Rituximab is more effective than second anti-TNF therapy in rheumatoid arthritis patients and previous TNFα blocker failure

Figures & data

Table 1 Demographic and disease-related characteristics at start of documentation (baseline)

Characteristics	Rituximab n = 90	TNFα blocker n = 106
Gender, male (n [%])	24 (26.7)	20 (18.9)
Age, years (median [range])	57 (27–79)	58 (21–83)
Duration of disease at inclusion, years (median [range])	7.3 (0.9–30.6)	8.4 (0.2–38.3)
Seropositivity (n [%])
RF	67 (74.4)	89 (84.0)
Anti-CCP	68 (75.6)	64 (60.4)
RF or anti-CCP	79 (87.8)	91 (85.8)
RF and anti-CCP	56 (62.2)	62 (58.5)
Neither RF nor anti-CCP	10 (11.1)	13 (12.3)
Missing	1 (1.1)	2 (1.8)
DMARDs† (n [%])
Methotrexate	42 (46.7)	56 (52.8)
Leflunomide	26 (28.9)	28 (26.4)
Sulfasalazine	4 (4.4)	3 (2.8)
Antimalarials	1 (1.1)	3 (2.8)
Other DMARD	4 (4.4)	2 (1.9)
No DMARD	5 (5.6)	5 (4.7)
Missing	15 (16.7)	19 (17.9)
Oral glucocorticoids‡ (n [%])	79 (87.8)	88 (83.0)
Prior TNFα (n [%])
Etanercept	39 (43.3)	45 (42.5)
Adalimumab	43 (47.8)	42 (39.6)
Infliximab	5 (5.6)	18 (17.0)
Missing	3 (3.3)	1 (0.9)
C-reactive protein, mg/dL (mean ± SEM)	5.7 ± 0.9	4.8 ± 0.7
Erythrocyte sedimentation rate, mm/hour (m ± SEM)	36.4 ± 2.2	34.8 ± 2.2
DAS28 (m ± SEM)	5.6 ± 0.1	5.4 ± 0.1
Tender joint count (m ± SEM)	10.3 ± 0.7	8.9 ± 0.5
Swollen joint count (m ± SEM)	7.8 ± 0.6	7.2 ± 0.5
Health assessment questionnaire, total score (m ± SEM)	1.8 ± 0.1	1.6 ± 0.2

Notes:

† 7.6% of patients (rituximab: 5.5%, second tumor necrosis factor-α: 9.4%) were treated with combinations of disease-modifying antirheumatic drugs at baseline;

‡ median daily dose in methylprednisolone equivalent – rituximab group: 5 mg, tumor necrosis factor-α group: 7.5 mg.

Abbreviations: CCP, cyclic citrullinated peptide; DAS28, Disease Activity Score-28; DMARD, disease-modifying antirheumatic drug; RF, rheumatoid factor; SEM, standard error of mean; TNFα, tumor necrosis factor-α.

Figure 1 Change in mean disease activity score-28 values between endpoint and baseline in all patients and subgroups.

Abbreviations: CCP+, seropositive for cyclic citrullinated peptide; RF+, seropositive for rheumatoid factor; TNFα, tumor necrosis factor-α.

Table 2 Efficacy results depending on the first tumor necrosis factor-α inhibitor and seropositivity for rheumatoid factor and anti-cyclic citrullinated peptide: Disease Activity Score-28 change between baseline, 3 months, and 6 months

Previous TNFα	Subgroup	Month	Rituximab		TNFα		P value*
			n	Mean (95% CI)	n	Mean (95% CI)
Etanercept	All patients	3	28	−1.29 (−1.62; −0.96)	30	−0.76 (−1.06; −0.47)	0.017
		6	39	−1.53 (−1.98; −1.08)	45	−0.96 (−1.30; −0.62)	0.042
	RF+	3	22	−1.31 (−1.65; −0.96)	25	−0.72 (−1.06; −0.38)	0.016
		6	32	−1.54 (−2.04; −1.03)	37	−0.88 (−1.27; −0.50)	0.037
	Anti-CCP+	3	21	−1.23 (−1.59; −0.87)	19	−0.51 (−0.88; −0.13)	0.006
		6	31	−1.58 (−2.11; −1.05)	26	−0.81 (−1.29; −0.32)	0.035
	RF+ and anti-CCP+	3	18	−1.27 (−1.68; −0.87)	19	−0.51 (−0.88; −0.13)	0.006
		6	27	−1.56 (−2.12; −1.00)	26	−0.81 (−1.29; −0.32)	0.042
Adalimumab	All patients	3	35	−1.34 (−1.79; −0.90)	35	−1.21 (−1.66; −0.76)	0.673
		6	43	−1.70 (−2.10; −1.30)	42	−1.33 (−1.72; −0.93)	0.189
	RF+	3	24	−1.52 (−2.01; −1.04)	30	−1.12 (−1.63; −0.61)	0.252
		6	29	−1.78 (−2.27; −1.29)	37	−1.26 (−1.69; −0.82)	0.109
	Anti-CCP+	3	26	−1.64 (−2.18; −1.11)	21	−0.88 (−1.57; −0.19)	0.073
		6	33	−1.95 (−2.41; −1.50)	26	−1.08 (−1.49; −0.68)	0.006
	RF+ and anti-CCP+	3	21	−1.60 (−2.14; −1.05)	20	−0.77 (−1.45; −0.08)	0.053
		6	25	−1.86 (−2.42; −1.29)	25	−1.00 (−1.38; −0.62)	0.013
Infliximab	All patients	3	5	−1.17 (−2.30; −0.04)	13	−1.73 (−2.34; −1.13)	0.292
		6	5	−1.36 (−2.12; −0.60)	18	−1.53 (−2.11; −0.96)	0.756
	RF+	3	5	−1.17 (−2.30; −0.04)	10	−2.09 (−2.47; −1.72)	0.026
		6	4	−1.45 (−2.51; −0.39)	14	−1.82 (−2.32; −1.32)	0.440
	Anti-CCP+	3	4	−0.94 (−2.34; +0.45)	7	−1.99 (−2.42; −1.57)	0.026
		6	4	−1.45 (−2.51; −0.39)	11	−1.75 (−2.33; −1.17)	0.542
	RF+ and anti-CCP+	3	4	−0.94 (−2.34; +0.45)	7	−1.99 (−2.42; −1.57)	0.026
		6	4	−1.45 (−2.51; −0.39)	10	−1.74 (−2.39; −1.10)	0.570

Notes:

* P values associated with t-test for comparison of the two cohorts. All P values are descriptive information.

Abbreviations: CCP+, seropositive for cyclic citrullinated peptide; CI, confidence interval; RF+, seropositive for rheumatoid factor; TNFα, tumor necrosis factor-α.

Figure 2 The mean absolute values of erythrocyte sedimentation rate, tender joint counts, swollen joint counts, and pain visual analog scale at baseline, 3 months posttreatment, and 6 months posttreatment.

Note: The average percent improvement between baseline and 6 months posttreatment for rituximab cohort and tumor necrosis factor-α, respectively, are included in the legend section (change of group means).
Abbreviations: BL, baseline; ESR, erythrocyte sedimentation rate; M3, 3 months posttreatment; M6, 6 months posttreatment; SJC, swollen joint counts; TJC, tender joint counts; TNFα, tumor necrosis factor-α; VAS, visual analog scale.

Table 3 Efficacy results: change from baseline to end of observation (196 patients)

Efficacy variable	Rituximab		TNFα blocker		P value*
	n	Mean (95% CI)	n	Mean (95% CI)
DAS28
All patients	90	−1.64 (−1.92; −1.36)	106	−1.19 (−1.42; −0.96)	0.013
Seropositive for RF	67	−1.66 (−1.98; −1.34)	89	−1.17 (−1.43; −0.91)	0.018
Seropositive for CCP	68	−1.75 (−2.07; −1.43)	64	−1.06 (−1.34; −0.78)	0.002
Seropositive for RF and CCP	56	−1.69 (−2.05; −1.32)	62	−1.01 (−1.29; −0.73)	0.004
Not seropositive for RF or CCP	10	−1.07 (−2.08; −0.06)	13	−0.93 (−1.58; −0.28)	0.791
Tender joint count	89	−5.08 (−6.43; −3.73)	105	−3.66 (−4.60; −2.72)	0.088
Swollen joint count	89	−3.83 (−5.00; −2.67)	105	−3.19 (−4.13; −2.25)	0.390
Visual analog scale	86	−2.15 (−2.62; −1.67)	93	−1.99 (−2.49; −1.48)	0.646
Erythrocyte sedimentation rate, mm/hour	88	−10.51 (−14.85; −6.17)	103	−6.81 (−10.90; −2.72)	0.220
C-reactive protein, mg/dL	72	−2.37 (−3.98; −0.77)	83	−0.90 (−2.34; +0.55)	0.173
Health assessment questionnaire	26	−0.13 (−0.31; +0.05)	21	−0.29 (−0.52; −0.06)	0.257

Notes:

* P values associated with t-test for comparison of the two cohorts. All P values except for DAS28 “all patients” are descriptive information.

Abbreviations: CCP, cyclic citrullinated peptide; CI, confidence interval; DAS28, Disease Activity Score-28; RF, rheumatoid factor; TNFα, tumor necrosis factor-α.

Figure 3 European league against Rheumatism response at observation endpoint in all groups.

Abbreviations: CCP+, seropositive for cyclic citrullinated peptide; RF+, seropositive for rheumatoid factor; RTX, rituximab cohort; TNFa, tumor necrosis factor-α cohort.