Early radiological progression remains associated with long-term joint damage in real-world rheumatoid arthritis patients treated to the target of remission

Figures & data

Table 1. Baseline characteristics of the patients (n = 219)

Gender, female	139 (63.5)
Age (years)	57.4 ± 14.5
BMI (kg/m^2) (n = 210)	26.4 ± 4.6
Symptom duration (weeks)	13.0 (8.0–26.0)
RF positive	134 (61.2)
Anti-CCP positive	126 (57.5)
Fulfilling ACR 1987 criteria	170 (77.6)
DAS28	4.9 ± 1.1
TJC28	5.0 (2.0–10.0)
SJC28	8.0 (4.0–12.0)
ESR (mm/h)	28.0 (16.0–42.0)
CRP (mg/L)	12.0 (5.0–28.8)
Patient’s assessment of general health (0–100 VAS)	50.0 (30.0–66.0)
Erosive disease	35 (16.0)
SHS total	2.0 (0.0–6.0)
SHS erosion	0.0 (0.0–2.0)
SHS JSN	1.0 (0.0–4.0)

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

Except where indicated otherwise, values concern the total number of patients included.

BMI, body mass index; RF, rheumatoid factor; anti-CCP, anti-cyclic citrullinated peptide; ACR, American College of Rheumatology; DAS28, Disease Activity Score based on 28-joint count; TJC28, tender joint count including 28 joints; SJC28, swollen joint count including 28 joints; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; VAS, visual analogue scale; SHS, Sharp/van der Heijde score; JSN, joint space narrowing.

Table 2. Radiological outcomes over 6 years of follow-up

	Baseline	6 months	1 year	3 years	6 years
Available DAS28, n	219	219	215	197	142
Available SHS, n	219	192	210	200	129
Erosive disease*, n	35	55	74	97	89
Erosive disease cumulative, n	35	62	78	103	126
Erosion score, median (IQR)	0.0 (0.0–2.0)	1.0 (0.0–4.0)	2.0 (0.0–4.3)	3.0 (1.0–7.0)	4.0 (2.0–10.0)
JSN score, median (IQR)	1.0 (0.0–4.0)	1.0 (0.0–5.0)	2.0 (0.0–6.0)	3.0 (1.0–8.0)	5.0 (2.0–11.5)
Total SHS, median (IQR)	2.0 (0.0–6.0)	3.0 (1.0–8.0)	5.0 (2.0–10.0)	7.0 (3.0–15.0)	12.0 (6.0–22.0)
Total SHS, mean (95% CI)†	4.7 (3.8–5.8)	6.8 (5.5–8.4)	8.1 (6.5–10.0)	10.9 (8.8–13.5)	15.0 (12.1–18.6)

All change scores p < 0.001. *Only patients with available SHS data. †Estimated marginal mean SHS values using a linear mixed model.

DAS28, Disease Activity Score based on 28-joint count; SHS, Sharp/van der Heijde score; IQR, interquartile range; JSN, joint space narrowing; CI, confidence interval.

Figure 1. Probability plot of change from baseline in Sharp/van der Heijde score (SHS) at 6 years.

Table 3. Univariate negative binomial generalized linear mixed model (GLMM) for radiological progression (change from baseline) at 6 month, 1 year, 3 year, and 6 year follow-up

	Estimate	se	t	IRR	95% CI	p
Age	0.010	0.007	1.531	1.010	0.997–1.023	0.126
Gender, female	0.134	0.196	0.683	1.143	0.778–1.678	0.495
BMI	−0.005	0.021	−0.213	0.995	0.955–1.038	0.831
Symptom duration > 6 weeks	0.069	0.250	0.275	1.071	0.655–1.751	0.784
Anti-CCP positive	0.495	0.184	2.692	1.641	1.143–2.355	0.007
RF positive	0.011	0.196	0.057	1.011	0.688–1.487	0.955
DAS28	0.083	0.086	0.964	1.087	0.918–1.286	0.335
TJC28	−0.008	0.017	−0.444	0.992	0.960–1.026	0.657
SJC28	0.025	0.016	1.546	1.026	0.993–6.052	0.123
ESR	0.009	0.005	1.883	1.009	1.000–1.018	0.060
CRP	0.009	0.004	2.330	1.009	1.001–1.017	0.020
VAS general health	−0.005	0.004	−1.158	0.995	0.988–1.003	0.247
SHS total baseline	0.049	0.009	5.773	1.050	1.033–1.068	< 0.001
SHS erosion baseline	0.101	0.016	6.373	1.107	1.073–1.142	< 0.001
SHS JSN baseline	0.057	0.015	3.775	1.058	1.028–1.090	< 0.001
Baseline erosive disease	1.127	0.201	5.601	3.088	2.080–4.584	< 0.001
RRP (ΔSHS ≥ 4 after 6 months	1.439	0.187	7.771	4.217	2.923–6.083	< 0.001
DAS28 remission < 3 months	−0.105	0.210	−0.499	0.901	0.597–1.359	0.618
DAS28 remission < 6 months	−0.100	0.231	−0.431	0.905	0.575–1.425	0.667
Biological use during follow-up	0.200	0.236	0.847	1.221	0.768–1.941	0.397

IRR, incidence rate ratio; CI, confidence interval; BMI, body mass index; anti-CCP, anti-cyclic citrullinated peptide; RF, rheumatoid factor; DAS28, Disease Activity Score based on 28-joint count; TJC28, tender joint count including 28 joints; SJC28, swollen joint count including 28 joints; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; VAS, visual analogue scale; SHS, Sharp/van der Heijde score; JSN, joint space narrowing; RRP, rapid radiological progression.

