OPTIRRA研究：
TNF拮抗剂维持期优化减量方案
SAT0150
OPTIMISING TREATMENT
WITH TNF INHIBITORS IN RHEUMATOID ARTHRITIS WITH DIFFERENT DOSE
TAPERING STRATEGIES: THE OPTTIRA TRIAL
J. B.
Galloway1,2,*, G. Kingsley1, M. Ma2,3, B. Lorente-Canovas4,
A. Cope3, F. Ibrahim3, D. L. Scott2,3
1Academic
Rheumatology, King’s
College London, 2Rheumatology, King's College Hospital
NHS Foundation Trust, 3Academic Rheumatology, King's
College London, 4Academic Rheumatology, Kings's College
London, London, United Kingdom
|
Background: Treating
rheumatoid arthritis (RA) with tumour necrosis factor inhibitors
(TNFi) involves inducing then maintaining responses. Currently both
use identical TNFi dosing regimens.
|
背景：TNF拮抗剂( TNF拮抗剂
)治疗RA包括包括诱导期和维持期，目前两期均使用相同剂量。
|
|
Objectives: OPTTIRA,
a pragmatic, multicentre, 12-month randomised controlled trial,
evaluated if tapering TNFi doses causes loss of
response.
|
目的：OPTTIRA试验为多中心随机对照研究，为期12个月，旨在通过比较不同治疗范式，评价TNF拮抗剂减量是否能维持疗效。
|
|
Methods: We
recruited RA patients receiving etanercept or adalimumab plus a
DMARD with stable low disease activity (DAS28 less than 3.2 for
over 3 months). We excluded patients with serious concomitant
illness or taking high-dose steroids (more than 10mg prednisolone
daily). Initially (months 0-6) patients were randomised to three
groups: controls received constant TNFis; one experimental group
tapered TNFis by 33% and the other by 66%. If tapering caused
flares (increase in DAS28 more than or equal to 0.6 plus 1 or more
swollen joints out of 66 joints) TNFis were restarted. Subsequently
(months 6-12) controls tapered TNFis and experimental groups
discontinued TNFis. The outcomes comprised flare rates and DAS28
scores after 6 months constant or tapered TNFis.
|
方法：招募接受依那西普或或阿达木单抗联合一种DMARD治疗达到稳定低疾病活动度的RA患者(维持DAS28＜3.2至少3个月)。排除有严重并发症的患者或使用高剂量糖皮质激素的患者(＞10
mg/d
)。患者入组后随机分为3组治疗6个月，对照组接受足剂量TNF拮抗剂治疗，两个TNF拮抗剂减量组，其一减量33%，另一减量66%。如果减量导致复发(
DSA28增加≥0.6，且66个目标关节的肿胀关节计数≥1
)，则重启足剂量TNF拮抗剂治疗。在后续6个月里，原足剂量组(对照组)将TNF拮抗剂减量，两支原减量组(试验组)停用TNF拮抗剂。研究终点为比较6个月接受TNF拮抗剂足量或减量治疗患者的复发率及DAS28改变。
|
|
Results: 227
patients were screened at 20 UK centres, 103 were randomized, 97
were treated in months 0-6 and 74 in months 6-12.
With TNFis
tapering: flares occurred in 14% of controls,
13% patients tapered by one-third and 37% tapered by two-thirds.
Flares were increased with two-thirds tapering with odds ratio 4.1;
95% (CI 1.3, 14.5) compared with one-third tapering. Post-tapering
flares resolved when TNFis were restarted. There were no
significant differences in HAQ with either tapering strategy
(Table) at six months. Of 47 patients who tapered then stopped
TNFis. 21/47 (45%) succeeded without flaring and their final mean
DAS28 scores after stopping treatment were 2.2 (95% CI 1.6, 2.9).
Evaluating harms showed one patient withdrew for TNFis-related
toxicity (control) and four patients had serious adverse events
(control 1; experimental 3); none were related to TNFis
tapering.
|
结果：筛选来自英国20个中心共227例RA患者，103例患者随机分组，97例完成头6个月试验，74例患者完成全部12个月随访。TNF拮抗剂减量复发情况：对照组14%，1/3减量组13%，2/3减量组37%。减量2/3组的复发高于减量1/3组,
比值比为4.1 (95%CI：1.3-14.5
)。重启足剂量治疗可在减量复发后迅速控制病情。不同减量策略治疗6个月对HAQ的影响无明显差异(
详见下表
)。共有47例患者减量后停药，其中45%(21/47)的患者随访至第12月时仍无复发，他们停药后的末次随访DSA28均值为2.2
(95%CI:
1.6-2.9)。药物安全性如下，1例患者因药物相关毒性退出试验(
对照组 )，4例患者发生严重不良事件(
1例对照组，试验组3例
)，均与TNF拮抗剂减量无关。
|
|
Conclusions: Good
responses to TNFi are maintained after TNFi doses are tapered by
one-third. Tapering by two-thirds results in more flares, but these
respond to restarting TNFis and did not adversely affect disability
progression. Some patients maintain responses after stopping TNFis.
Lowering TNFi maintenance doses retains responses at substantially
reduced drug costs. Adopting this strategy should enhance biologic
cost-effectiveness.
|
结论：TNF拮抗剂减量1/3良好地维持了临床疗效。减量2/3的复发率升高，但重新接受足量治疗后疗效仍佳，未见关节功能残障进展。一些患者停用TNF拮抗剂后疾病仍控制良好。降低TNF拮抗剂维持期剂量既能维持临床疗效又可大大降低药物花费。使用这种策略可提升生物制剂的成本-效益。
|
|
|
对照组
|
33% 减量
|
66% 减量
|
|
病例数
|
50
|
48
|
38
|
|
复发率
(%)
|
7
(14%)
|
6
(13%)
|
14
(37%)
|
|
6个月治疗后的平均 DAS28 (95%
CI)
|
2.2
(1.9, 2.4)
|
2.1
(1.9, 2.3)
|
2.0
(1.6, 2.3)
|
|
6个月治疗后的平均HAQ (95%
CI)
|
0.73
(0.51, 0.96)*
|
0.78
(0.56,0.99)
|
0.72
(0.44,1.0)
|
|