Факторы, влияющие на результаты анальгетической терапии. Результаты российского многоцентрового исследования НОТА (НПВП для Обезболивания: Терапевтический Анализ)
Факторы, влияющие на результаты анальгетической терапии. Результаты российского многоцентрового исследования НОТА (НПВП для Обезболивания: Терапевтический Анализ)
Факторы, влияющие на результаты анальгетической терапии. Результаты российского многоцентрового исследования НОТА (НПВП для Обезболивания: Терапевтический Анализ)
Нестероидные противовоспалительные препараты (НПВП) – основные средства контроля боли при распространенных скелетно-мышечных заболеваниях, таких как остеоартрит (ОА) и неспецифическая боль в спине (НБС). Однако до настоящего времени не изучены факторы, влияющие на эффективность этих препаратов. Цель исследования. Определить факторы, влияющие на эффективность НПВП. Материалы и методы. Проведено наблюдательное исследование, в котором оценивалась эффективность 2-недельного курса НПВП при ОА и НБС в реальной клинической практике. Исследуемую группу составили 3604 больных с ОА и НБС (60,6% женщин и 39,4% мужчин, средний возраст – 55,0±13,4 года). Согласно плану исследования, оценивались результаты применения ацеклофенака (Аэртал®) и любых других НПВП, назначенных лечащими врачами (соотношение назначений 1:1). Основным критерием эффективности была частота полного купирования боли через 2 нед после начала терапии. Дополнительно определялась динамика боли и самочувствия по 10-балльной числовой рейтинговой шкале (ЧРШ). Для выявления факторов, влияющих на эффективность НПВП, проведено сопоставление частоты купирования боли у пациентов, имевших и не имевших изучаемые факторы, с определением показателя отношения шансов (ОШ). Результаты и обсуждение. Большинство больных получали ацеклофенак (54,9%), а также диклофенак (2,0%), кетопрофен (1,9%), лорноксикам (2,2%), мелоксикам (13,7%), напроксен (2,1%), нимесулид (5,8%), целекоксиб (5,9%), эторикоксиб (7,1%) и другие НПВП (4,4%); 56,2% больных получали миорелаксанты, в основном толперизон (74,7%), витамины группы В (10,4%), а также ингибиторы протонного насоса (42,8%).
Купирование боли достигнуто у 54,8% пациентов. Снижение уровня боли и улучшение общего самочувствия составило (по ЧРШ) 63,9±13,4% и 61,7±14,8% соответственно. Эффективность ацеклофенака оказалась выше, чем в целом в группе: при его использовании боль купирована у 59,9% больных. Нежелательные явления при использовании ацеклофенака отмечены у 2,3% больных, других НПВП – от 2,4 до 14,1%.
Вероятность купирования боли оказалась выше у мужчин: ОШ 1,239 (95% доверительный интервал – ДИ – 1,08–1,418; р=0,002), у имевших первый эпизод боли – ОШ 3,341 (95% ДИ 2,873–3,875; р=0,000), хороший «ответ» на НПВП в анамнезе – ОШ 1,656 (95% ДИ 1,385–1,980; р=0,000) и получавших НПВП в комбинации с миорелаксантами – ОШ 1,218 (95% ДИ 1,067–1,390; р=0,004). Эффект терапии ниже у больных 65 лет и старше – ОШ 0,378 (95% ДИ 0,324–0,442; р=0,000), с индексом массы тела >30 кг/м2 – ОШ 0,619 (95% ДИ 0,529–0,723; р=0,000), с выраженной болью (≥7 баллов ЧРШ) – ОШ 0,662 (95% ДИ 0,580–0,756; р=0,002), с болью, возникающей в покое, – ОШ 0,515 (95% ДИ 0,450–0,589; р=0,000), ночью – ОШ 0,581 (95% ДИ 0,501–0,672; р=0,000) и наличием чувства скованности – ОШ 0,501 (95% ДИ 0,438–0,573; р=0,000). Результаты лечения достоверно хуже при сочетании боли в спине и суставах, а также боли в области trochanter major и «гусиной лапки» (р<0,001). Заключение. НПВП являются средством выбора для лечения боли при НБС и ОА. Ацеклофенак эффективен и безопасен при данной патологии. При проведении анальгетической терапии следует учитывать факторы, влияющие на эффективность лечения: пожилой возраст, избыточную массу тела, недостаточный эффект НПВП в анамнезе, выраженную боль, признаки «воспалительной» боли, множественные источники болевых ощущений.