Table 4. Multivariable negative binomial generalized linear mixed model (GLMM) for radiological progression (change from baseline) at 6 month, 1 year, 3 year, and 6 year follow-up

	Estimate	se	t	IRR	95% CI	p
Anti-CCP positive	0.353	0.159	2.226	1.424	1.043–1.944	0.026
CRP	0.003	0.003	0.859	1.003	0.997–1.009	0.391
Baseline erosive disease	0.473	0.228	2.070	1.604	1.025–2.551	0.024
RRP (ΔSHS ≥ 4 after 6 months	1.187	0.203	5.845	3.276	2.199–4.880	< 0.001

IRR, incidence rate ratio; CI, confidence interval; anti-CCP, anti-cyclic citrullinated peptide; RRP, rapid radiological progression; SHS, Sharp/van der Heijde score.

Table 5. Univariate logistic regression for rapid radiological progression (RRP)

	SHS ≥ 4 after 6 months (36/192)			SHS ≥ 6 after 6 months (21/192)
	OR	95% CI	p	OR	95% CI	p
Age	1.028	1.001–1.056	0.039	1.015	0.983–1.048	0.351
Gender	0.852	0.407–1.780	0.669	1.650	0.610–4.646	0.324
BMI	0.962	0.888–1.042	0.342	1.002	0.902–1.112	0.978
Symptom duration > 6 weeks	0.545	0.228–1.303	0.172	0.469	0.167–1.316	0.15
Anti-CCP positive	1.196	0.566–2.529	0.639	1.626	0.624–4.238	0.32
RF positive	0.625	0.302–1.295	0.206	0.902	0.361–2.256	0.825
DAS28	1.166	0.845–1.608	0.349	1.166	0.781–1.739	0.452
TJC28	0.993	0.930–1.060	0.835	0.935	0.845–1.034	0.188
SJC28	1.081	1.020–1.145	0.009	1.063	0.991–1.140	0.09
ESR	1.014	0.997–1.032	0.114	1.026	1.006–1.047	0.012
CRP	1.022	1.008–1.036	0.002	1.015	0.999–1.030	0.064
VAS general health	0.995	0.980–1.011	0.531	0.991	0.972–1.011	0.376
Baseline erosive disease	9.600	3.972–23.205	< 0.001	6.000	2.236–16.101	< 0.001
DAS28 remission < 3 months	0.467	0.198–1.097	0.08	0.394	0.126–1.230	0.109
DAS28 remission < 6 months	1.490	0.652–3.406	0.344	1.132	0.389–3.293	0.82

SHS, Sharp/van der Heijde score; OR, odds ratio; CI, confidence interval; BMI, body mass index; anti-CCP, anti-cyclic citrullinated peptide; RF, rheumatoid factor; DAS28, Disease Activity Score based on 28-joint count; TJC28, tender joint count including 28 joints; SJC28, swollen joint count including 28 joints; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; VAS, visual analogue scale.

Table 6. Multivariable logistic regression for rapid radiological progression (RRP)

	SHS ≥ 4 after 6 months			SHS ≥ 6 after 6 months
	OR	95% CI	p	OR	95% CI	p
Age	1.010	0.978–1.042	0.551	n/a	n/a	n/a
SJC28	1.048	0.979–1.123	0.179	1.038	0.958–1.125	0.36
CRP	1.017	1.001–1.033	0.037	0.996	0.973–1.019	0.729
ESR	n/a	n/a	n/a	1.026	0.996–1.056	0.087
Baseline erosive disease	8.773	3.328–23.128	< 0.001	5.215	1.871–14.536	0.002
DAS28 remission < 3 months	0.479	0.180–1.278	0.142	n/a	n/a	n/a
	Nagelkerke’s R^2 = 0.287			Nagelkerke’s R^2 = 0.170

SHS, Sharp/van der Heijde score; OR, odds ratio; CI, confidence interval; SJC28, swollen joint count including 28 joints; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; DAS28, Disease Activity Score based on 28-joint count; n/a, not applicable.

Figure 2. Course of median Sharp/van der Heijde score (SHS) over time plotted separately for each group. Lines are logarithmic fits to the data. The number of patients represents only the patients with available radiological data at all three time-points (baseline, 6 months, and 6 years). Number of total patients = 117 (the difference from 129 available SHS at 6 years in Table 2 is explained by the exclusion of patients with available SHS at 6 years, but missing SHS at 6 months). Number of patients with rapid radiological progression (RRP) = 27 (the difference from 36 in Table 4 is explained by exclusion of patients with available SHS at 6 months, but missing SHS at 6 years). RRP is defined as increase in SHS ≥ 4 after 6 months; nErosive, non-erosive at baseline; nRRP, non-rapid radiological progression.

Data availability statement

The data sets generated and/or analysed during the current study are not publicly available for legal and ethical reasons but are available from the corresponding author on reasonable request.