Оценка 12-недельной уратснижающей терапии аллопуринолом в сочетании с нестероидным противовоспалительным препаратом мелоксикам у больных с подагрой
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Gromova M.A., Tsurko V.V., Kislyak O.A., Malysheva N.V. Evaluation of a 12-week allopurinol-lowering therapy in combination with the non-steroidal anti-inflammatory drug meloxicam in patients with gout. Therapeutic Archive. 2020; 92 (6): 60–68.
DOI: 10.26442/00403660.2020.06.000704
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Материалы и методы. Аллопуринол назначался внутрь, 1 раз в день. Каждые 3 нед дозировка препарата увеличивалась на 50 мг до 300 мг в день под контролем уровня сывороточной мочевой кислоты. Суммарная суточная доза препарата Мовалис, применяемого в виде разных лекарственных форм, составляла 7,5–15 мг. Клиническую эффективность лечения оценивали через 3, 6, 9 и 12 нед по данным физикального осмотра, динамике суставной боли в покое, при движении и пальпации, по визуальной аналоговой шкале в миллиметрах, шкале Лайкерта, опроснику EuroQol-5D-5L, уходу за собой, привычной повседневной деятельности, наличию тревоги и депрессии, оценке удовлетворенности лечением (по шкале от 1 до 5, где 1 – полное отсутствие улучшения или ухудшение, а 5 – очень хороший результат); учитывали период ремиссии, а также время до появления рецидива подагрического артрита. Проводилась регистрация неблагоприятных явлений.
Результаты и обсуждение. На фоне лечения Мовалисом 7,5 мг в день больше чем у 2/3 пациентов не отмечалось ухудшения суставного синдрома при увеличении дозы аллопуринола до 300 мг в день. К 12-й неделе наблюдения выявлено достоверное различие между выраженностью характеристик подагрического артрита в сторону улучшения показателей подвижности, ухода за собой, привычной повседневной деятельности, снижения болезненности, уменьшения тревоги и депрессии (p<0,05). Кроме того, достоверно различались уровни СОЭ и сывороточной мочевой кислоты исходно и в конечной точке наблюдения (p<0,05), что свидетельствует о положительном влиянии на воспалительный процесс. Трехмесячный курс комбинированной терапии не сопровождался значительными подъемами артериального давления, изменениями клиренса креатинина в сыворотке крови. Отсутствовали нежелательные явления со стороны желудочно-кишечного тракта. Результат лечения как очень хороший оценили 90,9% пациентов. Неблагоприятное явление в виде кожной аллергической сыпи отмечалось у одного больного, оно не потребовало прерывания лечения и полностью купировалось без последствий после завершения курса.
Заключение. Двенадцатинедельная сочетанная терапия уратснижающим препаратом аллопуринолом на фоне противовоспалительного приема препарата Мовалис предотвращает обострение суставного синдрома и улучшает качество жизни больных подагрой.
Ключевые слова: подагра, гиперурикемия, мочевая кислота, аллопуринол, мелоксикам, лечение, эффективность, безопасность.
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Aim. To evaluate a 12-week course of combined alloturinol-lowering therapy with a prophylactic anti-inflammatory dose of movalis for the frequency of exacerbations and the quality of life of patients with gout.
Materials and methods. Allopurinol was administered orally, 1 time per day. Every 3 weeks, the dosage of the drug was increased by 50 mg to 300 mg per day under the control of the level of serum uric acid (sUA). The total daily dose of the drug movalis, used in the form of different dosage forms, was 7.5–15 mg. The clinical effectiveness of the treatment was evaluated after 3, 6, 9 and 12 weeks according to physical examination, the dynamics of joint pain at rest, during movement and palpation, according to the visual analogue scale (VAS) in millimeters, Likert scale, EuroQol-5D-5L questionnaire, care for oneself, habitual daily activities, the presence of anxiety and depression, assessment of satisfaction with treatment (on a scale of 1 to 5, where 1 is the complete absence of improvement or worsening, and 5 is a very good result); took into account the period of remission, as well as the time before the onset of relapse of gouty arthritis. An adverse event (AE) was recorded.
