Serum golimumab concentration and anti-drug antibodies are associated with treatment response and drug survival in patients with inflammatory joint diseases: data from the NOR-DMARD study

Figures & data

Figure 1. Overview of the study population. axSpA, axial spondyloarthritis; RA, rheumatoid arthritis; PsA, psoriatic arthritis; ADAb, anti-drug antibodies; DAS28, 28-joint Disease Activity Score; DAPSA28, 28-joint Disease Activity index for PSoriatic Arthritis; NOCB, next observation carried backwards; LOCF, last observation carried forward

Table 1. Comparison of baseline characteristics in patients with golimumab serum concentration < 1.0 mg/L vs ≥ 1.0 mg/L at 3 month follow-up

	All	Golimumab < 1.0 mg/L	Golimumab ≥ 1.0 mg/L	p
Axial spondyloarthritis	(n = 47)	(n = 8)	(n = 39)
Age (years)	40 ± 11	41 ± 8	40 ± 12	0.81
Female	24 (51)	4 (50)	20 (51)	0.95
Disease duration (years)*	2.2 (0.5–8.9)	0.7 (0.4–5.6)	2.7 (1.0–20.9)	0.29
ASDAS-CRP	2.7 ± 1.0	2.4 ± 0.5	2.7 ± 1.1	0.41
HLA-B27 positive†	35 (88)	6 (75)	29 (91)	0.23
Prior use of bDMARD	26 (55)	5 (63)	21 (54)	0.65
Concomitant csDMARD	4 (9)	1 (13)	3 (8)	0.66
Rheumatoid arthritis	(n = 25)	(n = 10)	(n = 15)
Age (years)	52 ± 16	41 ± 18	59 ± 11	0.02
Female	22 (88)	9 (90)	13 (87)	0.80
Disease duration (years)‡	12.2 (4.9–25.6)	7.7 (3.8–25.8)	14.0 (5.3–25.5)	0.75
DAS28	4.6 ± 1.7	4.8 ± 1.6	4.4 ± 1.8	0.57
RF-positive§	13 (62)	7 (78)	6 (50)	0.20
Anti-CCP positive||	14 (67)	8 (89)	6 (50)	0.06
Prior use of bDMARD	20 (80)	8 (80)	12 (80)	1.00
Concomitant csDMARD	19 (76)	7 (70)	12 (80)	0.57
Psoriatic arthritis	(n = 35)	(n = 6)	(n = 29)
Age (years)	48 ± 12	50 ± 3	47 ± 13	0.33
Female	18 (51)	3 (50)	15 (52)	0.94
Disease duration (years)¶	5.0 (0.4–10.4)	7.4**	4.9 (0.4–11.3)	0.81
DAPSA28	13.4 (9.5–16.6)	15.3 (10.1–19.5)	13.0 (9.5–15.7)	0.52
Prior use of bDMARD	16 (47)	2 (33)	14 (50)	0.46
Concomitant csDMARD	22 (65)	3 (50)	19 (68)	0.41

Data are shown as mean ± sd, n (%), or median (interquartile range).

Data available in n = *28, †40, ‡14, §21, ||21, and ¶22 patients.

**Interquartile range not applicable, data available in n = 3 patients.

ASDAS-CRP, Ankylosing Spondylitis Disease Activity Score–C-reactive protein; HLA, human leucocyte antigen; bDMARD, biological disease-modifying anti-rheumatic drug; csDMARD, conventional synthetic disease-modifying anti-rheumatic drug; DAS28, 28-joint Disease Activity Score; RF, rheumatoid factor; anti-CCP, anti-cyclic citrullinated peptide; DAPSA28, 28-joint Disease Activity Index for PSoriatic Arthritis.

Figure 2. Distribution of golimumab serum concentrations in mg/L at 3 months (total inflammatory joint disease population). Median (interquartile range) = 2.2 (1.0–3.5) mg/L

Table 2. Response* (%) at 3 and 6 months, stratified by golimumab concentration at 3 months

	Overall	Golimumab < 1.0 mg/L§	Golimumab 1.0–3.9 mg/L||	Golimumab ≥ 4.0 mg/L¶	OR† (95% CI) response in golimumab ≥ 1.0 vs < 1.0 mg/L	p	OR‡ (95% CI) response in golimumab ≥ 4.0 vs 1.0–3.9 mg/L	p
Responders* after 3 months
All patients (n = 90)	47%	19%	49%	74%	5.8 (1.7–19.7)	0.005	2.1 (0.6–7.1)	0.24
axSpA (n = 41)	51%	14%	48%	82%	8.9 (0.8–102.2)	0.08	2.6 (0.3–20.6)	0.37
RA (n = 20)	55%	22%	78%	100% (n = 2)	26.5 (1.2–607.7)	0.04	NA**
PsA (n = 30)	37%	20%	37%	50%	2.8 (0.2–31.8)	0.40	1.3 (0.2–10.6)	0.83
bDMARD naïve (n = 40)	60%	13%	63%	85%	21.6 (2.0–233.5)	0.01	5.4 (1.0–30.4)	0.05
Responders* after 6 months
All patients (n = 90)	48%	33%	47%	68%	2.7 (0.9–7.8)	0.08	1.5 (0.4–5.1)	0.54
axSpA (n = 41)	56%	29%	52%	82%	3.9 (0.6–26.9)	0.17	2.5 (0.3–25.0)	0.42
RA (n = 20)	50%	44%	56%	50% (n = 2)	2.0 (0.2–18.7)	0.55	NA**
PsA (n = 30)	37%	20%	37%	50%	2.6 (0.2–30.2)	0.45	1.2 (0.1–11.8)	0.86
bDMARD naïve (n = 40)	60%	13%	63%	85%	26.4 (2.0–341.1)	0.01	5.6 (0.9–34.3)	0.06

*Response in axial spondyloarthritis (axSpA) was defined by clinically important improvement in the Ankylosing Spondylitis Disease Activity Score, in rheumatoid arthritis (RA) as European League Against Rheumatism good/moderate response, and in psoriatic arthritis (PsA) as improvement of ≥ 50% in the 28-joint Disease Activity Index for PSoriatic Arthritis (DAPSA28).

†/‡ Multivariable logistic regression comparing response in patients with golimumab † ≥ 1.0 vs < 1.0 mg/L and ‡ ≥ 4.0 vs 1.0–3.9 mg/L, adjusting for age, gender, and prior biological disease-modifying anti-rheumatic drug (bDMARD) use (Yes/No).

§n = 21 overall, 7 axSpA, 9 RA, 5 PsA, and 8 bDMARD naïve; ||n = 51 overall, 23 axSpA, 9 RA, 19 PsA, and 19 bDMARD naïve; ¶n = 19 overall, 11 axSpA, 2 RA, 6 PsA, and 13 bDMARD naïve.

**Odds ratio not applicable, data available in n = 2 patients.

OR, odds ratio; CI, confidence interval.

Figure 3. Proportion of responders at 3 months, stratified by golimumab concentration (mg/L). (A) Total inflammatory joint disease population; (B) Ankylosing Spondylitis Disease Activity Score (ASDAS) clinically important improvement (CII) responders in axial spondyloarthritis (AxSpA); (C) European League Against Rheumatism (EULAR) good/moderate response in rheumatoid arthritis (RA); (D) 28-joint Disease Activity Index for PSoriatic Arthritis (DAPSA28) ≥ 50% improvement in psoriatic arthritis (PsA)

Figure 4. Drug survival in patients with golimumab concentration < 1.0, 1.0–3.9, and ≥ 4.0 mg/L