Web-based Pain Coping Skills Training to Improve Pain and Poor Adherence caused by Aromatase Inhibitor-Associated Arthralgia In Breast Cancer Survivors (SKIP-Arthralgia): A Randomized Controlled Trial

芳香化酶抑制剂（AI）是绝经后乳腺癌幸存者（BCS）的标准治疗后护理 HR阳性（HR+）肿瘤AI可以提高生存率并降低癌症复发的风险，但 它们还造成严重的不利影响。最常见的是关节痛-关节疼痛和僵硬，影响 大约50%的BCS在启动AI后不久开始。疼痛的关节引起情绪困扰和穷人 健康相关生活质量（HRQoL）。这也是与AI依从性问题最密切相关的AI副作用， 这是一个严重的医疗问题。治疗疼痛性关节痛的当前医学和行为干预 仅对少数BCS有帮助，导致限制其使用的毒性，或证据不足，揭示了关键差距 限制了使用AI减少疼痛性关节痛对BCS影响的能力。我们建议填补这一关键空白， 疼痛应对技能训练（PCST），一种认知行为疗法（CBT）知情干预。对我们 尽管没有研究评估PCST用于治疗AI相关疼痛性关节痛， 随机对照试验（RCT）表明，PCST和类似的干预措施，由训练有素的治疗师提供 可以改善疼痛，减少癌症患者的残疾，慢性肌肉骨骼疼痛和其他疼痛 条件尽管有疗效，但由于高风险等障碍，PCST在临床护理中仍未得到充分利用。 资源成本，在某些地理区域缺乏可用性，患者的旅行要求，以及 训练有素的治疗师。我们开发了一个基于网络的PCST程序，称为painTRAINER，以克服这些障碍， 使用一种新的方法来优化参与并保留治疗师提供的治疗关键特征， PCST在一个“自动化”的程序，不需要治疗师的参与。PainTRAINER高度模仿 交互式和个性化的治疗师提供的PCST。RCT证据显示，painTRAINER 它可以接受和参与，并且可以减轻骨关节炎（OA）患者的关节疼痛和僵硬。我们 现在寻求评估它是否可以改善疼痛性关节痛的严重程度及其相关干扰， AI治疗对BCS的其他不良影响。拟定的多中心RCT将随机分配452例患有AI的BCS- 相关的疼痛性关节痛，以加强常规护理（EUC）或painTRAINER+EUC。评估将在 基线、干预后（基线后12周）以及干预后3个月和6个月。目的是 确定与EUC相比，painTRAINER+EUC是否改善了疼痛严重程度和疼痛干扰（目的 1，主要结局）以及痛苦、HRQoL和AI依从性（目标2，次要结局）。我们还将 确定这些对主要和次要结局的影响是否至少部分是由增加 疼痛自我效能和减少疼痛灾难化（目标3）。最后，为了探索性的目的，我们将评估 除了聚集参与者外，还对睡眠问题和血管紧张症状产生有益的间接影响 painTRAINER的反馈适合他们的独特需求。这项随机对照试验可以产生一种高度可传播的干预措施， 这可以在临床上迅速实施，包括在有限获得PCST的地理区域。

Aromatase inhibitors (AIs) are standard post-treatment care for postmenopausal breast cancer survivors (BCS) with hormone-receptor positive (HR+) tumors. AIs improve survival and reduce risk for cancer recurrence, but they also cause significant adverse effects. The most common is arthralgia—joint pain and stiffness that affects about 50% of BCS beginning soon after starting an AI. Painful arthralgia causes emotional distress and poor health-related quality of life (HRQoL). It is also the AI side effect most strongly linked to AI adherence problems, which are a critical medical concern. Current medical and behavioral interventions for managing painful arthralgia help only a minority of BCS, cause toxicities that limit their use, or have weak evidence, revealing a critical gap limiting ability to reduce the impact of painful arthralgia on BCS using AIs. We propose to fill this critical gap with Pain Coping Skills Training (PCST), a cognitive-behavioral therapy (CBT)-informed intervention. To our knowledge, no study has evaluated PCST for management of AI-associated painful arthralgia, although randomized controlled trials (RCTs) show that PCST and similar interventions delivered by trained therapists can improve pain and reduce disability in people with cancer, chronic musculoskeletal pain, and other pain conditions. Despite efficacy, PCST continues to be underused in clinical care due to barriers such as high resource costs, lack of availability in some geographic areas, travel requirements for patients, and a shortage of trained therapists. We developed a web-based PCST program called painTRAINER to overcome these barriers, using a novel approach to optimize engagement and retain therapeutically critical features of therapist-delivered PCST in an “automated” program that does not require therapist involvement. PainTRAINER mimics highly interactive and personalized therapist-delivered PCST. RCT evidence shows that painTRAINER is highly acceptable and engaging, and that it can reduce joint pain and stiffness in people with osteoarthritis (OA). We now seek to evaluate whether it can improve the severity of painful arthralgia and its associated interference and other adverse impacts on BCS on AI therapy. The proposed multi-site RCT will randomize 452 BCS with AI- associated painful arthralgia to enhanced usual care (EUC) or painTRAINER+EUC. Assessments will occur at baseline, post-intervention (12 weeks after baseline), and 3- and 6-months post-intervention. Aims are to determine whether painTRAINER+EUC, compared to EUC, improves pain severity and pain interference (Aim 1, primary outcomes) as well as distress, HRQoL, and AI adherence (Aim 2, secondary outcomes). We will also determine whether these effects on primary and secondary outcomes are at least partially mediated by increases in pain self-efficacy and reductions in pain catastrophizing (Aim 3). Finally, for an exploratory aim we will evaluate beneficial indirect effects on sleep problems and vasomotor symptoms in addition to gathering participant feedback on painTRAINER’s fit for their unique needs. This RCT could yield a highly disseminable intervention that could be quickly implemented clinically, including in geographic areas with limited access to PCST.