Abstract：
OBJECTIVE: Fibrodysplasia ossificans progressiva (FOP) is one of the most catastrophic forms of genetic heterotopic ossification (HO). FOP is characterized by severe, progressive inflammatory flare-ups, that often lead to HO. The flare-ups are associated with increased inflammatory cytokine production, suggesting auto-inflammatory features driven by interleukin-1β (IL-1β). This study describes the short- and long-term responses of FOP patients to anti-IL-1 therapy.
METHODS: Previously, we reported that a patient with FOP treated with anti-IL-1 agents showed dramatically lower rates of flare-ups, improved flare-up symptoms, decreased use of glucocorticoids, and apparently decreased size of residual lesions. Plasma analyses also showed marked elevation in IL-1β levels during a FOP flare, further supporting a role of IL-1β in the pathogenesis of FOP flares. Here, we report results from long-term therapy with IL-1 inhibitors in that patient, and describe 3 additional patients, from two medical centers.
RESULTS: All 4 patients showed persistent improvement in flare activity during treatment with IL-1 inhibitors, with minimal formation of new HO sites. Two patients who stopped therapy experienced resurgence of flare activity that was re-suppressed upon re-initiation. These patients had IL-1β levels comparable to those in IL-1β-driven diseases. Child Health Assessment Questionnaires confirmed extensive subjective improvements in the pain and general health visual analogue scales.
CONCLUSIONS: This case series demonstrates significant benefits from IL-1 inhibitors for reducing flare activity and improving the general health of patients with FOP. These data provide strong support for additional studies to better understand the function of IL-1 inhibition, primarily in reducing formation new HO.
BACKGROUND: RH received support from the International FOP Association ACT grant; ECH received support from NIH/NIAMS R01AR073015 and the UCSF Robert Kroc Chair in Connective Tissue and Rheumatic Diseases III.
METHODS: Previously, we reported that a patient with FOP treated with anti-IL-1 agents showed dramatically lower rates of flare-ups, improved flare-up symptoms, decreased use of glucocorticoids, and apparently decreased size of residual lesions. Plasma analyses also showed marked elevation in IL-1β levels during a FOP flare, further supporting a role of IL-1β in the pathogenesis of FOP flares. Here, we report results from long-term therapy with IL-1 inhibitors in that patient, and describe 3 additional patients, from two medical centers.
RESULTS: All 4 patients showed persistent improvement in flare activity during treatment with IL-1 inhibitors, with minimal formation of new HO sites. Two patients who stopped therapy experienced resurgence of flare activity that was re-suppressed upon re-initiation. These patients had IL-1β levels comparable to those in IL-1β-driven diseases. Child Health Assessment Questionnaires confirmed extensive subjective improvements in the pain and general health visual analogue scales.
CONCLUSIONS: This case series demonstrates significant benefits from IL-1 inhibitors for reducing flare activity and improving the general health of patients with FOP. These data provide strong support for additional studies to better understand the function of IL-1 inhibition, primarily in reducing formation new HO.
BACKGROUND: RH received support from the International FOP Association ACT grant; ECH received support from NIH/NIAMS R01AR073015 and the UCSF Robert Kroc Chair in Connective Tissue and Rheumatic Diseases III.
摘要：
目的：进行性骨化性纤维发育不良（FOP）是遗传异位骨化（HO）的最灾难性形式之一。FOP的特点是严重，进行性炎症发作,这往往导致HO。发作与炎性细胞因子产生增加有关，提示由白细胞介素-1β（IL-1β）驱动的自身炎症特征。这项研究描述了FOP患者对抗IL-1治疗的短期和长期反应。
方法：以前，我们报道，用抗IL-1药物治疗的FOP患者表现出明显较低的发作率，改善发作症状，减少糖皮质激素的使用，残余病变的大小明显减小。血浆分析还显示，在FOP发作期间，IL-1β水平显著升高，进一步支持IL-1β在FOP耀斑发病机制中的作用。这里,我们报告了该患者长期使用IL-1抑制剂治疗的结果，并描述了另外3名患者，两个医疗中心。
结果：在使用IL-1抑制剂治疗期间，所有4例患者的耀斑活性持续改善，很少形成新的HO站点。两名停止治疗的患者经历了耀斑活动的复苏，该活动在重新开始时被重新抑制。这些患者的IL-1β水平与IL-1β驱动的疾病相当。儿童健康评估问卷证实了疼痛和一般健康视觉模拟量表的主观改善。
结论：本病例系列显示IL-1抑制剂对降低耀斑活性和改善FOP患者的一般健康状况具有显著益处。这些数据为其他研究提供了强有力的支持，以更好地理解IL-1抑制的功能，主要是在减少地层新HO。
背景：RH获得了国际FOP协会ACT拨款的支持；ECH获得了NIH/NIAMSR01AR073015和UCSFRobertKroc主席在结缔组织和风湿性疾病III的支持。
方法：以前，我们报道，用抗IL-1药物治疗的FOP患者表现出明显较低的发作率，改善发作症状，减少糖皮质激素的使用，残余病变的大小明显减小。血浆分析还显示，在FOP发作期间，IL-1β水平显著升高，进一步支持IL-1β在FOP耀斑发病机制中的作用。这里,我们报告了该患者长期使用IL-1抑制剂治疗的结果，并描述了另外3名患者，两个医疗中心。
结果：在使用IL-1抑制剂治疗期间，所有4例患者的耀斑活性持续改善，很少形成新的HO站点。两名停止治疗的患者经历了耀斑活动的复苏，该活动在重新开始时被重新抑制。这些患者的IL-1β水平与IL-1β驱动的疾病相当。儿童健康评估问卷证实了疼痛和一般健康视觉模拟量表的主观改善。
结论：本病例系列显示IL-1抑制剂对降低耀斑活性和改善FOP患者的一般健康状况具有显著益处。这些数据为其他研究提供了强有力的支持，以更好地理解IL-1抑制的功能，主要是在减少地层新HO。
背景：RH获得了国际FOP协会ACT拨款的支持；ECH获得了NIH/NIAMSR01AR073015和UCSFRobertKroc主席在结缔组织和风湿性疾病III的支持。
