Rheumatoid arthritis: A major symptom and symptomatic therapy

Pain is a major problem in patients with rheumatoid arthritis (RA). It produces a serious psychological discomfort, causes sleep disorders, and drastically limits physical activity. Pain is one of the main signs of inflammation and its intensity correlates with inflammatory activity. The early use of disease-modifying antirheumatic drugs, regular monitoring, and timely correction of therapy in accordance with the treat-to-target principle make it possible to effectively monitor the activity of RA and to delay its progression. However, despite a marked decrease in RA activity, pain does not go away completely and may increase with time in a number of cases. Pain occurring in patients with RA is always far short of being caused by arthritis. It may be also related to comorbidity, osteoarthritis or fibromyalgia in particular. Pain induced by comorbidity may seriously distort the result of assessment of inflammatory activity and a physician's decision made to correct drug therapy in accordance with the treat-to-target principle.

Nonsteroidal antiinflammatory drugs (NSAIDs) are in most common use for the symptomatic therapy of RA. In spite of a significant reduction in pain and stiffness during therapy with NSAIDs, they do not affect the progression of X-ray changes. Virtually all NSAIDs may relieve pain when used in doses substantially smaller than those required to suppress inflammation. NSAIDs are an essential component of combination therapy for RA. They are given just at the early stage of the disease, by taking into account the gastrointestinal tract, kidney, and cardiovascular system. The National Institute for Health and Clinical Excellence in the United Kingdom proposes to administer analgesics (paracetamol and codeine) to reduce needs for NSAIDs in RA. For the time being, the use of analgesics in RA has, however, a weak evidence base.

Different trials have also studied the efficiency of monotherapy with weak opioids, but it has proven to be also low. It is well, where possible, to avoid the long-term use of opioids.

Along with NSAIDs and paracetamol, the recent guidelines of the International Expert Group of Pain Pharmacotherapy to use tricyclic antidepressants as additional agents to treat joint inflammatory diseases, which may be effective in some cohort of patients, such as those with RA and comorbid depressive disorders.

Besides drug therapy, nonpharmacological methods are also successfully used in the treatment of pain in RA. The effective suppression of pain makes it possible not only to considerably reduce existing discomfort in a patient, but also to more correctly choose treatment policy in each specific case.

1. Каратеев ДЕ, Лучихина ЕЛ, Тюрина ЛН и др. Возможности ранней диагностики ревматоидного артрита в клинической практике на современном этапе (результаты наблюдений за московской когортой больных ранним артритом в рамках программы РАДИКАЛ). Терапевтический архив. 2008;80(5):8–13. [Karateev DE, Luchikhina EL, Tyurina LN, et al. Possibilities of early diagnosis of rheumatoid arthritis in clinical practice at the present stage (results of supervision over the Moscow cohort of patients with early arthritis within the RADICAL program). Terapevticheskii arkhiv. 2008;80(5):8–13. (In Russ.)].

2. Бестаев ДВ. Каратеев ДЕ, Насонов ЕЛ. Системные проявления ревматоидного артрита. Научно-практическая ревматология. 2013;51(1):76–80. [Bestaev DV. Karateev DE, Nasonov EL. Systemic manifestations of rheumatoid arthritis. Nauchnoprakticheskaya revmatologiya = Rheumatology Science and Practice. 2013;51(1):76–80. (In Russ.)]. DOI: http://dx.doi.org/10.14412/1995-4484-2013-1206.

3. Амирджанова ВН. Качество жизни больных ревматоидным артритом, получающих ритуксимаб. Научно-практическая ревматология. 2008;(1S):15–20. [Amirdzhanova VN. Kachestvo zhizni bol'nykh revmatoidnym artritom, poluchayushchikh rituksimab. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice. 2008;(1S):15–20. (In Russ.)]. DOI: http://dx.doi.org/10.14412/1995-4484-2008-3.

4. Зелтынь АЕ, Фофанова ЮС, Лисицына ТА и др. Хронический стресс и депрессия у больных ревматоидным артритом. Социальная и клиническая психиатрия. 2009;19(2):69–75. [Zeltyn' AE, Fofanova YuS, Lisitsyna TA, et al. Chronic stress and depression in patients with rheumatoid arthritis. Sotsial'naya i klinicheskaya psikhiatriya. 2009;19(2):69–75. (In Russ.)]

5. Вакуленко ОЮ, Горячев ДВ, Кричевская ОА, Эрдес ШФ. Оценка снижения производительности труда у больных ревматоидным артритом. Научно-практическая ревматология. 2013;51(6):671–9. [Vakulenko OYu, Goryachev DV, Krichevskaya OA, Erdes ShF. Evaluation of a decrese in work productivity in patients with rheumatoid arthritis. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice. 2013;51(6):671–9. (In Russ.)]. DOI: http://dx.doi.org/10.14412/1995-4484-2013-671-9.

