Prednisone

得了类风湿关节炎（RA），您一定有很多困惑：药该怎么吃？关节疼时能不能运动？饮食上要注意什么？……别急，这份指南就是为您量身打造的“避坑宝典”。 我们特意根据权威的2020《类风湿关节炎患者实践指南》中，为您精挑细选了16条最接地气、最管用的核心建议——没有晦涩的医学术语，只有您日常最关心的问题和清清楚楚的答案。每一条都经过了专家严格把关，并用数字和字母标出了“靠谱程度”，让您一看就懂，心中有数。 证据等级小贴士（方便您判断这条建议有多“硬核”）： 数字（1级＞2级）：代表推荐强度，1级是“强力推荐”，2级是“中等推荐”。 字母（A＞B＞C＞D）：代表证据质量，A级最严谨，D级相对较弱（但依然有参考价值）。 放心，这只是给您做个参考，重点还是内容本身对您有用。希望这16条建议，能帮您少走弯路，更有信心地管理好自己的身体。收藏这一份，随时翻看，您的康复路上，我们始终相伴。💪 01、RA疾病基础认知（无证据等级） 类风湿关节炎（RA）是慢性、全身性自身免疫性疾病，核心损伤部位为关节滑膜、软骨及骨质，长期发病可引发关节破坏、关节畸形，严重时导致残疾。 该病并非只损伤关节，还会累及全身多个系统，包括皮肤、血管、眼部、呼吸系统、心血管系统、血液系统、神经系统、泌尿系统等。 流行病学数据显示，我国RA患病率为0.2%～0.4%。 02、单纯类风湿因子（RF）阳性不能确诊RA（1A 高等级推荐） 类风湿因子（RF）阳性≠类风湿关节炎，不可单一指标判定病情。 临床需结合抗CCP抗体、关节受累情况、炎症指标等多项结果综合评估。同时，RF数值会随病情轻重波动，可作为疗效评估的参考指标。 03、RA存在明确遗传倾向（2C） RA发病由遗传、环境、免疫三大因素共同主导。 遗传风险：RA患者一级亲属患病率为0.6%～1.8%；携带HLA-DRB1基因人群，患病风险提升5～10倍。 温馨提示：子代即便携带风险基因，也不一定会发病，无需过度焦虑。 04、抗CCP抗体检查可预测关节破坏严重程度（1B） 抗环瓜氨酸多肽（抗CCP）抗体是RA核心特异性指标，与关节破坏进展高度相关。 1. 该抗体可在发病数年之前提前检出，具备疾病预警价值； 2. 定期检测抗CCP抗体，可精准评估病情进展、治疗效果及疾病缓解状态。 05、针灸可作为RA辅助治疗手段（2D） 针灸可通过抗炎、抗氧化、调节机体免疫的机制，有效缓解RA患者关节疼痛，尤其适用于膝、踝、肩关节不适。 同时可辅助降低血沉（ESR）、C反应蛋白（CRP），减少关节肿胀数量，临床可联合中医科、针灸科协同治疗。 06、RA合并焦虑需及时干预治疗（2C） 临床数据显示：30%～60%的RA患者伴随焦虑症状，多由长期病痛、病情反复引发。 干预方案： ✅ 轻中度焦虑：加强疾病科普认知、调整心态、规律控病即可改善； ✅ 重度焦虑（影响日常生活）：风湿科联合心理专科诊疗，可规范使用三环类抗抑郁药物，同时坚持RA基础靶向药、传统DMARDs药物治疗。 07、RA合并睡眠障碍可多维度改善（2D） 约60% RA患者存在睡眠质量下降、失眠等问题（包括入睡困难、睡眠维持困难和早醒），与关节疼痛、炎症、心理压力密切相关。 改善方案： 1. 心理疗法和药物治疗：      规范RA抗炎治疗，从根源缓解疼痛、改善睡眠；      严重失眠：首选认知行为心理干预，必要时使用非苯二氮䓬类助眠药物； 2. 运动：坚持散步、游泳等温和运动，有效提升睡眠质量。 08、RA患者需科学运动，分阶段锻炼（2C） 运动是RA康复的关键，需根据病情分期选择运动方式，避免盲目锻炼加重损伤。 ✅ 急性期：以静养休息为主，配合简单关节活动度训练，防止关节僵硬粘连； ✅ 稳定期：适度增加有氧运动、力量训练、柔韧性训练（推荐散步、游泳）； ❌ 禁忌：避免高强度负重、高冲击剧烈运动。 09、RA患者必须严格戒烟（2C） 吸烟是RA发病、病情加重的独立危险因素，危害明确： 1. 提升患病风险：男性风险提升1.87倍，女性风险提升1.31倍； 2. 加速关节骨质破坏，加重病情进展； 3. 大幅降低生物制剂疗效（如英夫利昔单抗应答率下降77%）。 10、病情持续缓解可规范减量生物制剂（1B） 满足以下条件，可在医生指导下减量生物制剂： 1. 已停用糖皮质激素，或泼尼松用量＜7.5mg/d； 2. 病情持续缓解满6个月以上； 3. 持续服用传统DMARDs基础药物。 减量方式：可延长用药间隔、减少单次剂量，全程需定期复查监测，严防病情复发。 11、甲氨蝶呤备孕、孕期、哺乳期规范要求（1C 高等级推荐） 甲氨蝶呤存在明确胚胎毒性、致畸性，严格禁忌用于妊娠期、哺乳期女性。 备孕要求：需停药满3个月以上方可备孕，停药期间可补充叶酸，严格戒酒（合并使用的肝毒性）。 12、来氟米特备孕、孕期、哺乳期规范要求（1C 高等级推荐） 来氟米特具有致畸性，妊娠期、哺乳期严格禁用。 特殊注意：该药肝肠循环代谢极慢，停药后2年仍可能在血中检出药物残留。 备孕要求：需在医生指导下服用考来烯胺加速药物清除，血药浓度检测为0后，方可备孕。         RA处于活动期的孕妇，发生早产、低出生体重儿的概率亦较大。 13、常规补充钙+维生素D，预防骨质疏松（1C 高等级推荐） RA患者长期炎症刺激、激素用药，会大幅提升骨质疏松、骨折风险，需主动干预： 1. 定期通过FRAX工具评估骨折、骨质疏松风险；             FRAX 测量工具可浏览 http：//www.shef.ac.uk/FRAX         2. 积极控制关节炎症         3.常规补充钙剂、维生素D（激素用药患者必补）； 4. 高风险人群可使用双膦酸盐类药物，抑制骨吸收、降低骨折风险。 14、关节彩超可预测病情复发（2C） 处于疾病缓解期的RA患者，可通过关节彩色超声检查发现亚临床滑膜炎，提前预判复发风险。 高危复发因素：药物减量/停药、抗CCP抗体持续阳性、超声提示亚临床滑膜炎。存在任意1项及以上，需密切复诊监测。 15、重视用药期间肝损伤防控（2C） RA患者长期、联合用药易引发药物性肝损伤，需全程做好防控：         1.识别肝损害的危险因素：包括饮酒、老年人、女性、肥胖、合用其他肝毒性药物以及已存在肝脏疾病，上述因素中有部分可以控制。         2. 用药前：完善肝功能、病毒性肝炎筛查评估；  3. 用药期间：严格戒酒，定期复查肝功能；服用甲氨蝶呤者可补充叶酸。出现肝损伤指标异常，立即停药并及时就诊干预。 4. 停药后：持续监测肝损伤发生征象，停药后仍有慢性肝损伤的可能。         患者应注意是否出现肝损伤的征象，如心神不安、皮疹、低烧、胃口差、恶心、呕吐、右上腹疼痛、小便黄赤、皮肤瘙痒和皮肤发黄等。 16、长期参与病友会助力病情康复（1C 高等级推荐） RA患者定期、长期参与病友会可显著获益：通过系统的疾病健康教育，能够有效改善关节疼痛、肿胀症状，缓解负面情绪、降低抑郁评分。 规范的病友交流与健康指导，可长期稳定病情、优化疾病预后。 结语：以上16条指南推荐意见覆盖RA疾病认知、检查诊疗、用药安全、备孕生育、康复运动、心理护理、并发症预防等全维度内容，建议患者对照参考，遵医嘱规范治疗、科学养护。 10.3760/cma.j.cn112138-20200807-00734

