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Abstract：
BACKGROUND: Established thresholds for patient-reported outcomes (PROs) provide clinically relevant responder data from trials. Lorecivivint (LOR) is an intra-articular (IA) therapy in development for knee osteoarthritis (OA). A post hoc analysis from a phase 2b trial (NCT03122860) determined proportions of LOR responders.
METHODS: A 24-week, randomized trial of 0.07 mg LOR demonstrated PRO improvements compared with PBO in moderate-to-severe knee OA participants. Participants treated with LOR and PBO achieving 30%/50%/70% improvements at weeks 12 and 24 in Pain Numeric Rating Scale (NRS), WOMAC Pain/Function subscales, Patient Global Assessment (PtGA), and OMERACT-OARSI responder criteria were determined. Odds ratios (ORs) and 95% confidence intervals [CIs] were compared with PBO.
RESULTS: There were 115 and 116 participants in the LOR and PBO groups, respectively. For Pain NRS, LOR increased ORs of achieving 30% [week 12, OR = 2.47 (1.45, 4.19), P < 0.001; week 24, OR = 2.37 (1.40, 4.02), P < 0.01] and 50% [week 24, OR = 1.89 (1.11, 3.23), P < 0.05] improvements over baseline. For WOMAC Pain, LOR increased ORs of achieving 30% [week 24, OR = 1.79 (1.06, 3.01), P < 0.05] and 50% [week 12, OR = 1.79 (1.06, 3.03), P < 0.05; week 24, OR = 1.73 (1.02, 2.93), P < 0.05] improvements. For WOMAC Function, LOR increased ORs of achieving 30% [week 12, OR = 1.85 (1.10, 3.12), P < 0.05; week 24, OR = 1.93 (1.14, 3.26), P < 0.05] improvements. For PtGA, LOR increased ORs of achieving 50% [week 12, OR = 2.28 (1.25, 4.16), P < 0.01] improvements. LOR produced numerical increases at the 70% threshold. LOR increased ORs of achieving OMERACT-OARSI responses [week 12, OR = 2.21 (1.29, 3.78); P < 0.01; week 24, OR = 2.57 (1.49, 4.43), P < 0.001] and strict responses [week 12, OR = 2.13 (1.26, 3.61), P < 0.01; week 24, OR = 2.05 (1.21, 3.47), P < 0.01].
CONCLUSIONS: LOR (0.07 mg) demonstrated improved PRO threshold responses across single and composite measures of pain, function, and patient global assessment compared with PBO, with benefits sustained to 24 weeks.
Lorecivivint (LOR) is a new injectable medicine being studied as a treatment for knee osteoarthritis (OA). An early (phase 2b) trial found participants with moderate-to-severe knee OA receiving LOR on average reported improved pain, function, and reduced impact of OA symptoms over 24 weeks compared with placebo. To consider how likely individuals were to respond to treatment, this study analyzed how many participants per group achieved different percentage levels of symptom improvement. Participants were given a single LOR or placebo injection into their most painful (target) knee at trial initiation. Participants reported their target knee status from day 1 (baseline) to week 24 using pain and function questionnaires. We analyzed the number of participants given 0.07 mg LOR and placebo whose symptom scores improved by 30, 50, and 70% over baseline scores at weeks 12 and 24. Results showed that 0.07 mg LOR treatment produced a higher likelihood beyond chance at week 12 of achieving a 30% improvement in some pain and function scores and a 50% improvement in other symptom scores compared with placebo. Similar 30% and 50% symptom score improvements were found at week 24. More complex scores, combining individual symptom scores into single index measures, also showed improvements beyond chance for 0.07 mg LOR from baseline compared with placebo at weeks 12 and 24. Thus, more participants with knee OA who were treated with 0.07 mg LOR demonstrated long-lasting, meaningful improvements in pain and function compared to those given placebo.
METHODS: A 24-week, randomized trial of 0.07 mg LOR demonstrated PRO improvements compared with PBO in moderate-to-severe knee OA participants. Participants treated with LOR and PBO achieving 30%/50%/70% improvements at weeks 12 and 24 in Pain Numeric Rating Scale (NRS), WOMAC Pain/Function subscales, Patient Global Assessment (PtGA), and OMERACT-OARSI responder criteria were determined. Odds ratios (ORs) and 95% confidence intervals [CIs] were compared with PBO.