Results and discussion. On the background of treatment with movalis 7.5 mg per day more than two-thirds of patients showed no worsening of the articular syndrome with an increase in the dose of allopurinol to 300 mg per day. By the 12th week of observation, a significant difference was found between the severity of gouty arthritis characteristics in the direction of improving mobility, self-care, normal daily activities, reducing soreness, reducing anxiety and depression (p<0.05). In addition, the ESR and sUA levels were significantly different initially and at the final observation point (p<0.05), which indicates a positive effect on the inflammatory process. A 3-month course of combination therapy was not accompanied by significant increases in blood pressure, changes in creatinine clearance in blood serum. There were no adverse events from the gastrointestinal tract. 90.9% of patients rated the treatment result as very good. AE in the form of a skin allergic rash was observed in one patient; it did not require interruption of treatment and completely stopped without consequences after completion of the course.
Conclusion. 12 – a week-long combined therapy of the allopurinol-reducing drug with the anti-inflammatory dose movalis prevents the exacerbation of the articular syndrome and improves the quality of life of patients with gout.
Keywords: gout, hyperuricemia, uric acid, allopurinol, meloxicam, treatment, effectiveness, safety.
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annrheumdis-2019-215315
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6. Choi HK, Atkinson K, Karlson EW, Curhan G. Purine-rich foods, dairy and protein intake, and the risk of gout in men. New Engl J Med. 2004;350(11):1093-103. doi: 10.1056/nejmoa035700
7. Zhang Y, Woods R, Chaisson CE, et al. Alcohol consumption as a trigger of recurrent gout attacks. Am J Med. 2006;119(9):800.e11-800.e16. doi: 10.1016/j.amjmed.2006.01.020
8. Choi HK, Atkinson K, Karlson EW, Curhan G. Obesity, weight change, hypertension, diuretic use, and risk of gout in men: the health professionals follow-up study. Arch Intern Med. 2005;165(7):742-8. doi: 10.1001/archinte.165.7.742
9. Hootman JM, Helmick CG. Projections of US prevalence of arthritis and associated activity limitations. Arthrit Rheumatol. 2006;54:226-9. doi: 10.1002/art.21562
10. Newberry SJ, FitzGerald JD, Motala A, et al. Diagnosis of Gout: A Systematic Review in Support of an American College of Physicians Clinical Practice Guideline. Arch Intern Med. 2017;166(1):27-36. doi: 10.7326/M16-0462
11. Rees F, Jenkins W, Doherty M. Patients with gout adhere to curative treatment if informed appropriately: proof-of-concept observational study. Ann Rheum Dis. 2013;72:826-30. doi: 10.1136/annrheumdis-2012-201676
12. De Vera MA, Marcotte G, Rai S, et al. Medication adherence in gout: asystematic review. Arth Care Res. 2014;66(10):1551-9. doi: 10.1002/acr.22336
13. Yin R, Li L, Zhang G, et al. Rate of adherence to urate-loweringtherapy among patients with gout: a systematic review and meta-analysis. BMJ Open. 2018;8(4):e017542. doi: 10.1136/bmjopen-2017-017542
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17. Wortmann RL, Macdonald PA, Hunt B, Jackson RL. Effect of prophylaxis on gout flares after the initiation of urate-lowering therapy: analysis of data from three phase III trials. Clin Ther. 2010;32:2386-97. doi: 10.1016/j.clinthera.2011.01.008