Approval based on AZUR-1 data showing clinically significant proportion of participants with no detectable signs of cancer one year or more after treatment No disease recurrences reported among responders after median follow up of more than two years Jemperli monotherapy could help eligible patients avoid chemotherapy, radiation and surgery PHILADELPHIA--(BUSINESS WIRE)-- #AZUR --GSK plc (LSE/NYSE: GSK) today announced the US Food and Drug Administration (FDA) has approved Jemperli (dostarlimab-gxly) as the first and only immunotherapy for adults with stage II and III microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) locally advanced rectal cancer under the accelerated approval pathway. Current standard of treatment for locally advanced rectal cancer includes chemotherapy, radiation and surgery 1 , but these can have lasting consequences, including bowel, urinary and sexual dysfunction, secondary cancers and infertility 2,3 . For patients with MSI-H/dMMR tumors, a biomarker found in around 5-10% of rectal cancers 4 , Jemperli monotherapy could help avoid these interventions. Tony Wood, Chief Scientific Officer, GSK, said: “Today, Jemperli becomes the first and only approved immunotherapy for adults in the US with MSI-H/dMMR locally advanced rectal cancer. For decades, treatment has relied on chemotherapy, radiation and surgery. This approval offers a new treatment approach and represents an important step towards more personalized care for these patients.” Dr. Andrea Cercek, MD, Principal Investigator of AZUR-1, Section Head of Colorectal Cancer and Co-Director of the Center for Young Onset Colorectal and Gastrointestinal Cancer, Memorial Sloan Kettering Cancer Center, said: “The AZUR-1 results demonstrate the potential for a fundamentally different treatment approach in this biomarker-defined patient population, and today’s approval means MSI-H/dMMR patients can now access a licensed treatment tailored to the biology of their disease.” Michael Sapienza, CEO, Colorectal Cancer Alliance, said: “People facing rectal cancer are often thinking not only about treating their disease, but also worrying about what life will look like afterwards. The possibility of avoiding chemotherapy, radiation and surgery represents a meaningful advance for patients and their families. Biomarker testing at diagnosis will be essential to identifying patients who may be eligible for this treatment and helping them understand their options.” Approval was based on data from the phase II AZUR-1 trial. The study met its primary objective, demonstrating a clinically significant proportion of participants achieved sustained clinical complete responses at 12 months (cCR12), with data continuing to mature. Investigator-assessed data, a clinically relevant endpoint, showed 68% of evaluable patients (98/144; 95% CI: 60%, 76%) achieved cCR12. In an exploratory analysis, 76% (110/144; 95% CI: 69%, 83%) of evaluable patients had no evidence of cancer one year or more after treatment. This includes 68% (98/144) (95% CI: 60%, 76%) of patients who reached cCR12 without surgery, plus other participants (n=12) who had their complete response confirmed through tissue analysis after surgery (pathological complete response, or pCR). No disease recurrences have been reported among responders to date, after a median follow up of more than two years. Data on the primary objective, cCR12 assessed by Independent Central Review, continue to mature. 