Response to ibudilast treatment according to progressive multiple sclerosis disease phenotype.
Response to ibudilast treatment according to progressive multiple sclerosis disease phenotype.
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DOI：
10.1002/acn3.51251
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发表时间：
2021-01
影响因子：
5.3
通讯作者：
SPRINT-MS Investigators
中科院分区：
文献类型：
--
作者：
Goodman AD;Fedler JK;Yankey J;Klingner EA;Ecklund DJ;Goebel CV;Bermel RA;Chase M;Coffey CS;Klawiter EC;Naismith RT;Fox RJ;SPRINT-MS Investigators
确定原发性 (PPMS) 和继发性 (SPMS) 进行性多发性硬化症参与者之间异丁司特对脑萎缩率的治疗效果是否不同。 MS 的进展形式均与持续的残疾进展相关。 PPMS 和 SPMS 的治疗反应是否不同仍不清楚。 SPRINT-MS 是一项针对 PPMS (n = 134) 和 SPMS (n = 121) 患者的随机、安慰剂对照 96 周 2 期试验。通过拟合三向相互作用线性混合模型，检查了 PPMS 和 SPMS 表型对通过脑实质分数 (BPF) 测量的脑萎缩变化率的影响。探索了对基线人口统计、疾病测量和大脑大小差异的调整。分析表明时间、治疗效果和疾病表型之间存在三向交互作用（P < 0.06）。经过进一步检查，总体治疗效果主要由 PPMS 患者驱动（P < 0.01），而不是由 SPMS 患者驱动（P = 0.97）。这种差异可能是由于与 SPMS 安慰剂组相比，PPMS 安慰剂组的脑萎缩进展更快（P < 0.02）。尽管向后选择（P < 0.05）保留了年龄、T2 病变体积、RNFL 和纵向扩散率作为线性混合模型中的显着基线协变量，但调整后的总体治疗效果仍然由 PPMS 驱动（P < 0.01）。先前报道的异丁司特对进行性多发性硬化症脑萎缩恶化的总体治疗效果似乎是由 PPMS 患者驱动的，部分原因可能是安慰剂治疗组的萎缩进展速度更快。
Determine whether a treatment effect of ibudilast on brain atrophy rate differs between participants with primary (PPMS) and secondary (SPMS) progressive multiple sclerosis. Progressive forms of MS are both associated with continuous disability progression. Whether PPMS and SPMS differ in treatment response remains unknown. SPRINT‐MS was a randomized, placebo‐controlled 96‐week phase 2 trial in both PPMS (n = 134) and SPMS (n = 121) patients. The effect of PPMS and SPMS phenotype on the rate of change of brain atrophy measured by brain parenchymal fraction (BPF) was examined by fitting a three‐way interaction linear‐mixed model. Adjustment for differences in baseline demographics, disease measures, and brain size was explored. Analysis showed that there was a three‐way interaction between the time, treatment effect, and disease phenotype (P < 0.06). After further inspection, the overall treatment effect was primarily driven by patients with PPMS (P < 0.01), and not by patients with SPMS (P = 0.97). This difference may have been due to faster brain atrophy progression seen in the PPMS placebo group compared to SPMS placebo (P < 0.02). Although backward selection (P < 0.05) retained age, T2 lesion volume, RNFL, and longitudinal diffusivity as significant baseline covariates in the linear‐mixed model, the adjusted overall treatment effect was still driven by PPMS (P < 0.01). The previously reported overall treatment effect of ibudilast on worsening of brain atrophy in progressive MS appears to be driven by patients with PPMS that may be, in part, because of the faster atrophy progression rates seen in the placebo‐treated group.
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影响因子：
9.9
作者：
Lublin FD;Reingold SC;Cohen JA;Cutter GR;Sørensen PS;Thompson AJ;Wolinsky JS;Balcer LJ;Banwell B;Barkhof F;Bebo B Jr;Calabresi PA;Clanet M;Comi G;Fox RJ;Freedman MS;Goodman AD;Inglese M;Kappos L;Kieseier BC;Lincoln JA;Lubetzki C;Miller AE;Montalban X;O'Connor PW;Petkau J;Pozzilli C;Rudick RA;Sormani MP;Stüve O;Waubant E;Polman CH
通讯作者：
Polman CH
影响因子：
9.9
作者：
Barkhof, F.;Hulst, H. E.;Landin, R.
通讯作者：
Landin, R.
DOI：
10.1056/nejmoa1803583
发表时间：
2018-08-30
期刊：
The New England journal of medicine
影响因子：
--
作者：
Fox RJ;Coffey CS;Conwit R;Cudkowicz ME;Gleason T;Goodman A;Klawiter EC;Matsuda K;McGovern M;Naismith RT;Ashokkumar A;Barnes J;Ecklund D;Klingner E;Koepp M;Long JD;Natarajan S;Thornell B;Yankey J;Bermel RA;Debbins JP;Huang X;Jagodnik P;Lowe MJ;Nakamura K;Narayanan S;Sakaie KE;Thoomukuntla B;Zhou X;Krieger S;Alvarez E;Apperson M;Bashir K;Cohen BA;Coyle PK;Delgado S;Dewitt LD;Flores A;Giesser BS;Goldman MD;Jubelt B;Lava N;Lynch SG;Moses H;Ontaneda D;Perumal JS;Racke M;Repovic P;Riley CS;Severson C;Shinnar S;Suski V;Weinstock-Guttman B;Yadav V;Zabeti A;NN102/SPRINT-MS Trial Investigators
通讯作者：
NN102/SPRINT-MS Trial Investigators
影响因子：
11.2
作者：
Eshaghi A;Prados F;Brownlee WJ;Altmann DR;Tur C;Cardoso MJ;De Angelis F;van de Pavert SH;Cawley N;De Stefano N;Stromillo ML;Battaglini M;Ruggieri S;Gasperini C;Filippi M;Rocca MA;Rovira A;Sastre-Garriga J;Vrenken H;Leurs CE;Killestein J;Pirpamer L;Enzinger C;Ourselin S;Wheeler-Kingshott CAMG;Chard D;Thompson AJ;Alexander DC;Barkhof F;Ciccarelli O;MAGNIMS study group
通讯作者：
MAGNIMS study group
影响因子：
1.3
作者：
Smith, SM;De Stefano, N;Matthews, PM
通讯作者：
Matthews, PM