Non-steroidal anti-inflammatory drugs (NSAIDs) are most popular medications for the treatment of pain in common musculoskeletal diseases such as osteoarthritis (OA) and non-specific low back pain (LBP). However, the factors affecting the effectiveness of these drugs have not been determined fully. Aim: to identify factors affecting the effectiveness of NSAIDs in patients with OA and LBP. Materials and methods. An observational study was conducted to evaluate the effectiveness of a 2-week course of NSAIDs in OA and LBP in real clinical practice. The study group consisted of 3604 patients with OA and LBP (60.6% women and 39.4% men, mean age 55.0±13.4 years). According to the study design, aceclofenac (Airtal) and other NSAIDs used in the ratio 1:1. The main criterion of effectiveness was the frequency of complete pain relief after 2 weeks of therapy. In addition, the decrease of pain and general health were determined on a 10-point numerical rating scale (NRS). We compared the frequency of complete pain relief in patients who had and did not have the studied factors. The value of the studied factors was determined using OR (95% CI). Results and discussion. Most patients received aceclofenac (54.9%), as well as diclofenac (2.0%), ketoprofen (1.9%), lornoxicam (2.2%), meloxicam (13.7%), naproxen (2.1%), nimesulide (5.8%), celecoxib (5.9%), ethicoxib (7.1%) and other NSAIDs (4.4%); 56.2% of patients received muscle relaxants, mainly tolperisone (74.7%), vitamin B (10.4%), and proton pump inhibitors (42.8%).
Complete pain relief was achieved in 54.8% of patients. The pain decrease and general health improvement were (for NRS) 63.9±13.4% and 61.7±14.8%, respectively. The efficacy of aceclofenac was slightly higher than in the whole group: complete pain relief was in 59.9% of patients. Adverse events in aceclofenac use were observed in 2.3% of patients, other NSAIDs-from 2.4 to 14.1%.
The frequency of complete pain relief was higher in men: OR 1,239 (95% CI 1.08–1.418; p=0.002), who had the first episode of pain – OR 3.341 (95% CI 2.873–3.875; p=0.000), a good" response " to NSAIDs in history – OR 1.656 (95% CI 1.385–1.980; p=0.000) and received NSAIDs in combination with muscle relaxants – OR 1.218 (95% CI 1.067-1.390; p=0.004). The effect of therapy is lower in patients 65 years and older-OR 0,378 (95% CI 0.324–0.442; p=0,000), with body mass index >30 kg/m² – OR 0.619 (95% CI 0.529–0.723; p=0.000), with severe pain (≥7 points NRS) – OR 0.662 (95% CI 0.580–0.756; p=0.002), with pain at rest, – OR 0.515 (95% CI 0.450–0,589; p=0.000), pain at night – OR 0.581 (95% CI 0.501–0.672; p=0.000) and the presence of stiffness – OR 0.501 (95% CI 0.438–0,573; p=0.000). Treatment results are significantly worse in the cases of combination of LBP and joint pain, as well as pain in the trochanter major and pes anserinus area (p<0.001). Conclusion. NSAIDs are the first-line medications for the pain treatment in LBP and OA. Aceclofenac is effective and safe in this conditions. When carrying out analgesic therapy should take into account factors that affect the effectiveness of treatment: old age, overweight, insufficient effect of NSAIDs in history, severe pain, signs of "inflammatory" pain, multiple sources of pain.
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2. Scarpignato C, Lanas A, Blandizzi C, et al. Safe prescribing of non-steroidal anti-inflammatory drugs in patients with osteoarthritis – an expert consensus addressing benefits as well as gastrointestinal and cardiovascular risks. BMC Medicine. 2015;13:55. doi: 10.1186/s 12916-015-0285-8
3. Sarganas G, Buttery AK, Zhuang W, et al. Prevalence, trends, patterns and associations of analgesic use in Germany. BMC Pharmacol Toxicol. 2015 Oct 1;16:28. doi: 10.1186/s40360-015-0028-7
4. Van de Laar M, Pergolizzi J, Mellinghoff H, et al. Pain Treatment in Arthritis-Related Pain: Beyond NSAIDs. Open Rheumatol J. 2012;6: 320-30.