47% (54/116) (95% CI: 37%, 56%) of evaluable patients have achieved cCR12. An additional 38 participants who are still progressing through to 12 month follow up have already achieved a clinical complete response. The safety pro Jemperli was generally consistent with its established pro solid tumors. Serious adverse reactions occurred in 20% of patients receiving Jemperli, and the most common adverse reactions were fatigue (32%), rash (22%), diarrhea (18%) and pruritus (17%). Jemperli was permanently discontinued due to adverse reactions in 3% of patients. Full data from the AZUR-1 interim analysis will be presented at the European Society for Medical Oncology (ESMO) Congress in October 2026. Jemperli has received FDA Fast Track and Breakthrough Therapy designations for this indication. The application was also granted Priority Review and received a National Priority Voucher, resulting in an accelerated approval ahead of the PDUFA date. The supplemental Biologics License Application (sBLA) is being reviewed under Project Orbis, an FDA Oncology Center of Excellence initiative that enables concurrent review by international health authorities. Regulatory reviews are ongoing in participating countries. About stage II/III MSI-H/dMMR locally advanced rectal cancer Around 5–10% of rectal cancers are microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) 4 . These tumors have a specific genetic characteristic where they are unable to properly repair DNA damage, leading to an accumulation of mutations. This unique biological feature often makes them highly responsive to immunotherapies like dostarlimab-gxly 5,6 . These biomarkers are commonly found in colorectal, endometrial and other gastrointestinal cancers, but can also be present in other solid tumors 7 . About AZUR-1 AZUR-1 is a global, open-label, single-arm, registrational phase II trial evaluating dostarlimab-gxly monotherapy in patients (n=154) with previously untreated stage II and III MSI-H/dMMR locally advanced rectal cancer. The trial was designed to assess clinical complete responses sustained for 12 months (cCR12) as determined by Independent Central Review, and to determine whether dostarlimab-gxly alone could enable patients to avoid chemotherapy, radiation and surgery. Additional efficacy outcomes include cCR12 based on investigator assessment and objective response rate (ORR), defined as patients who achieved cCR, clinical near-complete response, or clinical partial response as their best overall response. Patients received nine cycles of dostarlimab-gxly over six months, administered as a 500mg intravenous infusion every three weeks. The safety and tolerability pro dostarlimab-gxly was generally consistent with its well-characterized safety pro across solid tumors. Serious adverse reactions occurred in 20% of patients receiving Jemperli and treatment was permanently discontinued due to adverse reactions in 3% of patients. The most common adverse reactions (≥15%) were fatigue, rash, diarrhea and pruritus. About Jemperli (dostarlimab-gxly) Jemperli , a programmed death receptor-1 (PD-1)-blocking antibody, plays an important role in GSK’s immune-oncology research and development program. A robust clinical trial program includes studies of Jemperli alone and in combination with other therapies in gynecologic, colorectal, and head and neck cancers, as well as where there are opportunities for transformational outcomes. Jemperli was discovered by AnaptysBio, Inc. and licensed to TESARO, Inc., under a collaboration and exclusive license agreement signed in March 2014. Under this agreement, GSK is responsible for the ongoing research, development, commercialization and