6. Каратеев ДЕ, Лучихина ЕЛ, Муравьев ЮВ и др. Первое российское стратегическое исследование фармакотерапии ревматоидного артрита (РЕМАРКА). Научно-практическая ревматология. 2013;51(2):117–25. [Karateev DE, Luchikhina EL, Murav'ev YuV, et al. The first Russian strategic study of pharmacotherapy for rheumatoid arthritis (REMARCA). Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice. 2013;51(2):117–25. (In Russ.)]. DOI: http://dx.doi.org/10.14412/1995-4484-2013-637.

7. Atzeni F, Cazzola M, Benucci M, et al. Chronic widespread pain in the spectrum of rheumatological diseases. Best Pract Res Clin Rheumatol. 2011 Apr;25(2):165–71. DOI: http://dx.doi.org/10.1016/j.berh.2010.01.011.

8. Эрдес ШФ, Галушко ЕА. Частота фибромиалгии (ФМ) среди пациентов с хронической распространенной болью (ХРБ) V съезд ревматологов России. Сборник материалов Съезда (тезисы). Москва; 2009. 132 c. [Erdes ShF, Galushko EA. Chastota fibromialgii (FM) sredi patsientov s khronicheskoi rasprostranennoi bol'yu (KhRB) V s"ezd revmatologov Rossii. Sbornik materialov S"ezda (tezisy) [Frequency of a fibromialgiya (FM) among patients with the chronic widespread pain (CWP) the V congress of rheumatologists of Russia. Collection of materials of Congress (theses)]. Moscow; 2009. 132 p.]

9. Schaible HG, von Banchet GS, Boettger MK, et al. The role of proinflammatory cytokines in the generation and maintenance of joint pain. Ann N Y Acad Sci. 2010 Apr;1193:60–9. DOI: http://dx.doi.org/10.1111/j.1749-6632.2009.05301.x.

10. Benemei S, Nicoletti P, Capone JG, Geppetti P. CGRP receptors in the control of pain and inflammation. Curr Opin Pharmacol. 2009 Feb;9(1):9–14. DOI: http://dx.doi.org/10.1016/j.coph.2008.12.007.

11. Richter F, Natura G, Lö ser S, et al. Tumor necrosis factor causes persistent sensitization of joint nociceptors to mechanical stimuli in rats. Arthritis Rheum. 2010 Dec;62(12):3806–14. DOI: http://dx.doi.org/10.1002/art.27715.

12. Lee YC. Effect and treatment of chronic pain in inflammatory arthritis. Curr Rheumatol Rep. 2013 Jan;15(1):300. DOI: http://dx.doi.org/10.1007/s11926-012-0300-4.

13. Насонова ЕЛ, Насоновой ВА, редакторы. Ревматология. Национальное руководство, Москва: ГЭОТАР-Медиа. 2008. 714 c. [Nasonov EL, Nasonova VA, editors. Revmatologiya. Natsional'noe rukovodstvo [Rheumatology. National Guide]. Moscow: GEOTAR-media; 2008. 714 p.]

14. Khanna D, Ranganath VK, Fitzgerald J, et al. Increased radiographic damage scores at the onset of seropositive rheumatoid arthritis in older patients are associated with osteoarthritis of the hands, but not with more rapid progression of damage. Arthritis Rheum. 2005 Aug;52(8):2284–92. DOI: http://dx.doi.org/10.1002/art.21221.

15. Edwards RR, Cahalan C, Mensing G, et al. Pain, catastrophizing, and depression in the rheumatic diseases. Nat Rev Rheumatol. 2011 Apr;7(4):216–24. DOI: http://dx.doi.org/10.1038/nrrheum.2011.2.

16. Rupp I, Boshuizen HC, Dinant HJ, et al. Disability and health-related quality of life among patients with rheumatoid arthritis: association with radiographic joint damage, disease activity, pain, and depressive symptoms. Scand J Rheumatol. 2006 May–Jun;35(3):175–81. DOI: http://dx.doi.org/10.1080/03009740500343260.

17. Филатова ЕС, Алексеев ВВ, Эрдес ШФ. Болевой синдром при ревматоидном артрите. Научно-практическая ревматология 2011;(6):32–5. [Filatova ES, Alekseev VV, Erdes ShF. Pain syndrome in rheumatoid arthritis. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice. 2011;(6):32–5. (In Russ.)]. DOI: http://dx.doi.org/10.14412/1995-4484-2011-517.

18. Sokka T, Toloza S, Cutolo M, et al. Women, men, and rheumatoid arthritis: analyses of disease activity, disease characteristics, and treatments in the QUEST-RA study. Arthritis Res Ther. 2009;11(1):R7.

19. Hinz B, Brune K. Antipyretic analgesics: nonsteroidal antiinflammatory drugs, selective COX-2 inhibitors, paracetamol and pyrazolinones. Handb Exp Pharmacol. 2007;(177):65–93.