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6. Koes BW, van Tulder M, Lin CW, Macedo LG, McAuley J, Maher C. An updated overview of clinical guidelines for the management of non-specific low back pain in primary care. Eur Spine J. 2010 Dec;19(12):2075-94.
7. Qaseem A, Wilt TJ, McLean RM, et al. Noninvasive Treatments for Acute, Subacute, and Chronic Low Back Pain: A Clinical Practice Guideline From the American College of Physicians. Ann Intern Med. 2017 Feb 14. doi: 10.7326/M16-2367 [Epub ahead of print].
8. Pelletier JP, Martel-Pelletier J, Rannou F, Cooper C. Efficacy and safety of oral NSAIDs and analgesics in the management of osteoarthritis: Evidence from real-life setting trials and surveys. Semin Arthritis Rheum. 2016 Feb;45(4 Suppl):S22-7. doi: 10.1016/j.semarthrit.2015. 11.009. Epub 2015 Dec 2.
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11. Доступно по ссылке: https://www.iqvia.com/our-customers/pharmaceutical-manufacturers
12. Da Costa BR, Reichenbach S, Keller N, et al. Effectiveness of non-steroidal anti-inflammatory drugs for the treatment of pain in knee and hip osteoarthritis: a network meta-analysis. Lancet. 2017 Jul 8;390(10090):e21-e33. doi: 10.1016/S0140-6736(17)31744-0
13. Stam W, Jansen J, Taylor S. Efficacy of etoricoxib, celecoxib, lumiracoxib, non-selective NSAIDs, and acetaminophen in osteoarthritis: a mixed treatment comparison. Open Rheumatol J. 2012;6:6-20.
doi: 10.2174/1874312901206010006. Epub 2012 Apr 3.
14. Moore RA, Smugar SS, Wang H, et al. Numbers-needed-to-treat analyses – do timing, dropouts, and outcome matter? Pooled analysis of two randomized, placebo-controlled chronic low back pain trials. Pain. 2010 Dec;151(3):592-7. doi: 10.1016/j.pain.2010.07.013
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16. Dooley M, Spencer C, Dunn C. Aceclofenac: a reappraisal of its use in the management of pain and rheumatic disease. Drugs. 2001;61(9): 1351-78.
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19. Schiltenwolf M, Pogatzki-Zahn EM. Pain medicine from intercultural and gender-related perspectives. Schmerz. 2015 Oct;29(5):569-75.
doi: 10.1007/s00482-015-0038-9
20. Fillingim RB, King CD, Ribeiro-Dasilva MC, et al. Sex, gender, and pain: a review of recent clinical and experimental findings. J Pain. 2009 May;10(5):447-85. doi: 10.1016/j.jpain.2008.12.001
21. Machado GC, Maher CG, Ferreira PH, et al. Can Recurrence After an Acute Episode of Low Back Pain Be Predicted? Phys Ther. 2017 Sep 1;97(9):889-95. doi: 10.1093/ptj/pzx067
22. Da Silva T, Mills K, Brown BT, et al. Risk of Recurrence of Low Back Pain: A Systematic Review. J Orthop Sports Phys Ther. 2017 May;47(5):305-13. doi: 10.2519/jospt.2017.7415. Epub 2017.
23. Beal BR, Wallace MS. An Overview of Pharmacologic Management of Chronic Pain. Med Clin North Am. 2016 Jan;100(1):65-79.
doi: 10.1016/j.mcna.2015.08.006. Epub 2015 Oct 27.
24. Roelofs PD, Deyo RA, Koes BW, Scholten RJ, van Tulder MW. Non-steroidal anti-inflammatory drugs for low back pain. Cochrane Database Syst Rev. 2008 Jan 23;(1):CD000396. doi: 10.1002/14651858. CD000396.pub3
25. Enthoven WT, Roelofs PD, Deyo RA, et al. Non-steroidal anti-inflammatory drugs for chronic low back pain. Cochrane Database Syst Rev. 2016 Feb 10;2:CD012087.