manufacturing of Jemperli . More information about the product and its currently approved indications is available at EU product information 8 and US product information 9 . Indications and Important Safety Information for JEMPERLI (dostarlimab-gxly) JEMPERLI, in combination with carboplatin and paclitaxel, followed by JEMPERLI as a single agent, is indicated for the treatment of adult patients with primary advanced or recurrent endometrial cancer (EC). JEMPERLI, as a single agent, is indicated for the treatment of adult patients with mismatch repair deficient (dMMR) recurrent or advanced: EC, as determined by an FDA-authorized test, that has progressed on or following prior treatment with a platinum-containing regimen in any setting and are not candidates for curative surgery or radiation, or solid tumors, as determined by an FDA-authorized test, that have progressed on or following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). JEMPERLI, as a single agent, is indicated for the treatment of adult patients with Stage II/III, locally advanced rectal cancer (LARC) that is microsatellite instability-high (MSI-H) or dMMR, as determined by an FDA-authorized test for solid tumors. This indication is approved under accelerated approval based on sustained clinical complete response for 12 months. The long-term risk of relapse is unknown, with additional follow-up expected. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). Important Safety Information Severe and Fatal Immune-Mediated Adverse Reactions Immune-mediated adverse reactions, which can be severe or fatal, can occur in any organ system or tissue and can occur at any time during or after treatment with a PD-1/PD-L1–blocking antibody, including JEMPERLI. Monitor closely for signs and symptoms of immune-mediated adverse reactions. Evaluate liver enzymes, creatinine, and thyroid function tests at baseline and periodically during treatment. For suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate. Based on the severity of the adverse reaction, withhold or permanently discontinue JEMPERLI. In general, if JEMPERLI requires interruption or discontinuation, administer systemic corticosteroids (1 to 2 mg/kg/day prednisone or equivalent) until improvement to ≤Grade 1. Upon improvement to ≤Grade 1, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reaction is not controlled with corticosteroids. Immune-Mediated Pneumonitis JEMPERLI can cause immune-mediated pneumonitis, which can be fatal. In patients treated with other PD-1/PD-L1–blocking antibodies, the incidence of pneumonitis is higher in patients who have received prior thoracic radiation. Pneumonitis occurred in 2% (15/759) of patients receiving JEMPERLI as a single agent, including Grade 2 (1.2%), Grade 3 (0.7%), and Grade 4 (0.1%) pneumonitis. Immune-Mediated Colitis Colitis occurred in 1.2% (9/759) of patients receiving JEMPERLI as a single agent, including Grade 2 (0.7%) and Grade 3 (0.5%) adverse reactions. Cytomegalovirus infection/reactivation have occurred in patients with corticosteroid-refractory immune-mediated colitis. In such cases, consider repeating infectious workup to exclude alternative etiologies. Immune-Mediated Hepatitis JEMPERLI can cause immune-mediated hepatitis, which can be fatal. Grade 3 hepatitis occurred in 0.5% (4/759) of patients receiving JEMPERLI as a single agent. Immune-Mediated Endocrinopathies Adrenal