18. Kydd AS, Seth R, Buchbinder R, et al. Uricosuric medications for chronic gout. Cochrane Database System Rev. 2014;(11):CD01045. doi: 10.1002/14651858.cd010457.pub2
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22. Keenan RT, O’Brien WR, Lee KH, et al. Prevalence of contra indications and prescription of pharmacologic therapies for gout. Am J Med. 2011;124:155-63. doi: 10.1016/j.amjmed.2010.09.012
23. Asghar W, Jamali F. The effect of COX-2-selective meloxicam on the myocardial, vascular and renal risks: a systematic review. Inflammopharmacol. 2015;23(1):1-16. doi: 10.1007/s10787-014-0225-9
24. Yang M, Wang HT, Zhao M, et al. Network Meta-Analysis Comparing Relatively Selective COX-2 Inhibitors Versus Coxibs for the Prevention of NSAID-Induced Gastrointestinal Injury. Medicine. 2015;94(40):e1592. doi: 10.1097/md.0000000000001592
25. Arfè A, Scotti L, Varas-Lorenzo C, et al. Non-steroidal anti-inflammatory drugs and risk of heart failure in four European countries: nested case-control study. BMJ. 2016:i4857. doi: 10.1136/bmj.i4857
26. Varas-Lorenzo C, Riera-Guardia N, Calingaert B, et al. Myocardial infarction and individual nonsteroidal anti-inflammatory drugs meta-analysisof observational studies. Pharmacoepidemiol Drug Safety. 2013;22(6):559-70. doi: 10.1002/pds.3437
27. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J. 2018 Sep 1;39(33):3021-104. doi: 10.1093/eurheartj/
ehy339, published 25.08.2018
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29. Roglic G, Norris SL. Medicines for treatment intensification in type 2 diabetes and type of insulin in type 1 and type 2 diabetes in low-resource settings: Synopsis of the World Health Organization guidelines on second- and third-line medicines and type of insulin for the control of blood glucose levels in nonpregnant adults with diabetes mellitus. Ann Intern Med. 2018;169(6):394. doi: 10.7326/M18-1149
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31. National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification and Stratification. Am J Kidney Dis. 2002;39(Suppl. 1):1-266. https://www.ncbi.nlm.nih.gov/pubmed/11904577
32. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. 2013. https://kdigo.org/wp-content/uploads/2017/02/KDIGO_2012_CKD_GL.pdf
33. Wittens C, Davies AH, Bækgaard N, et al. Editor's Choice – Management of Chronic Venous Disease: Clinical Practice Guidelines of the European Society for Vascular Surgery (ESVS). Eur J Vasc Endovasc Surg. 2015;49(6):678-737. doi: 10.1016/j.ejvs.2015.02.007
34. Hawker GA, Mian S, Kendzerska T, French M. Measures of adult pain: Visual Analog Scale for Pain (VAS Pain), Numeric Rating Scale for Pain (NRS Pain), McGill Pain Questionnaire (MPQ), Short-Form McGill Pain Questionnaire (SF-MPQ), Chronic Pain Grade Scale (CPGS), Short Form-36 Bodily Pain Scale (SF-36 BPS), and Measure of Intermittent and Constant Osteoarthritis Pain (ICOAP). Arth Care Res. 2011;63(Suppl. 11):S240-S252. doi: 10.1002/acr.20543
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________________________________________________
1. Richette P, Bardin T. Gout. Lancet. 2010;375(9711):318-28. doi: 10.1016/S0140-6736(09)60883-7
2. Rossiyskiye klinicheskiye rekomendatsii. Revmatologiya. Pod red. E.L. Nasonovа. Moscow: GEOTAR-Media, 2017; p. 253-65 (In Russ.)
