Kay Jonathan, Fleischmann Roy, Keystone Edward, Hsia Elizabeth C, Hsu Benjamin, Mack Michael, Goldstein Neil, Braun Jürgen, Kavanaugh Arthur
Division of Rheumatology, Department of Medicine, University of Massachusetts Medical School and UMass Memorial Medical Center, Worcester, Massachusetts, USA.
Department of Rheumatology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Ann Rheum Dis. 2015 Mar;74(3):538-46. doi: 10.1136/annrheumdis-2013-204195. Epub 2013 Dec 16.
To assess pooled golimumab safety up to year 3 of rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) trials.
Golimumab 50 and 100 mg, administered subcutaneously (SC) every 4 weeks (q4wk), were assessed in patients with active RA (methotrexate-naïve, methotrexate-experienced and anti-TNF (tumour necrosis factor)-experienced), PsA or AS, despite conventional therapy. Placebo control continued up to week (wk) 24 (wk 52, methotrexate-naïve), with early escape at wk 16 (wk 28, methotrexate-naïve); subsequently, all patients received golimumab 50 or 100 mg q4wk. After the blinded controlled period, golimumab doses could be adjusted per investigator discretion. Pooled safety analyses reported herein include data from placebo-controlled and uncontrolled study periods up to wk 160. Determinations of incidences/100 patient-years (pt-yrs) for rare events also included RA patients from a phase IIb trial.
Across five phase III trials of SC golimumab, 639 patients received placebo and 2226 received golimumab 50 mg (n=1249) and/or 100 mg (n=1501) up to wk 160 (patients may be included in more than one group because non-responders were allowed early escape); 1179 patients were treated for ≥156 weeks. For placebo, golimumab 50 mg and golimumab 100 mg, respective adverse event incidences/100 pt-yrs (95% CIs) up to wk 160 were: 0.28 (0.01 to 1.56), 0.30 (0.12 to 0.62), 0.41 (0.23 to 0.69) for death; 5.31 (3.20 to 8.30), 3.03 (2.36 to 3.82), 5.09 (4.36 to 5.90) for serious infection; 0.00 (0.00 to 0.84), 0.17 (0.05 to 0.44), 0.35 (0.18 to 0.62) for tuberculosis; 0.00 (0.00 to 0.84), 0.13 (0.03 to 0.38), 0.24 (0.10 to 0.46) for opportunistic infection; 0.00 (0.00 to 0.84), 0.00 (0.00 to 0.13), 0.12 (0.03 to 0.30) for demyelination; and 0.00 (0.00 to 0.84), 0.04 (0.00 to 0.24), 0.18 (0.06 to 0.38) for lymphoma.
SC golimumab safety up to 3 years remained consistent with that of other TNF antagonists. Golimumab 100 mg showed numerically higher incidences of serious infections, demyelinating events and lymphoma than 50 mg; safety follow-up up to year 5 continues.
评估类风湿关节炎（RA）、银屑病关节炎（PsA）和强直性脊柱炎（AS）试验至第3年的戈利木单抗总体安全性。
对尽管接受了传统治疗但仍患有活动性RA（未使用过甲氨蝶呤、使用过甲氨蝶呤以及使用过抗TNF（肿瘤坏死因子）药物）、PsA或AS的患者，皮下注射（SC）每4周一次（q4wk）的50毫克和100毫克戈利木单抗进行评估。安慰剂对照持续至第24周（第52周，未使用过甲氨蝶呤的患者），在第16周（第28周，未使用过甲氨蝶呤的患者）可提前退出；随后，所有患者接受每4周一次的50毫克或100毫克戈利木单抗治疗。在盲法对照期结束后，戈利木单抗剂量可由研究者自行决定调整。本文报告的总体安全性分析包括来自安慰剂对照期和至第160周的非对照研究期的数据。罕见事件的发病率/100患者年（pt-yrs）的测定还包括来自一项IIb期试验的RA患者。
在5项戈利木单抗皮下注射的III期试验中，至第160周，639例患者接受了安慰剂，2226例患者接受了50毫克（n = 1249）和/或100毫克（n = 1501）戈利木单抗（由于允许无反应者提前退出，患者可能被纳入多个组）；1179例患者接受治疗≥156周。对于安慰剂、50毫克戈利木单抗和100毫克戈利木单抗，至第160周各自的不良事件发病率/100 pt-yrs（95%置信区间）为：死亡，分别为0.28（0.01至1.56）、0.30（0.12至0.62）、0.41（0.23至0.69）；严重感染，分别为5.31（3.20至8.30）、3.03（2.36至3.82）、5.09（4.36至5.90）；结核病，分别为0.00（0.00至0.84）、0.17（0.05至0.44）、0.35（0.18至0.62）；机会性感染，分别为0.00（0.00至0.84）、0.13（0.03至0.38）、0.24（0.10至0.46）；脱髓鞘，分别为0.00（0.00至0.84）、0.00（0.00至0.13）、0.12（0.03至0.30）；淋巴瘤，分别为0.00（0.00至0.84）、0.04（0.00至0.24）、0.18（0.06至0.38）。
至3年的戈利木单抗皮下注射安全性与其他TNF拮抗剂一致。100毫克戈利木单抗的严重感染、脱髓鞘事件和淋巴瘤的发病率在数值上高于50毫克；至第5年的安全性随访仍在继续。