Insufficiency Adrenal insufficiency occurred in 1.1% (8/759) of patients receiving JEMPERLI as a single agent, including Grade 2 (0.4%) and Grade 3 (0.7%). For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment per institutional guidelines, including hormone replacement as clinically indicated. Withhold or permanently discontinue JEMPERLI depending on severity. Hypophysitis JEMPERLI can cause immune-mediated hypophysitis. Grade 3 hypophysitis occurred in 0.4% (1/241) of patients receiving JEMPERLI in combination with carboplatin and paclitaxel. Grade 2 hypophysitis occurred in 0.3% (2/759) of patients receiving JEMPERLI as a single agent. Initiate hormone replacement as clinically indicated. Withhold or permanently discontinue JEMPERLI depending on severity. Thyroid Disorders Grade 2 thyroiditis occurred in 0.4% (3/759) of patients receiving JEMPERLI as a single agent. Grade 2 hypothyroidism occurred in 12% (30/241) of patients receiving JEMPERLI in combination with carboplatin and paclitaxel. Grade 2 hypothyroidism occurred in 8% (58/759) of patients receiving JEMPERLI as a single agent. Hyperthyroidism occurred in 3.3% (8/241) of patients receiving JEMPERLI in combination with carboplatin and paclitaxel, including Grade 2 (2.9%) and Grade 3 (0.4%). Hyperthyroidism occurred in 2.2% (17/759) of patients receiving JEMPERLI as a single agent, including Grade 2 (2.1%) and Grade 3 (0.1%). Initiate thyroid hormone replacement or medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue JEMPERLI depending on severity. Type 1 Diabetes Mellitus, Which Can Present with Diabetic Ketoacidosis JEMPERLI can cause type 1 diabetes mellitus, which can present with diabetic ketoacidosis. Grade 3 type 1 diabetes mellitus occurred in 0.4% (1/241) of patients receiving JEMPERLI in combination with carboplatin and paclitaxel. Grade 3 type 1 diabetes mellitus occurred in 0.1% (1/759) of patients receiving JEMPERLI as a single agent. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold or permanently discontinue JEMPERLI depending on severity. Immune-Mediated Nephritis with Renal Dysfunction JEMPERLI can cause immune-mediated nephritis, which can be fatal. Grade 2 nephritis, including tubulointerstitial nephritis, occurred in 0.4% (3/759) of patients receiving JEMPERLI as a single agent. Immune-Mediated Dermatologic Adverse Reactions JEMPERLI can cause immune-mediated rash or dermatitis. Bullous and exfoliative dermatitis, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS), have occurred with PD-1/PD-L1–blocking antibodies. One patient receiving JEMPERLI experienced Grade 3 SJS, which resolved. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-bullous/exfoliative rashes. Withhold or permanently discontinue JEMPERLI depending on severity. Other Immune-Mediated Adverse Reactions The following clinically significant immune-mediated adverse reactions occurred in 2%) were decreased lymphocytes, decreased sodium, increased alanine aminotransferase, increased creatinine, decreased neutrophils, decreased albumin, and increased alkaline phosphatase. The most common adverse reactions (≥20%) in patients with dMMR solid tumors who received JEMPERLI as a single agent were fatigue/asthenia, anemia, diarrhea, and nausea. The most common Grade 3 or 4 laboratory abnormalities (≥2%) were decreased lymphocytes, decreased sodium, increased alkaline phosphatase, and decreased