http://www.geotar.ru/lots/NF0005151.html
3. Martillo MA, Nazzal L, Crittenden DB. The crystallization of monosodium urate. Curr Rheumatol Reports. 2014;16(2):400. doi: 10.1007/s11926-013-0400-9
4. Richette P, Doherty M, Pascual Е, et al. 2018 updated European League Against Rheumatism evidence-based recommendations for the
diagnosis of gout. Ann Rheum Dis. 2019;79(1):31-8. doi: 10.1136/
annrheumdis-2019-215315
5. Ragab G, Elshahaly M, Bardin T. Gout: An old disease in new perspective – A review. J Advanc Res. 2017;8(5):495-511. doi: 10.1016/j.jare.2017.04.008
6. Choi HK, Atkinson K, Karlson EW, Curhan G. Purine-rich foods, dairy and protein intake, and the risk of gout in men. New Engl J Med. 2004;350(11):1093-103. doi: 10.1056/nejmoa035700
7. Zhang Y, Woods R, Chaisson CE, et al. Alcohol consumption as a trigger of recurrent gout attacks. Am J Med. 2006;119(9):800.e11-800.e16. doi: 10.1016/j.amjmed.2006.01.020
8. Choi HK, Atkinson K, Karlson EW, Curhan G. Obesity, weight change, hypertension, diuretic use, and risk of gout in men: the health professionals follow-up study. Arch Intern Med. 2005;165(7):742-8. doi: 10.1001/archinte.165.7.742
9. Hootman JM, Helmick CG. Projections of US prevalence of arthritis and associated activity limitations. Arthrit Rheumatol. 2006;54:226-9. doi: 10.1002/art.21562
10. Newberry SJ, FitzGerald JD, Motala A, et al. Diagnosis of Gout: A Systematic Review in Support of an American College of Physicians Clinical Practice Guideline. Arch Intern Med. 2017;166(1):27-36. doi: 10.7326/M16-0462
11. Rees F, Jenkins W, Doherty M. Patients with gout adhere to curative treatment if informed appropriately: proof-of-concept observational study. Ann Rheum Dis. 2013;72:826-30. doi: 10.1136/annrheumdis-2012-201676
12. De Vera MA, Marcotte G, Rai S, et al. Medication adherence in gout: asystematic review. Arth Care Res. 2014;66(10):1551-9. doi: 10.1002/acr.22336
13. Yin R, Li L, Zhang G, et al. Rate of adherence to urate-loweringtherapy among patients with gout: a systematic review and meta-analysis. BMJ Open. 2018;8(4):e017542. doi: 10.1136/bmjopen-2017-017542
14. Richette P, Doherty M, Pascual E, et al. Updated EULAR evidence-based recommendations for the management of gout. Ann Rheum Dis. 2016;76(1):29-42. doi: 10.1136/annrheumdis-2016-209707
15. Tsurko VV, Gromova MA. A rationally grounded approach to treating gout with regard to its onset and course and the presence of comorbidity according to the European League against Rheumatism (EULAR 2016) recommendations. Therapeutic Archive. 2017;89(12):233-7 (In Russ.) doi: 10.17116/terarkh20178912233-237
16. Becker MA, MacDonald PA, Hunt BJ, et al. Determinants of the clinical outcomes of gout during the first year of urate-lowering therapy. Nucleosides, Nucleotides Nucleic Acids. 2008;27:585-91. doi: 10.1080/15257770802136032
17. Wortmann RL, Macdonald PA, Hunt B, Jackson RL. Effect of prophylaxis on gout flares after the initiation of urate-lowering therapy: analysis of data from three phase III trials. Clin Ther. 2010;32:2386-97. doi: 10.1016/j.clinthera.2011.01.008
18. Kydd AS, Seth R, Buchbinder R, et al. Uricosuric medications for chronic gout. Cochrane Database System Rev. 2014;(11):CD01045. doi: 10.1002/14651858.cd010457.pub2
19. Hira D, Chisaki Y, Noda S, et al. Population pharmacokinetics and therapeutic efficacy of febuxostat in patients with severe renal impairment. Pharmacology. 2015;96:90-8. doi: 10.1159/000434633
20. Neogi T. Gout. Ann Intern Med. 2016;165(1):ITC1-ITC16. doi: 10.7326/AITC201607050
21. Finkelstein Y, Aks SE, Hutson JR, et al. Colchicine poisoning: the dark side of an ancient drug. Clin Toxicol. 2010;48:407-14. doi: 10.3109/15563650.2010.495348
22. Keenan RT, O’Brien WR, Lee KH, et al. Prevalence of contra indications and prescription of pharmacologic therapies for gout. Am J Med. 2011;124:155-63. doi: 10.1016/j.amjmed.2010.09.012
