Early response to certolizumab pegol predicts long-term outcomes in patients with active rheumatoid arthritis: results from the Japanese studies

Figures & data

Figure 1. Schematic of the study design of J-RAPID and HIKARI. (a) Patients with active rheumatoid arthritis despite treatment with MTX were randomly assigned to one of four groups, certolizumab pegol 100 mg, 200 mg, 400 mg with MTX or placebo with MTX. (b) Patients with active rheumatoid arthritis who cannot be treated with MTX were randomly assigned to certolizumab pegol 200 mg or placebo group. In both studies, patients withdrawn from the study due to lack of efficacy at week 16 or completed the study were enrolled into open-label extension study. Certolizumab pegol 200 mg group of both study were included in this analyses.

Figure 2. Proportion of patients achieving a ≥ 0.6 and a ≥ 1.2 change in DAS28(ESR) from baseline in patients with active rheumatoid arthritis treated with certolizumab pegol with or without MTX (full analysis set, LOCF). (a) J-RAPID study. Patients with inadequate response to MTX were treated with certolizumab pegol plus MTX. (b) HIKARI study. Patients who cannot be treated with MTX were treated with certolizumab pegol without concomitant MTX.

Figure 3. Percentage of patients in remission at year 1 by improvement in DAS28(ESR) at each time point in patients with active rheumatoid arthritis treated with certolizumab pegol with or without MTX. (a) J-RAPID - DAS28(ESR) of ≥ 1.2, (b) HIKARI - DAS28(ESR) of ≥ 1.2, (c) J-RAPID - DAS28(ESR) of ≥ 0.6, (d) HIKARI - DAS28(ESR) of ≥ 0.6.

Figure 4. Change in mTSS at year 1 by response at week 1, 6, and 12 in patients with active rheumatoid arthritis treated with certolizumab pegol with or without MTX. (a) J-RAPID - DAS28(ESR) of ≥ 1.2, (b) HIKARI - DAS28(ESR) of ≥ 1.2, (c) J-RAPID - DAS28(ESR) of ≥ 0.6, (d) HIKARI - DAS28(ESR) of ≥ 0.6.

Table 1. Proportions of radiographic non-progression and rapid-radiographic progression after 1 year treatment by response at week 1, 6, and 12 in patients with active rheumatoid arthritis treated with certolizumab pegol with or without MTX.

	Radiographic non-progression		Rapid radiographic progression
	Responder	Non-responder	Responder	Non-responder
J-RAPID ⊿DAS28 ≥ 1.2 at
Week 1	68.0% (17/25)	71.4% (40/56)	12.0% (3/25)	16.1% (9/56)
Week 6	73.8% (45/61)	60.0% (12/20)	13.1% (8/61)	20.0% (4/20)
Week 12	75.8% (47/62)	52.6% (10/19)	9.7% (6/62)	31.6% (6/19)
⊿DAS28 ≥ 0.6 at
Week 1	67.7% (42/62)	78.9% (15/19)	16.1% (10/62)	10.5% (2/19)
Week 6	71.4% (55/77)	50.0% (2/4)	14.3% (11/77)	25.0% (1/4)
Week 12	74.6% (53/71)	40.0% (4/10)	11.3% (63/71)	40.0% (4/10)
HIKARI ⊿DAS28 ≥ 1.2 at
Week 1	55.3% (21/38)	65.8% (50/76)	15.8% (6/38)	18.4% (14/76)
Week 6	66.7% (54/81)	51.5% (17/33)	13.6% (11/81)	27.3% (9/33)
Week 12	65.1% (56/86)	53.6% (15/28)	15.1% (13/86)	25.0% (7/28)
⊿DAS28 ≥ 0.6 at
Week 1	61.7% (50/81)	63.6% (21/33)	16.0% (13/81)	21.2% (7/33)
Week 6	64.4% (67/104)	40.0% (4/10)	15.4% (16/104)	40.0% (4/10)
Week 12	64.7% (66/102)	41.7% (5/12)	15.7% (66/102)	33.3% (4/12)

Each value represents the percentage of radiographic non-progression or Rapid radiographic progression (number of patients with non-progression or rapid progression/number of responder or non-responder at week 1, 6, or 12)

Table 2. Probability of low disease activity or remission after 1 year treatment by response at week 12 in patients with active rheumatoid arthritis treated with certolizumab pegol with or without MTX.