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________________________________________________
1. [Nasonov EL, Yakhno NN, Karateev AE, et al. General principles of treatment for musculoskeletal pain: Interdisciplinary consensus. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2016;54(3):247-65 (In Russ.)]. doi: 10.14412/1995-4484-2016-247-265
2. Scarpignato C, Lanas A, Blandizzi C, et al. Safe prescribing of non-steroidal anti-inflammatory drugs in patients with osteoarthritis – an expert consensus addressing benefits as well as gastrointestinal and cardiovascular risks. BMC Medicine. 2015;13:55. doi: 10.1186/s 12916-015-0285-8
3. Sarganas G, Buttery AK, Zhuang W, et al. Prevalence, trends, patterns and associations of analgesic use in Germany. BMC Pharmacol Toxicol. 2015 Oct 1;16:28. doi: 10.1186/s40360-015-0028-7
4. Van de Laar M, Pergolizzi J, Mellinghoff H, et al. Pain Treatment in Arthritis-Related Pain: Beyond NSAIDs. Open Rheumatol J. 2012;6: 320-30.
5. Crofford LJ. Use of NSAIDs in treating patients with arthritis. Arthritis Res Ther. 2013;15 Suppl 3:S2. doi: 10.1186/ar4174. Epub 2013 Jul 24.
6. Koes BW, van Tulder M, Lin CW, Macedo LG, McAuley J, Maher C. An updated overview of clinical guidelines for the management of non-specific low back pain in primary care. Eur Spine J. 2010 Dec;19(12):2075-94.
7. Qaseem A, Wilt TJ, McLean RM, et al. Noninvasive Treatments for Acute, Subacute, and Chronic Low Back Pain: A Clinical Practice Guideline From the American College of Physicians. Ann Intern Med. 2017 Feb 14. doi: 10.7326/M16-2367 [Epub ahead of print].
8. Pelletier JP, Martel-Pelletier J, Rannou F, Cooper C. Efficacy and safety of oral NSAIDs and analgesics in the management of osteoarthritis: Evidence from real-life setting trials and surveys. Semin Arthritis Rheum. 2016 Feb;45(4 Suppl):S22-7. doi: 10.1016/j.semarthrit.2015. 11.009. Epub 2015 Dec 2.
9. Bruyère O, Cooper C, Pelletier JP, et al. A consensus statement on the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) algorithm for the management of knee osteoarthritis-From evidence-based medicine to the real-life setting. Semin Arthritis Rheum. 2016 Feb;45(4 Suppl):S3-11.
doi: 10.1016/j.semarthrit.2015.11.010. Epub 2015 Dec 2.
10. [Zdravookhranenie v Rossii. 2017: Statisticheskiy sbornik [Public health in Russia. 2017: Statistical Digest]. Moscow: Rosstat; 2017. 170 p. (In Russ.)]. ISBN 978-5-89476-448-1 http://www.gks.ru
11. Доступно по ссылке: https://www.iqvia.com/our-customers/pharmaceutical-manufacturers
12. Da Costa BR, Reichenbach S, Keller N, et al. Effectiveness of non-steroidal anti-inflammatory drugs for the treatment of pain in knee and hip osteoarthritis: a network meta-analysis. Lancet. 2017 Jul 8;390(10090):e21-e33. doi: 10.1016/S0140-6736(17)31744-0
13. Stam W, Jansen J, Taylor S. Efficacy of etoricoxib, celecoxib, lumiracoxib, non-selective NSAIDs, and acetaminophen in osteoarthritis: a mixed treatment comparison. Open Rheumatol J. 2012;6:6-20.
doi: 10.2174/1874312901206010006. Epub 2012 Apr 3.
14. Moore RA, Smugar SS, Wang H, et al. Numbers-needed-to-treat analyses – do timing, dropouts, and outcome matter? Pooled analysis of two randomized, placebo-controlled chronic low back pain trials. Pain. 2010 Dec;151(3):592-7. doi: 10.1016/j.pain.2010.07.013
15. [Igolkina EV, Chichasova NV, Imametdinova GR. Aceclofenac in the treatment of diseases of the locomotor apparatus. Sovremennaya Revmatologiya = Modern Rheumatology Journal. 2017;11(3):99-105 (In Russ.)]. doi: 10/14412/1996-7012-2017-3-99-105
16. Dooley M, Spencer C, Dunn C. Aceclofenac: a reappraisal of its use in the management of pain and rheumatic disease. Drugs. 2001;61(9): 1351-78.
17. Patel PB, Patel TK. Efficacy and safety of aceclofenac in osteoarthritis: A meta-analysis of randomized controlled trials. Eur J Rheumatol. 2017 Mar;4(1):11-8. doi: 10.5152/eurjrheum.2017.160080. Epub 2017 Mar 1.
18. [Karateev AE, Tsurgan AV. Aceclofenac: the experience of Russian studies. Sovremennaya Revmatologiya = Modern Rheumatology Journal. 2017;11(4):89-94 (In Russ.)]. doi: 10/14412/1996-7012-2017-4-89-94
19. Schiltenwolf M, Pogatzki-Zahn EM. Pain medicine from intercultural and gender-related perspectives. Schmerz. 2015 Oct;29(5):569-75.
doi: 10.1007/s00482-015-0038-9
20. Fillingim RB, King CD, Ribeiro-Dasilva MC, et al. Sex, gender, and pain: a review of recent clinical and experimental findings. J Pain. 2009 May;10(5):447-85. doi: 10.1016/j.jpain.2008.12.001
21. Machado GC, Maher CG, Ferreira PH, et al. Can Recurrence After an Acute Episode of Low Back Pain Be Predicted? Phys Ther. 2017 Sep 1;97(9):889-95. doi: 10.1093/ptj/pzx067
22. Da Silva T, Mills K, Brown BT, et al. Risk of Recurrence of Low Back Pain: A Systematic Review. J Orthop Sports Phys Ther. 2017 May;47(5):305-13. doi: 10.2519/jospt.2017.7415. Epub 2017.
23. Beal BR, Wallace MS. An Overview of Pharmacologic Management of Chronic Pain. Med Clin North Am. 2016 Jan;100(1):65-79.
doi: 10.1016/j.mcna.2015.08.006. Epub 2015 Oct 27.
24. Roelofs PD, Deyo RA, Koes BW, Scholten RJ, van Tulder MW. Non-steroidal anti-inflammatory drugs for low back pain. Cochrane Database Syst Rev. 2008 Jan 23;(1):CD000396. doi: 10.1002/14651858. CD000396.pub3
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1 V.A. Nasonova Research Institute of Rheumatology, Moscow, Russia;
2 Autonomous Healthcare Institution "Irkutsk Clinical Hospital №1", Irkutsk, Russia;
3 Volgograd State Medical University, Volgograd, Russia;
4 Orel Regional Clinical Hospital, Orel, Russia;
5 S.V.Ochapovskiy Regional Clinical Hospital №1, Ministry of Health of Krasnodar Region, Krasnodar, Russia;
6 Clinic of medical expertise, LLC, Vladimir, Russia;
7 Novosibirsk State Medical University, Novosibirsk, Russia;
8 Voronezh Regional Clinical Hospital №1, Voronezh, Russia;
9 Budgetary State Institution "Regional Hospital" Tver, Russia;
10 Murmansk Regional Clinical Hospital named after P.A. Bayandin, Murmansk, Russia;
11 Kursk State Medical University, Kursk, Russia;
12 Rostov Regional Clinical Hospital №2, Rostov-on-Don, Russia
13 Chelyabinsk Regional Clinical Hospital, Chelyabinsk, Russia;
14 North-Western State Medical University named after I.I. Mechnikov, Saint-Petersburg, Russia;
15 Belgorod Regional Clinical Hospital, Belgorod, Russia;
16 Irkutsk State Medical Academy for Postgraduate Education, Irkutsk, Russia;
17 Arkhangelsk Regional Clinical Hospital, Arkhangelsk, Russia;
18 Professor S.I. Sergeev Regional Clinical Hospital №1, Khabarovsk, Russia;
19 Tula Regional Clinical Hospital, Tula, Russia;
20 The State Budget Health Care Institution of Stavropol Territory «Stavropol Regional Clinical Center of Specialized Types of Medical Care» Stavropol, Russia;
21 Kazan State Medical University, Kazan, Russia