23. Asghar W, Jamali F. The effect of COX-2-selective meloxicam on the myocardial, vascular and renal risks: a systematic review. Inflammopharmacol. 2015;23(1):1-16. doi: 10.1007/s10787-014-0225-9
24. Yang M, Wang HT, Zhao M, et al. Network Meta-Analysis Comparing Relatively Selective COX-2 Inhibitors Versus Coxibs for the Prevention of NSAID-Induced Gastrointestinal Injury. Medicine. 2015;94(40):e1592. doi: 10.1097/md.0000000000001592
25. Arfè A, Scotti L, Varas-Lorenzo C, et al. Non-steroidal anti-inflammatory drugs and risk of heart failure in four European countries: nested case-control study. BMJ. 2016:i4857. doi: 10.1136/bmj.i4857
26. Varas-Lorenzo C, Riera-Guardia N, Calingaert B, et al. Myocardial infarction and individual nonsteroidal anti-inflammatory drugs meta-analysisof observational studies. Pharmacoepidemiol Drug Safety. 2013;22(6):559-70. doi: 10.1002/pds.3437
27. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J. 2018 Sep 1;39(33):3021-104. doi: 10.1093/eurheartj/
ehy339, published 25.08.2018
28. 2019 ESC Guidelines for the Diagnosis and Management of Chronic Coronary Syndromes: The Task Force for the Diagnosis and Management of Chronic Coronary Syndromes of the European Society of Cardiology (ESC). Eur Heart J. 2020;41(3):407-77. doi: 10.1093/eurheartj/ehz425
29. Roglic G, Norris SL. Medicines for treatment intensification in type 2 diabetes and type of insulin in type 1 and type 2 diabetes in low-resource settings: Synopsis of the World Health Organization guidelines on second- and third-line medicines and type of insulin for the control of blood glucose levels in nonpregnant adults with diabetes mellitus. Ann Intern Med. 2018;169(6):394. doi: 10.7326/M18-1149
30. Humphrey LL, Kansagara D, Qaseem A, for the High Value Care Committee of the American College of Physicians. World Health Organization guidelines on medicines for diabetes treatment intensification: Commentary from the American College of Physicians high value care committee. Ann Intern Med. 2018;169(6):398. doi: 10.7326/M18-1148
31. National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification and Stratification. Am J Kidney Dis. 2002;39(Suppl. 1):1-266. https://www.ncbi.nlm.nih.gov/pubmed/11904577
32. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. 2013. https://kdigo.org/wp-content/uploads/2017/02/KDIGO_2012_CKD_GL.pdf
33. Wittens C, Davies AH, Bækgaard N, et al. Editor's Choice – Management of Chronic Venous Disease: Clinical Practice Guidelines of the European Society for Vascular Surgery (ESVS). Eur J Vasc Endovasc Surg. 2015;49(6):678-737. doi: 10.1016/j.ejvs.2015.02.007
34. Hawker GA, Mian S, Kendzerska T, French M. Measures of adult pain: Visual Analog Scale for Pain (VAS Pain), Numeric Rating Scale for Pain (NRS Pain), McGill Pain Questionnaire (MPQ), Short-Form McGill Pain Questionnaire (SF-MPQ), Chronic Pain Grade Scale (CPGS), Short Form-36 Bodily Pain Scale (SF-36 BPS), and Measure of Intermittent and Constant Osteoarthritis Pain (ICOAP). Arth Care Res. 2011;63(Suppl. 11):S240-S252. doi: 10.1002/acr.20543
35. McLeod S. Likert Scale Definition, Examples and Analysis. 2019. https://www.simplypsychology.org/likert-scale.html.
36. Amirdjanova VN, Erdes SF. Validation of general questionnaire EuroQol-5D (EQ-5D). Nauchno-prakticheskaya revmatologiya. 2007;45(3):69-76 (In Russ.) doi: 10.14412/1995-4484-2007-691
1 ФГАОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава России, Москва, Россия;
2 ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет), Москва, Россия
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M.A. Gromova1, V.V. Tsurko1,2, O.A. Kislyak1, N.V. Malysheva1
1 Pirogov Russian National Research Medical University, Moscow, Russia;
2 Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia