优特克单抗
优特克单抗是全人源化的抗IL-12和IL-23的抗体。 IL-23是一种细胞因子，通过结合Th17细胞表面上的IL-23受体促进Th17细胞分化和增殖。 IL-23受体基因的多态性增加了AS的发病风险。 优特克单抗对中到重度银屑病有治疗作用。[203]Papp KA, Langley RG, Lebwohl M, et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2). Lancet. 2008;371:1675-1684.http://www.ncbi.nlm.nih.gov/pubmed/18486740?tool=bestpractice.com[204]Leonardi CL, Kimball AB, Papp KA, et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1). Lancet. 2008;371:1665-1674.http://www.ncbi.nlm.nih.gov/pubmed/18486739?tool=bestpractice.com 根据 TOPAS 研究（一项前瞻性、开放性、单组、概念验证临床试验）的结果，在基线时、第 4 周和第 16 周时对 20 例活动性 AS 患者皮下注射乌司奴单抗 (ustekinumab) 90 mg 可减少活动性 AS 的体征和症状，且耐受性良好。[205]Poddubnyy D, Hermann KG, Callhoff J, et al. Ustekinumab for the treatment of patients with active ankylosing spondylitis: results of a 28-week, prospective, open-label, proof-of-concept study (TOPAS). Ann Rheum Dis. 2014;73:817-823.http://www.ncbi.nlm.nih.gov/pubmed/24389297?tool=bestpractice.com
利妥昔单抗
利妥昔单抗是针对B细胞的抗CD20的生物制剂。 一项包含20例慢性活动性AS患者的小型开放性试验显示，在24周的随访中，利妥昔单抗（基线期和2周后输注1000mg）能有效降低未接受过抗TNF治疗的患者的Bath强直性脊柱炎疾病活动度评分(BASDAI)、患者报告的脊柱疼痛程度、CRP水平。[206]Song IH, Heldmann F, Rudwaleit M, et al. Major clinical response of rituximab in active TNF-blocker-naive patients with ankylosing spondylitis but not in TNF-blocker-failure patients - an open label clinical trial [abstract]. ACR/ARHP Annual Scientific Meeting, Philadelphia, PA; 2009. Arthritis Rheum 2009;60(suppl 10):1769.http://www.blackwellpublishing.com/acrmeeting/abstract.asp?MeetingID=761&id=81393&meeting=ART 对抗TNF治疗反应差的患者对利妥昔单抗反应也差。[206]Song IH, Heldmann F, Rudwaleit M, et al. Major clinical response of rituximab in active TNF-blocker-naive patients with ankylosing spondylitis but not in TNF-blocker-failure patients - an open label clinical trial [abstract]. ACR/ARHP Annual Scientific Meeting, Philadelphia, PA; 2009. Arthritis Rheum 2009;60(suppl 10):1769.http://www.blackwellpublishing.com/acrmeeting/abstract.asp?MeetingID=761&id=81393&meeting=ART 更进一步的研究正在进行中。
阿普司特
阿普斯特 (Apremilast) 是一种口服磷酸二酯酶 4 抑制剂。一项 2 期概念验证试验结果显示，活动性 AS 患者经过 12 周治疗后，BASDAI 和 BASMI 评分出现绝对改善，但结果并没有达到统计学意义。[207]Pathan E, Abraham S, Van Rossen E, et al. Efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in ankylosing spondylitis. Ann Rheum Dis. 2013;72:1475-1480.http://www.ncbi.nlm.nih.gov/pubmed/22984171?tool=bestpractice.com 3 期临床试验正在进行中。[208]Celgene Corporation. Study of apremilast to treat subjects with active ankylosing spondylitis (POSTURE). NCT01583374. July 2014. clinicaltrials.gov/ (last accessed 29 November 2016).http://clinicaltrials.gov/ct2/show/NCT01583374
阿巴西普，妥珠单抗，sarilumab
早期的关于阿巴西普（T细胞共刺激分子）、妥珠单抗（静脉注射的全人源抗IL-6受体抗体）、sarilumab（皮下注射的全人源抗IL-6受体抗体）的II期早期试验显示这些药物对治疗AS无效。[209]Song IH, Heldmann F, Rudwaleit M, et al. Treatment of active ankylosing spondylitis with abatacept: an open-label, 24-week pilot study. Ann Rheum Dis. 2011;70:1108-1110.http://www.ncbi.nlm.nih.gov/pubmed/21415053?tool=bestpractice.com[210]Kiltz U, Heldmann F, Baraliakos X, et al. Treatment of ankylosing spondylitis in patients refractory to TNF-inhibition: are there alternatives? Curr Opin Rheumatol. 2012;24:252-260.http://www.ncbi.nlm.nih.gov/pubmed/22450391?tool=bestpractice.com[211]Sieper J, Braun J, Kay J, et al. Sarilumab for the treatment of ankylosing spondylitis: results of a Phase II, randomised, double-blind, placebo-controlled study (ALIGN). Ann Rheum Dis. 2015;74:1051-1057.http://ard.bmj.com/content/74/6/1051.longhttp://www.ncbi.nlm.nih.gov/pubmed/24550171?tool=bestpractice.com
针对其他病理过程的治疗
未来可能的治疗靶点包括JAK3（一种参与淋巴细胞活化和增殖的细胞信号转导分子，它可被口服的JAK3阻滞剂—托法替尼阻滞）、基质金属蛋白酶（可降解细胞外基质）、骨形态发生蛋白（参与骨质形成的TGF-β超家族成员）和Wnt信号通路（参与骨形成）。
