 wks	n = 409	CZP vs Pbo	LDI	Mean change (SD) from baseline at 24 wks: Pbo = −22.0 ± 46.9, CZP (200 mg) = −40.7 ± 34, CZP (400 mg) = −53.5 ± 69.1	24 wks	0.002 (200 mg); ≤ 0.001 (400 mg)	0.50, combined CZP 200 mg and 400 mg doses
Ritchlin (PSUMMIT 2)⁵	Multicenter (n = 189) in North America, Europe, & Asia Pacific regions	DB-RPC, crossover at 24 wks	n = 312	UST vs Pbo	Dactylitis scored 0–3	Change at 24 wks: 64.6% improvement in median dactylitis score in UST 90-mg vs Pbo. Change at 52 wks: median improvement 95% in pooled UST patients	24, 52 wks	> 0.05	0.29, combined UST groups for PSUMMIT1 & 2 pooled data^{^*}
McInnes (PSUMMIT 1)⁶	Multicenter (n = 104) in North America & Europe	DB-RPC, crossover at 24 wks	n = 615	UST vs Pbo	% with dactylitis; dactylitis scored 0–3	Change at 24 wks: % patients with dactylitis in UST (combined 45/90 mg) 56.2% vs 76.1% in Pbo. ∼70% improvement in median dactylitis score in UST (combined) vs Pbo. 100% improvement in dactylitis scores for UST patients out to 52 wks	24, 52 wks	0.001 for % with dactylitis; 0.003 for dactylitis scores	0.29, combined UST groups for PSUMMIT1 & 2 pooled data^{^*}
Gladman⁷	Single Center in Canada cohort	Prospective from historical (10 years)	n = 294	DMARD vs Biologic	% with complete resolution; % with > 50% improvement No. of dactylitic digits	Change at 6 mo, response: Biologic 77.3%, in DMARD 51.5%. Change at 1 year, response: Biologic 87.2%, DMARD 69.9%.	6, 12 mo	N/A	N/A
Kavanaugh (GO-REVEAL)⁸	Multicenter (n = 58 sites) in the US, Canada, & Europe	DB-RPC, crossover at 24 wks	n = 405	GOL vs Pbo	Dactylitis scored 0–3	Mean ± SD change from baseline at 24 wks: Pbo = 57.2 ± 81.2, GOL (combined 50/100 mg) = 76.6 ± 53.5, GOL (100 mg) = 83.0 ± 45.9	24 wks	N/A	N/A
Kavanaugh (GO-REVEAL)⁹	Multicenter (n = 58 sites) in the US, Canada, & Europe	DB-RPC, crossover at 24 wks	n = 405	GOL vs Pbo	Dactylitis scored 0–3	Change at 24 wks, improved: GOL (combined 50/100 mg) 74%, GOL (100 mg) 82%, Pbo 28%. Change at 52 wks: Numerically less (52%) had improvement in Pbo vs GOL combined (76.6%) or GOL 100 mg (82%)	24, 52 wks	0.002 at 24 wks, N/A at 52 wks	N/A
Cantini¹⁰	Single center in Italy	Prospective followup case-control	n = 76	ADM ± MTX	% with dactylitis of hands/feet	Change at 36 mo: data not reported	36 mo	N/A	N/A
Baranauskaite¹¹	Multicenter (n = 25 +B1 sites) in Europe, Middle East, South Africa, & Turkey	OL	n = 115	MTX ± INX	No. of dactylitic digits	Change at 16 wks (median reduction of ≥ 2 dactylitic digits): MTX = no reduction, MTX+INX = magnitude of reduction not reported, but statistically significant	16 wks	0.0006	N/A
Saougou¹²	Single center in Greece	OL	n = 65	ADM (n = 30), ETN (n = 25), INX (n = 10)	% with dactylitis of hands/feet	Change at 60 mo: 22% no longer had dactylitis	60 mo	N/A	N/A