albumin. The most common adverse reactions (≥15%) in patients with MSI-H/dMMR LARC who received JEMPERLI as a single agent were fatigue, rash, diarrhea, and pruritus. The most common Grade 3 or 4 laboratory abnormalities (≥2%) were decreased lymphocytes, decreased hemoglobin, and increased AST. Please see full Prescribing Information, including Medication Guide. GSK in oncology Our ambition in oncology is to help increase overall quality of life, maximize survival and change the course of disease, expanding from our current focus on blood and women’s cancers into lung and gastrointestinal cancers, as well as other solid tumors. This includes accelerating priority programs such as antibody-drug conjugates Ris-Rez targeting B7-H3 and Mo-Rez targeting B7-H4, and velzatinib, a highly selective KIT tyrosine kinase inhibitor. About GSK GSK is a global biopharma company with a purpose to unite science, technology, and talent to get ahead of disease together. Find out more at Cautionary statement regarding forward-looking statements GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described in the “Risk Factors” section in GSK’s Annual Report on Form 20-F for 2025, and GSK’s Q2 Results for 2026. Registered in England & Wales: No. 3888792 Registered Office: 79 New Oxford Street London WC1A 1DG References: Cercek A, Lumish M, Sinopoli J, et al. PD-1 blockade in mismatch repair–deficient, locally advanced rectal cancer. N Engl J Med 2022; 386: 2363-76. Negro, S. et al. (2025) ‘Quality of life in rectal cancer treatments: a systematic review’, Cancers, 17(14), 2310. Available at: Neibart, S.S. et al. (2020) ‘Quality of life after radiotherapy for rectal cancer’, Current Colorectal Cancer Reports, 16(1), pp. 1–10. Available at: Cercek A, et al. Mismatch Repair-Deficient Rectal Cancer and Resistance to Neoadjuvant Chemotherapy. Clin Cancer Res. 2020 Jul 1;26(13):3271-3279. doi: 1158/1078-0432.CCR-19-3728. Epub 2020 Mar 6. PMID: 32144135; PMCID: PMC7348681. Andre T, Berton D, Curigliano G, et al. Antitumor Activity and Safety of Dostarlimab Monotherapy in Patients With Mismatch Repair Deficient Solid Tumors: A Nonrandomized Controlled Trial. JAMA Netw Open. 2023;6(11):e2341165. doi:10.1001/jamanetworkopen.2023.41165. Le DT, et al. PD-1 blockade in tumors with mismatch repair deficiency. N Engl J Med. 2015;372(26):2509-2520. National Cancer Institute at the National Institutes of Health. Definition of mismatch repair deficiency. Accessed September 2026. Available at: JEMPERLI (dostarlimab) Summary of Product Characteristics. GlaxoSmithKline (Ireland) Limited. Available at: Accessed October 2026. JEMPERLI (dostarlimab-gxly) prescribing information. GlaxoSmithKline. Available at: Accessed October 2026. Memorial Sloan Kettering Cancer Center Disclosure: Dr Cercek has financial interests related to GSK. Contacts GSK inquiries Media: Tim Foley +44 (0) 20 8047 5502 (London) Sarah Clements +44 (0) 20 8047 5502 (London) Kathleen Quinn +1 202 603 5003 (Washington DC) Alison Hunt +1 540 742 3391 (Washington DC) Stephanie Caccomo +1 202 893 2840 (Washington DC) Investor Relations: James Dodwell +44 (0) 7881 269066 (London) Mick Readey +44 (0) 7990 339653 (London) Joanna Tuplin +44 (0) 7788 351650 (London) Sam Piper +44 (0) 7824 525779 (London) Dan Smith +44 (0) 7823 523885 (London) Jeff McLaughlin +1 215 751 7002 (Philadelphia) Frannie DeFranco +1 215 751 3126 (Philadelphia)