Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose: To determine the optimal treatment strategy in patients with anti-citrullinated protein antibodies (ACPA) negative (‒) rheumatoid arthritis (RA), as it has been suggested that these patients require a different treatment approach than ACPA positive (+)patients.
Methods: 184 ACPA‒ patients were randomized to 1. sequential monotherapy, 2. step-up therapy, 3. initial combination with prednisone, 4. initial combination with infliximab, as were 300 ACPA+ patients. Treatment adjustments were based on 3-monthly disease activity score (DAS) measurements, aiming at DAS ≤2.4. Functional ability (health assessment questionnaire, HAQ), radiographic progression (Sharp van der Heijde score, SHS) and (drug-free) remission (DAS <1.6) percentages over 10 years were compared between the 4 arms in ACPA‒ patients and between ACPA‒ and ACPA+ patients per randomisation arm.
Results: At 3 months, ACPA‒ patients achieved more often DAS ≤2.4 (52% versus 18%, p<0.001), remission (17% vs 5%, p<0.001) and improvement in functioning (mean HAQ 0.6 vs 1.0, p<0.001) on initial combination therapy than on initial monotherapy. These differences remained until year 1. After 10 years of targeted therapy, over time no differences were retrieved (p=0.551 for HAQ, p=0.851 for remission). Table 1 shows the main outcomes at year 10.
Drug survival (achieve and maintain DAS ≤2.4) on methotrexate monotherapy (1st step in arm 1 and 2) was similar in ACPA‒ and ACPA+ patients (median survival 10 vs 7 months, p=0.750), as also drug survival on sulphasalazine (2nd step in arm 1 and 2, median survival 3 vs 3 months, p=0.659). At year 1, in arm 3 18/55 ACPA‒ (33%) and 31/68 ACPA+ patients (46%) tapered to monotherapy (p=0.310). In arm 4, 17/43 ACPA‒ (40%) and 38/82 ACPA+ patients (46%) discontinued infliximab (p=0.466).
Drug-free remission (DFR) was more often achieved and longer sustained in ACPA‒ than in ACPA+ patients, in all treatment arms (26% vs 8% in arm 1, p=0.077; 24% vs 9% in arm 2, p=0.048; 30% vs 2% in arm 3, p=0.002; 28% vs 6% in arm 4, p<0.001, median DFR duration averaged in 4 arms 69 vs 32 months, p=0.073). Over time, radiographic progression (Δ≥0.5 in SHS) in ACPA‒ patients was not different between the 4 arms (p=0.082). SHS progression was more often observed in ACPA+ patients than in ACPA‒patients in arm 1, 2 (both p<0.001) and arm 3 (p=0.016), but not in arm 4 (p=0.849).
Conclusion: On the short term, patients with ACPA‒ RA benefit more from initial combination therapy with prednisone or infliximab than from monotherapy, as also ACPA+ patients. During subsequent DAS steered therapy, ACPA‒ patients respond similarly to treatment steps in all 4 treatment arms to ACPA+ patients, suggesting that both groups require a similar treatment approach. After 10 years of targeted therapy, ACPA‒ patients achieve more often sustained drug-free remission than ACPA positive patients and show less radiographic progression, except in arm 4.
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Table 1: Main outcomes at year 10 for ACPA negative patients in the four treatment arms |
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Sequential monotherapy
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Step-up therapy
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Initial combination with prednisone
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Initial combination with infliximab
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p value
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|
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N = 40 |
N = 45 |
N = 56 |
N = 43 |
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Drop out, n (%) |
14 (35) |
20 (44) |
21 (38) |
16 (37) |
0.738 |
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DAS, mean ± SD |
1.7 ± 0.9 |
1.8 ± 0.8 |
1.6 ± 0.8 |
1.4 ± 0.8 |
0.431 |
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HAQ, mean ± SD |
0.5 ± 0.5 |
0.7 ± 0.7 |
0.5 ± 0.5 |
0.5 ± 0.5 |
0.580 |
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DAS-remission, n (%) |
11 (46) |
9 (41) |
17 (49) |
17 (63) |
0.434 |
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Drug-free remission, n (%) |
7 (26) |
7 (24) |
11 (30) |
9 (28) |
0.742 |
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On initial treatment step, n (%) |
10 (39) |
7 (28) |
18 (51) |
15 (56) |
0.161 |
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Use of infliximab, n (%) |
3 (12) |
3 (12) |
4 (11) |
4 (15) |
0.978 |
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Use of prednisone, n (%) |
0 (0) |
0 (0) |
3 (9) |
2 (7) |
0.226 |
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SHS progression, year 0-10, median (IQR) |
0.3 (0 – 1.4) |
0 (0 – 6.3) |
1.0 (0 – 5.3) |
0 (0 – 1.3) |
0.639 |
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SHS progression ≥5, n (%) |
1 (4) |
5 (24) |
8 (28) |
3 (14) |
0.132 |
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SHS progression ≥10, n (%) |
1 (4) |
3 (14) |
5 (17) |
1 (5) |
0.324 |
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Total AE, n* |
293 |
292 |
368 |
312 |
0.872 |
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Patients with AE, n (%) |
36 |
39 |
55 |
41 |
0.113 |
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Total SAE, n* |
50 |
33 |
60 |
43 |
0.183 |
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Patients with SAE, n (%) |
25 (63) |
19 (42) |
27 (48) |
22 (51) |
0.300 |
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Patients with serious infection, n (%) |
9 (23) |
5 (11) |
5 (9) |
3 (7) |
0.124 |
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Patients with malignancy, n (%) |
3 (8) |
2 (4) |
8 (14) |
6 (14) |
0.310 |
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Deceased, n |
1 |
4 |
1 |
4 |
0.220 |
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ACPA, anti-citrullinated protein antibodies; AE, adverse event; DAS: disease activity score; HAQ: health assessment questionnaire (scale 0-3);IQR, interquartile range; SAE, severe adverse event; SHS, Sharp van der Heijde score; SD, standard deviation.
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*More events per patient possible |
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Disclosure:
I. M. Markusse,
None;
G. Akdemir,
None;
L. Dirven,
None;
M. van den Broek,
None;
K. H. Han,
None;
H. K. Ronday,
None;
P. J. S. M. Kerstens,
None;
W. F. Lems,
None;
T. W. J. Huizinga,
None;
C. F. Allaart,
None.
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