RESULTS: There were 115 and 116 participants in the LOR and PBO groups, respectively. For Pain NRS, LOR increased ORs of achieving 30% [week 12, OR = 2.47 (1.45, 4.19), P < 0.001; week 24, OR = 2.37 (1.40, 4.02), P < 0.01] and 50% [week 24, OR = 1.89 (1.11, 3.23), P < 0.05] improvements over baseline. For WOMAC Pain, LOR increased ORs of achieving 30% [week 24, OR = 1.79 (1.06, 3.01), P < 0.05] and 50% [week 12, OR = 1.79 (1.06, 3.03), P < 0.05; week 24, OR = 1.73 (1.02, 2.93), P < 0.05] improvements. For WOMAC Function, LOR increased ORs of achieving 30% [week 12, OR = 1.85 (1.10, 3.12), P < 0.05; week 24, OR = 1.93 (1.14, 3.26), P < 0.05] improvements. For PtGA, LOR increased ORs of achieving 50% [week 12, OR = 2.28 (1.25, 4.16), P < 0.01] improvements. LOR produced numerical increases at the 70% threshold. LOR increased ORs of achieving OMERACT-OARSI responses [week 12, OR = 2.21 (1.29, 3.78); P < 0.01; week 24, OR = 2.57 (1.49, 4.43), P < 0.001] and strict responses [week 12, OR = 2.13 (1.26, 3.61), P < 0.01; week 24, OR = 2.05 (1.21, 3.47), P < 0.01].
CONCLUSIONS: LOR (0.07 mg) demonstrated improved PRO threshold responses across single and composite measures of pain, function, and patient global assessment compared with PBO, with benefits sustained to 24 weeks.
Lorecivivint (LOR) is a new injectable medicine being studied as a treatment for knee osteoarthritis (OA). An early (phase 2b) trial found participants with moderate-to-severe knee OA receiving LOR on average reported improved pain, function, and reduced impact of OA symptoms over 24 weeks compared with placebo. To consider how likely individuals were to respond to treatment, this study analyzed how many participants per group achieved different percentage levels of symptom improvement. Participants were given a single LOR or placebo injection into their most painful (target) knee at trial initiation. Participants reported their target knee status from day 1 (baseline) to week 24 using pain and function questionnaires. We analyzed the number of participants given 0.07 mg LOR and placebo whose symptom scores improved by 30, 50, and 70% over baseline scores at weeks 12 and 24. Results showed that 0.07 mg LOR treatment produced a higher likelihood beyond chance at week 12 of achieving a 30% improvement in some pain and function scores and a 50% improvement in other symptom scores compared with placebo. Similar 30% and 50% symptom score improvements were found at week 24. More complex scores, combining individual symptom scores into single index measures, also showed improvements beyond chance for 0.07 mg LOR from baseline compared with placebo at weeks 12 and 24. Thus, more participants with knee OA who were treated with 0.07 mg LOR demonstrated long-lasting, meaningful improvements in pain and function compared to those given placebo.
摘要：
背景：为患者报告的结果（PRO）建立的阈值提供了来自试验的临床相关应答者数据。Lorecivivint（LOR）是一种开发用于膝骨关节炎（OA）的关节内（IA）疗法。来自2b期试验(NCT03122860)的事后分析确定了LOR应答者的比例。
方法：24周，0.07mgLOR的随机试验显示,在中重度膝关节OA参与者中,与PBO相比,PRO改善.接受LOR和PBO治疗的参与者在第12周和第24周疼痛数字评定量表（NRS）中达到30％/50％/70％的改善，WOMAC疼痛/功能分量表，患者全球评估（PtGA），并确定了OMERACT-OARSI应答者标准。将赔率比(ORs)和95%置信区间[CIs]与PBO进行比较。
结果：LOR和PBO组中有115和116名参与者，分别。对于疼痛NRS，LOR增加OR达到30%[第12周，OR=2.47（1.45，4.19），P<0.001；第24周，OR=2.37（1.40，4.02），P<0.01]和50%[第24周,OR=1.89(1.11,3.23),P<0.05]相对于基线的改善。对于WOMAC疼痛，LOR增加OR达到30%[第24周，OR=1.79（1.06，3.01），P<0.05和50%[第12周,OR=1.79(1.06,3.03),P<0.05;第24周,OR=1.73(1.02,2.93),P<0.05]改善。对于WOMAC功能，LOR增加OR达到30%[第12周，OR=1.85（1.10，3.12），P<0.05;第24周,OR=1.93(1.14,3.26),P<0.05]改善。对于PtGA，LOR增加OR达到50%[第12周，OR=2.28(1.25，4.16)，P<0.01]改善。LOR在70%阈值处产生数值增加。LOR增加实现OMERACT-OARSI反应的OR[第12周,OR=2.21(1.29,3.78);P<0.01;第24周,OR=2.57(1.49,4.43),P<0.001和严格的反应[第12周，OR=2.13（1.26，3.61），P<0.01；第24周，OR=2.05（1.21，3.47），P<0.01]。
结论：LOR（0.07mg）在单一和复合疼痛测量中显示出改善的PRO阈值反应，函数,以及与PBO相比的患者全球评估，受益持续至24周。
Lorecivivint（LOR）是一种新的可注射药物，正在研究用于治疗膝骨关节炎（OA）。一项早期（2b期）试验发现，平均而言，接受LOR的中度至重度膝关节OA参与者的疼痛有所改善。函数,与安慰剂相比，24周内OA症状的影响降低。考虑个体对治疗有多大反应的可能性，这项研究分析了每组有多少参与者达到不同的症状改善百分比水平.在试验开始时，参与者被给予单次LOR或安慰剂注射到他们最疼痛的（目标）膝盖中。参与者使用疼痛和功能问卷报告了他们从第1天（基线）到第24周的目标膝关节状态。我们分析了在第12周和第24周，给予0.07mgLOR和安慰剂的参与者的数量，这些参与者的症状评分比基线评分提高了30％，50％和70％。结果显示，与安慰剂相比，0.07mgLOR治疗在第12周的某些疼痛和功能评分改善30％，其他症状评分改善50％的可能性更高。在第24周发现类似的30%和50%症状评分改善。更复杂的分数，将个体症状评分组合成单一指标，在第12周和第24周时,与安慰剂相比,0.07mgLOR与基线相比也显示出超出偶然性的改善.因此，更多接受0.07mgLOR治疗的膝关节OA参与者表现出持久的，与给予安慰剂相比，疼痛和功能有意义的改善。
方法：24周，0.07mgLOR的随机试验显示,在中重度膝关节OA参与者中,与PBO相比,PRO改善.接受LOR和PBO治疗的参与者在第12周和第24周疼痛数字评定量表（NRS）中达到30％/50％/70％的改善，WOMAC疼痛/功能分量表，患者全球评估（PtGA），并确定了OMERACT-OARSI应答者标准。将赔率比(ORs)和95%置信区间[CIs]与PBO进行比较。
结果：LOR和PBO组中有115和116名参与者，分别。对于疼痛NRS，LOR增加OR达到30%[第12周，OR=2.47（1.45，4.19），P<0.001；第24周，OR=2.37（1.40，4.02），P<0.01]和50%[第24周,OR=1.89(1.11,3.23),P<0.05]相对于基线的改善。对于WOMAC疼痛，LOR增加OR达到30%[第24周，OR=1.79（1.06，3.01），P<0.05和50%[第12周,OR=1.79(1.06,3.03),P<0.05;第24周,OR=1.73(1.02,2.93),P<0.05]改善。对于WOMAC功能，LOR增加OR达到30%[第12周，OR=1.85（1.10，3.12），P<0.05;第24周,OR=1.93(1.14,3.26),P<0.05]改善。对于PtGA，LOR增加OR达到50%[第12周，OR=2.28(1.25，4.16)，P<0.01]改善。LOR在70%阈值处产生数值增加。LOR增加实现OMERACT-OARSI反应的OR[第12周,OR=2.21(1.29,3.78);P<0.01;第24周,OR=2.57(1.49,4.43),P<0.001和严格的反应[第12周，OR=2.13（1.26，3.61），P<0.01；第24周，OR=2.05（1.21，3.47），P<0.01]。
结论：LOR（0.07mg）在单一和复合疼痛测量中显示出改善的PRO阈值反应，函数,以及与PBO相比的患者全球评估，受益持续至24周。
Lorecivivint（LOR）是一种新的可注射药物，正在研究用于治疗膝骨关节炎（OA）。一项早期（2b期）试验发现，平均而言，接受LOR的中度至重度膝关节OA参与者的疼痛有所改善。函数,与安慰剂相比，24周内OA症状的影响降低。考虑个体对治疗有多大反应的可能性，这项研究分析了每组有多少参与者达到不同的症状改善百分比水平.在试验开始时，参与者被给予单次LOR或安慰剂注射到他们最疼痛的（目标）膝盖中。参与者使用疼痛和功能问卷报告了他们从第1天（基线）到第24周的目标膝关节状态。我们分析了在第12周和第24周，给予0.07mgLOR和安慰剂的参与者的数量，这些参与者的症状评分比基线评分提高了30％，50％和70％。结果显示，与安慰剂相比，0.07mgLOR治疗在第12周的某些疼痛和功能评分改善30％，其他症状评分改善50％的可能性更高。在第24周发现类似的30%和50%症状评分改善。更复杂的分数，将个体症状评分组合成单一指标，在第12周和第24周时,与安慰剂相比,0.07mgLOR与基线相比也显示出超出偶然性的改善.因此，更多接受0.07mgLOR治疗的膝关节OA参与者表现出持久的，与给予安慰剂相比，疼痛和功能有意义的改善。
