Herrick Ariane L, Pan Xiaoyan, Peytrignet Sébastien, Lunt Mark, Hesselstrand Roger, Mouthon Luc, Silman Alan, Brown Edith, Czirják László, Distler Jörg H W, Distler Oliver, Fligelstone Kim, Gregory William J, Ochiel Rachel, Vonk Madelon, Ancuţa Codrina, Ong Voon H, Farge Dominique, Hudson Marie, Matucci-Cerinic Marco, Balbir-Gurman Alexandra, Midtvedt Øyvind, Jordan Alison C, Jobanputra Paresh, Stevens Wendy, Moinzadeh Pia, Hall Frances C, Agard Christian, Anderson Marina E, Diot Elisabeth, Madhok Rajan, Akil Mohammed, Buch Maya H, Chung Lorinda, Damjanov Nemanja, Gunawardena Harsha, Lanyon Peter, Ahmad Yasmeen, Chakravarty Kuntal, Jacobsen Søren, MacGregor Alexander J, McHugh Neil, Müller-Ladner Ulf, Riemekasten Gabriela, Becker Michael, Roddy Janet, Carreira Patricia E, Fauchais Anne Laure, Hachulla Eric, Hamilton Jennifer, İnanç Murat, McLaren John S, van Laar Jacob M, Pathare Sanjay, Proudman Susannah, Rudin Anna, Sahhar Joanne, Coppere Brigitte, Serratrice Christine, Sheeran Tom, Veale Douglas J, Grange Claire, Trad Georges-Selim, Denton Christopher P
Centre for Musculoskeletal Research, The University of Manchester, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
Ann Rheum Dis. 2017 Jul;76(7):1207-1218. doi: 10.1136/annrheumdis-2016-210503. Epub 2017 Feb 10.
The rarity of early diffuse cutaneous systemic sclerosis (dcSSc) makes randomised controlled trials very difficult. We aimed to use an observational approach to compare effectiveness of currently used treatment approaches.
This was a prospective, observational cohort study of early dcSSc (within three years of onset of skin thickening). Clinicians selected one of four protocols for each patient: methotrexate, mycophenolate mofetil (MMF), cyclophosphamide or 'no immunosuppressant'. Patients were assessed three-monthly for up to 24 months. The primary outcome was the change in modified Rodnan skin score (mRSS). Confounding by indication at baseline was accounted for using inverse probability of treatment (IPT) weights. As a secondary outcome, an IPT-weighted Cox model was used to test for differences in survival.
Of 326 patients recruited from 50 centres, 65 were prescribed methotrexate, 118 MMF, 87 cyclophosphamide and 56 no immunosuppressant. 276 (84.7%) patients completed 12 and 234 (71.7%) 24 months follow-up (or reached last visit date). There were statistically significant reductions in mRSS at 12 months in all groups: -4.0 (-5.2 to -2.7) units for methotrexate, -4.1 (-5.3 to -2.9) for MMF, -3.3 (-4.9 to -1.7) for cyclophosphamide and -2.2 (-4.0 to -0.3) for no immunosuppressant (p value for between-group differences=0.346). There were no statistically significant differences in survival between protocols before (p=0.389) or after weighting (p=0.440), but survival was poorest in the no immunosuppressant group (84.0%) at 24 months.
These findings may support using immunosuppressants for early dcSSc but suggest that overall benefit is modest over 12 months and that better treatments are needed.
NCT02339441.
早期弥漫性皮肤系统性硬化症（dcSSc）病例罕见，使得随机对照试验极具难度。我们旨在采用观察性方法比较当前所用治疗方法的疗效。
这是一项针对早期dcSSc（皮肤增厚起病三年内）的前瞻性观察队列研究。临床医生为每位患者选择四种方案之一：甲氨蝶呤、霉酚酸酯（MMF）、环磷酰胺或“不使用免疫抑制剂”。对患者每三个月评估一次，为期最长24个月。主要结局指标是改良Rodnan皮肤评分（mRSS）的变化。采用治疗逆概率（IPT）权重来处理基线时的指征性混杂因素。作为次要结局指标，使用IPT加权Cox模型来检验生存率的差异。
从50个中心招募的326例患者中，65例使用甲氨蝶呤，118例使用MMF，87例使用环磷酰胺，56例不使用免疫抑制剂。276例（84.7%）患者完成了12个月随访，234例（71.7%）完成了24个月随访（或至末次就诊日期）。所有组在12个月时mRSS均有统计学意义的降低：甲氨蝶呤组为-4.0（-5.2至-2.7）单位，MMF组为-4.1（-5.3至-2.9）单位，环磷酰胺组为-3.3（-4.9至-1.7）单位，不使用免疫抑制剂组为-2.2（-4.0至-0.3）单位（组间差异p值 = 0.346）。各方案在加权前（p = 0.389）或加权后（p = 0.440）的生存率均无统计学意义的差异，但不使用免疫抑制剂组在24个月时生存率最低（84.0%）。
这些发现可能支持在早期dcSSc中使用免疫抑制剂，但提示在12个月期间总体获益不大，仍需要更好的治疗方法。
NCT02339441。