Karanikolas¹³	Single center in Greece	OL	n = 170	ADM ± CyA	Dactylitis scored 0–3	Change at 12 mo (≥ 50% reduction in dactylitis score): CyA = 28.5%, ADM = 75%, CyA+ADM = 100%	12 mo	N/A	N/A
Jung¹⁴	Single center in Germany	OL	n = 20	ANA ± DMARD	Dactylitis score (not described)	Change at 12 wks: 30% of patients had improved dactylitis scores, 5%+worse, 5%+stable, 5% had undulating course	12 wks	N/A	N/A
Gladman¹⁵	Multicenter (n = 24 sites) in Canada	OL	n = 127	ADM (prior treatment failures)	% with in dactylitis ≥ 4 digits of hands/feet, dactylitis scored 0–3	Change at 12 wks: % of patients with ≥ 4 dactylitic digits dropped from 33.9% to 11%. Mean ± SD dactylitis scores decreased from 7.04 ± 6.45 to 2.49 ± 4.68	12 wks	< 0.001 for both outcomes	N/A
Sterry (PRESTA)¹⁶	Multicenter (n = 98 sites) in Europe, Latin America, & Asia Pacific regions	DB-RPC	n = 752	ETN 50 mg twice vs once weekly	Dactylitis scored 0–3	Change at 12, 24 wks: Baseline score decreased 74.3–78.4% at 12 wks and 84.5–84.8% at 24 wks	12, 24 wks	N/A	N/A
Kavanaugh (GO-REVEAL)¹⁷	Multicenter (n = 58 sites) in US, Canada, & Europe	DB-RPC, crossover at 16 wks	n = 405	GOL vs Pbo	% with dactylitis of hands/feet, dactylitis scored 0–3	Change at 14, 24 wks: % of patients with dactylitis was unchanged. Dactylitis scores, median % change: GOL 100 mg = 100% at 14, 24 wks; Pbo = 0 at 14, 24 wks	14, 24 wks	0.009 at 14 wks, < 0.001 at 24 wks	N/A
Gottlieb¹⁸	Multicenter (n = 24 sites) in US, Canada, & Europe	DB-RPC crossover at 12 wks	n = 146	UST vs Pbo	Dactylitis scored 0–3	Change at 12 wks (median [IQR] improvement): UST = 2.0 (0.0–4.0), Pbo = 0.0 (–1.0–1.5)	12 wks	0.0107	N/A
Mease (ADEPT, 2-year data)¹⁹	Multicenter (n = 50 sites) in US, Canada, & Europe	DB-RPC, crossover at 24 wks, OL extension to 120 wks	n = 245	ADM vs Pbo	Dactylitis scored 0–3	Mean ± SD change from baseline at 48 wks: 1.3 ± 4.8, Change at 104 wks: 1.4 ± −3.7	48, 104 wks of treatment	> 0.05	N/A
Healy²⁰	Single-center study in Britain	OL	n = 17	MTX (n = 12), HC (n = 1), ETN (n = 1), INX (n = 1)	LDI, LDI basic, dactylitis scored 0–3, No. dactylitic digits (tender, nontender), No. dactylitic digits (tender), MRI scores	All clinical indices of dactylitis improved during 6-mo period as did MRI scores for the hand or foot; no primary data provided.	6 mo	N/A	N/A
Antoni (IMPACT 1, 2-year data)²¹	Multicenter (n = 9 sites) in Europe, US, & Canada	DB-RPC crossover at 16 wks	n = 104	INX vs Pbo	No. of dactylitic digits	Mean ± SD change from baseline at 50 wks: INX = 0.32 ± 0.96, Change at 98 wks: INX = 0.19 ± 0.72	50, 98 wks	N/A	N/A
Kavanaugh (IMPACT 2, 1-year data)²²	Multicenter (n = 36 sites) in US, Canada, & Europe	DB-RPC crossover at 24 wks (early escape at 16 wks)	n = 200	INX vs Pbo	% with dactylitis of hands/feet	Change at 24 wks, % patients with dactylitis: INX = 34.0% vs Pbo = 11.8%. Change at 54 wks, % patients with dactylitis: INX = 14.8% vs Pbo = 12.2%	24, 54, wks	< 0.001 at 24 wks	N/A