20. Каратеев АЕ, Яхно НН, Лазебник ЛБ и др. Применение нестероидных противовоспалительных препаратов. Москва: ИМА-ПРЕСС; 2009. 167 с. [Karateev AE, Yakhno NN, Lazebnik LB, et al. Primenenie nesteroidnykh protivovospalitel'nykh preparatov. Moscow: IMA-PRESS; 2009. 167 p.]

21. Greenberg JD, Fisher MC, Kremer J, et al. The COX-2 inhibitor market withdrawals and prescribing patterns by rheumatologists in patients with gastrointestinal and cardiovascular risk. Clin Exp Rheumatol. 2009 May–Jun;27(3):395–401.

22. Ito S, Okuda-Ashitaka E, Minami T. Central and peripheral roles of prostaglandins in pain and their interactions with novel neuropeptides nociceptin and nocistatin. Neurosci Res. 2001 Dec;41(4):299–332. DOI: http://dx.doi.org/10.1016/S0168-0102(01)00289-9.

23. Hochberg MC. New directions in symptomatic therapy for patients with osteoarthritis and rheumatoid arthritis. Semin Arthritis Rheum. 2002 Dec;32(3 Suppl 1):4–14. DOI: http://dx.doi.org/10.1053/sarh.2002.37215.

24. Martin-Mola E, Gijon-Banos J, Ansoleaga JJ. Aceclofenac in comparison to ketoprofen in the treatment of rheumatoid arthritis. Rheumatol Int. 1995;15(3):111–6. DOI: http://dx.doi.org/10.1007/BF00302127.

25. Каратеев АЕ, Денисов ЛН, Маркелова ЕИ и др. Результаты клинического исследования АЭРОПЛАН (анализ эффективности и риска осложнений при лечении артрита ацеклофенаком и нимесулидом). Consilium medicum. 2013;15(2):52–7. [Karateev AE, Denisov LN, Markelova EI, et al. Results of clinical trial the AIRPLANE (the analysis of efficiency and risk of complications at treatment of arthritis atseklofenaky and nimesulidy). Consilium medicum. 2013;15(2):52–7. (In Russ.)].

26. Helin-Salmivaara A, Virtanen A, Vesalainen R, et al. NSAID use and the risk of hospitalization for first myocardial infarction in the general population: a nationwide case-control study from Finland. Eur Heart J. 2006 Jul;27(14):1657–63. DOI: http://dx.doi.org/10.1093/eurheartj/ehl053.

27. National Institute for Health and Care Excellence (NICE) Rheumatoid arthritis – the management of rheumatoid arthritis in adults. Clinical guidelines. CG79 – Issued: February 2009. London: HMSO; 2009.

28. Marks JL, Colebatch AN, Buchbinder R, Edwards CJ. Pain management for rheumatoid arthritis and cardiovascular or renal comorbidity. Cochrane Database Syst Rev. 2011 Oct 5;(10):CD008952.

29. Lee EY, Lee EB, Park BJ, et al. Tramadol 37.5-mg/acetaminophen 325-mg combination tablets added to regular therapy for rheumatoid arthritis pain: a 1-week, randomized, double-blind, placebo-controlled trial. Clin Ther. 2006 Dec;28(12):2052–60. DOI: http://dx.doi.org/10.1016/j.clinthera. 2006.12.019.

30. Whittle SL, Richards BL, Husni E, Buchbinder R. Opioid therapy for treating rheumatoid arthritis pain. Cochrane Database Syst Rev. 2011 Nov 9;(11):CD003113.

31. Crofford LJ. Adverse effects of chronic opioid therapy for chronic musculoskeletal pain. Nat Rev Rheumatol. 2010 Apr;6(4):191–7. DOI: http://dx.doi.org/10.1038/nrrheum.2010.24.

32. Whittle SL, Colebatch AN, Buchbinder R, et al. Multinational evidencebased recommendations for pain management by pharmacotherapy in inflammatory arthritis: integrating systematic literature research and expert opinion of a broad panel of rheumatologists in the 3e Initiative. Rheumatology (Oxford). 2012 Aug;51(8):1416–25. DOI: 10.1093/rheumatology/kes032. Epub 2012 Mar 24.

33. Яльцева НВ, Григорьева ЕА, Коршунов НИ. Применение антидепрессантов у больных ревматоидным артритом с коморбидной депрессией. Научно-практическая ревматология. 2009;(1):43–9. [Yal'tseva NV, Grigor'eva EA, Korshunov NI. Antidepressants administration in rheumatoid arthritiswith comorbid depression. Nauchnoprakticheskaya revmatologiya =Rheumatology Science and Practice. 2009;(1):43–9. (In Russ.)]. DOI: http://dx.doi.org/10. 412/1995-4484-2009-141.