	Response at week 12
	⊿DAS28(ESR) ≥ 1.2	⊿DAS28(ESR) ≥ 0.6	CRP < 50% of baseline	DAS28(ESR)≤ 5.1	DAS28(ESR)≤ 3.2	DAS28(ESR)< 2.6	EULAR Good	EULAR Good or Moderate
J-RAPID (with MTX, n = 82)
Week 12 responder (responder/total)	76.8% (63/82)	87.8% (72/82)	75.6% (62/82)	79.3% (65/82)	28.0% (23/82)	15.9% (13/82)	28.0% (23/82)	84.1% (69/82)
LDA at year 1 in week 12 responder	54.0% (34/63)	51.4% (37/72)	58.1% (36/62)	52.3% (34/65)	78.3% (18/23)	84.6% (11/13)	78.3% (18/23)	52.2% (36/69)
LDA at year 1 in week 12 non-responder	21.1% (4/19)	10.0% (1/10)	10.0% (2/20)	23.5% (4/17)	33.9% (20/59)	39.1% (27/69)	33.9% (20/59)	15.4% (2/13)
Positive predictive value	0.540	0.514	0.581	0.523	0.783	0.846	0.783	0.522
Negative predictive value	0.789	0.900	0.900	0.765	0.661	0.609	0.661	0.846
Odds ratio (95% confidence limits)	4.40 (1.31–14.73)	9.51 (1.15–79.03)	12.46 (2.66–58.45)	3.56 (1.05–12.01)	7.02 (2.27–21.69)	8.56 (1.76–41.63)	7.02 (2.27–21.69)	6.00 (1.24–29.10)
Remission at year 1 in week 12 responder	41.3% (26/63)	37.5% (27/72)	41.9% (26/62)	38.5% (25/65)	65.2% (15/23)	76.9% (10/13)	65.2% (15/23)	37.7% (26/69)
Remission at year 1 in week 12 non-responder	5.3% (1/19)	0.0% (0/10)	5.0% (1/20)	11.8% (2/17)	20.3% (12/59)	24.6% (17/69)	20.3% (12/59)	7.7% (1/13)
Positive predictive value	0.413	0.375	0.419	0.385	0.652	0.769	0.652	0.377
Negative predictive value	0.947	1.000	0.950	0.882	0.797	0.754	0.797	0.923
Odds ratio (95% confidence limits)	12.65 (1.59–100.76)	NC	13.72 (1.73–109.09)	4.69 (0.99–22.26)	7.34 (2.53–21.34)	10.20 (2.51–41.41)	7.34 (2.53–21.34)	7.26 (0.89–59.09)
HIKARI (without MTX, n = 116)
Week 12 responder	74.1% (86/116)	88.8% (103/116)	63.8% (74/116)	74.1% (86/116)	24.1% (28/116)	13.8% (16/116)	24.1% (28/116)	81.0% (94/116)
LDA at year 1 in week 12 responder	48.8% (42/86)	46.6% (48/103)	45.9% (34/74)	51.2% (44/86)	71.4% (20/28)	75.0% (12/16)	71.4% (20/28)	47.6% (45/94)
LDA at year 1 in week 12 non-responder	20.0% (6/30)	0.0% (0/13) 0.466	33.3% (14/42)	13.3% (4/30)	31.8% (28/88)	36.0% (36/100)	31.8% (28/88)	13.6% (3/22)
Positive predictive value	0.488	0.466	0.459	0.512	0.714	0.750	0.714	0.479
Negative predictive value	0.800	1.000	0.667	0.867	0.682	0.640	0.682	0.864
Odds ratio (95% confidence limits)	3.82 (1.42–10.27)	NC	1.70 (0.77–3.74)	6.81 (2.19–21.17)	5.36 (2.10–13.64)	5.33 (1.60–17.76)	5.36 (2.10–13.64)	5.82 (1.61–20.99)
Remission at year 1 in week 12 responder	34.9% (30/86)	31.1% (32/103)	33.8% (25/74)	36.0% (31/86)	64.3% (18/28)	75.0% (12/16)	64.3% (18/28)	33.0% (31/94)
Remission at year 1 in week 12 non–responder	6.7% (2/30) 0.349	0.0% (0/13) 0.311	16.7% (7/42)	3.3% (1/30) 0.360	15.9% (14/88)	20.0% (20/100)	15.9% (14/88)	4.5% (1/22) 0.330
Positive predictive value	0.349	0.311	0.338	0.360	0.643	0.750	0.643	0.330
Negative predictive value	0.933	1.000	0.833	0.967	0.841	0.800	0.841	0.955
Odds ratio (95% confidence limits)	7.50 (1.67–33.66)	NC	2.55 (0.99–6.55)	16.35 (2.12–125.90)	9.51 (3.64–24.88)	12.00 (3.50–41.18)	9.51 (3.64–24.88)	10.33 (1.33–80.40)

Positive predictive value: number of patients who achieved low disease activity or remission in responder/number of responder; Negative predictive value: number of patients who did not achieve low disease activity or remission in non-responder/number of non-responder; NC not calculated.

Figure 5. Change in mTSS at year 1 by response at week 12 in patients with active rheumatoid arthritis treated with certolizumab pegol with or without MTX. (a) J-RAPID, (b) HIKARI.

Figure 6. Percentage of remission at year 1 by baseline characteristics in patients with or without response of DAS28(ESR) ≥ 1.2 at week 12. (a) J-RAPID, (b) HIKARI.

Figure 7. Percentage of LDA and remission rates and change in mTSS in patients with or without response of DAS28(ESR) ≥ 1.2 at week 12 in HIKARI patients treated with or without non-MTX DMARDs.