Genovese²³	Multicenter (n = 16 sites) in US & Canada	DB-RPC	n = 100	ADM vs Pbo	Dactylitis scored 0 to 3	Mean change in dactylitis score at 12 wks: ADM = −2.4, Pbo = −1.4	12 wks	> 0.05	N/A
Healy²⁴	Single center in Britain	OL	n = 28	MTX (n = 19), LEF (n = 4), dactylitis HC (n = 1), ETN (n = 4)	LDI, LDI basic, scored 0–3, No. of dactylitic digits (tender /nontender), No. of dactylitic digits (tender)	Change at 6 mo: various treatments pooled, effect sizes reported	6 mo	N/A	LDI (0.99), LDI basic (0.9), dactylitis score (1.63), No. tender/nondactylitic digits (0.77), No. tender dactylitic digits (1.27)
Antoni (IMPACT 1)²⁵	Multicenter (n = 9 sites) in Europe, US, & Canada	DB-RPC	n = 104	INX vs Pbo	Dactylitis scored 0–3	Change at 16 wks (mean ± SD): INX = 1.94 ± 0.23, Pbo = 0.58 ± 0.20	16 wks	< 0.001	0.41
Antoni (IMPACT 2)²⁶	Multicenter (n = 36 sites) in Europe, US, & Canada	DB-RPC	n = 200	INX vs Pbo	% with dactylitis of hands/feet	Change at 14 wks (% reduction in patients with dactylitis): INX = −23, Pbo = −13	14 wks	0.025	N/A
Mease²⁷	Multicenter (n = 50 sites) in US, Canada, & Europe	DB-RPC	n = 249	ADM vs Pbo	Dactylitis scored 1–4	Results not provided. No statistical difference at 24 wks	24 wks	N/A	N/A
Kaltwasser (TOPAS)²⁸	Multicenter (n = 31 sites) in Australia, Europe, Canada, & New Zealand	DB-RPC	n = 186	LEF vs Pbo	Dactylitis scored 1 to 4	Mean ± SD change from baseline at 24 wks: LEF = −0.9 ± 2.7, Pbo = −0.2 ± 2.4	24 wks	0.2	0.33
Salvarani²⁹	Multicenter study in Europe	OL	n = 16	INX added to MTX	No. of dactylitic digits (tender)	Change at 30 wks: no dactylitis was observed during the study period	30 wks	N/A	N/A
Salvarani³⁰	Multicenter study in Europe	OL	n = 99	SSZ vs CyA vs ST	No. of dactylitic digits enough	Change at 24 wks: not data to be clinically meaningful [Only 4 subjects developed dactylitis (1 SSZ, 2 CyA, 1 ST)]	24 wks	N/A	N/A
Clegg³¹	Multicenter study of US Veterans	DB-RPC	n = 221	SSZ vs Pbo	No. of dactylitic digits (tender & nontender)	Mean ± SD change from baseline at 36 wks: SSZ = −0.5 ± 4.2, Pbo = −0.9 ± 4.1	36 wks	0.43	0.2

↵* Primary data for this analysis generously provided by Janssen Pharmaceuticals. DB-RPC: Double-blinded, randomized, placebo-controlled trial, OL: Open-label study, N/A: Not applicable, DMARD: Disease-modifying antirheumatic drug, SD: Standard deviation, SEM: Standard error of the mean, IQR: Interquartile range, LDI: Leeds Dactylitis Index; APR: Apremilast, CZP: Certolizumab, UST: Ustekinumab, Pbo: Placebo, GOL: Golimumab, ADM: Adalimumab, MTX: Methotrexate, INX: Infliximab, ETN: Etanercept, CyA: Cyclosporin A, ANA: Anakinra, HC: Hydroxychloroquine, LEF: Leflunomide, SSZ: Sulfasalazine, ST: Standard therapy.