Preview

Tuberculosis and Lung Diseases

Advanced search

Leflunomide as a potential second-line drug in the treatment of sarcoidosis

https://doi.org/10.21292/2075-1230-2019-97-8-52-58

Abstract

Sarcoidosis is systemic granulomatosis of an unknown nature, the course of which varies from spontaneous remission to progression resulting in failure of organs and systems. The article presents a review of current approaches to treatment of sarcoidosis putting special emphasis on the use of the anti-rheumatic drug of leflunomide (LEF). LEF is a prodrug derived from isoxazole, which is rapidly converted by liver and intestinal wall into an active metabolite, A77-1726, which inhibits the biosynthesis of pyrimidine nucleotides. LEF slows down the cell cycle, inhibits the activity of the mitochondrial enzyme dihydroorotate dehydrogenase, a key enzyme in the primary (de novo) synthesis of pyrimidines used by lymphocytes for clonal expansion. There are English reports on 2 retrospective studies of LEF used to manage sarcoidosis refractory to traditional therapy and a number of descriptions of clinical cases that provided encouraging results. LEF was found to be safer than methotrexate with comparable efficacy in both rheumatoid arthritis and sarcoidosis. Literature data indicate the feasibility of studying leflunomide in clinical practice of sarcoidosis.

About the Authors

A. A. Vizel
Kazan State Medical University
Russian Federation
Aleksandr A. Vizel ‒ Doctor of Medical Sciences, Professor, Head of Department

49, Butlerova St., Kazan, 420012



I. Yu. Vizel
Kazan State Medical University; Central Tuberculosis Research Institute
Russian Federation

Irina Yu. Vizel ‒ Doctor of Medical Sciences, Associate Professor of Phthisiopulmonology Department

49, Butlerova St., Kazan, 420012



References

1. Karateev D.E., Orlova E.V. Leflunomide in the treatment of rheumatoid arthritis: what is new? Trudny Patsient, 2016, vol. 14, no. 10-11, pp. 30-39. (In Russ.)

2. Monastyrskaya E.А., Lyamina S.V., Malyshev I.Yu. M1 and M2 phenotypes of activated macrophages and their role in the immune response and pathology. Patogenez, 2008, vol. 6, no. 4, pp. 31-39. (In Russ.)

3. Muraviev Yu.V., Gridneva G.I., Muravieva L.А., Аlekseeva А.V., Nurbaeva K.S., Mikhaylov K.M., Rozov А.V. Grounds to cancel basic anti-inflammatory drugs, genetically engineered biologic drugs and tofacitinib in case of rheumatoid arthritis. Sovr. Revmatologiya, 2018, vol. 11, no. 4, pp. 101-105. (In Russ.)

4. Novikov P.I., Burnevich E.Z., Tikhonova N.Yu., Moiseev S.V. Hepatotoxicity of anti-rheumatoid drugs. Klinicheskaya Farmakologiya i Terapiya, 2013, vol. 22, no. 5, pp. 56-60. (In Russ.)

5. Olyunin Yu.А. Leflunomide in the clinical practice. Sovr. Revmatologiya, 2014, vol. 8, no. 1, pp. 59-63. (In Russ.)

6. Orlova E.V. Place of leflunomide in the contemporary treatment strategy of rheumatoid arthritis. Trudny Patsient, 2015, vol. 13, no. 30, pp. 20-27. (In Russ.)

7. Sarkaidoz. [Sarcoidosis]. Vizel A.A. eds., Chuchalin A.G., eds., Moscow, Izdatelsky Kholding Atmosfera Publ., 2010, 416 p.

8. Sologova S.S., Chubarev V.N., Maksimov M.L., Grigorevskikh E.M., Lapkina N.А. Basic anti-rheumatoid drugs: a view of the clinical pharmacologist. Ross. Med. Journal, 2017, vol. 25, no. 14, pp. 1033-1038. (In Russ.)

9. Adler B.L., Wang C.J., Bui T.L., Schilperoort H.M., Armstrong A.W. Anti-tumor necrosis factor agents in sarcoidosis: A systematic review of efficacy and safety. Semin. Arthritis Rheum., 2018, Oct 16. pii: S0049-0172(18)30381-0. doi: 10.1016/j.semarthrit.2018.10.005. [Epub ahead of print].

10. ATS/ERS/WASOG Statement on sarcoidosis. Sarcoidosis Statement Committee. American Thoracic Society. European Respiratory Society. World Association for Sarcoidosis and other Granulomatous Disorders. Eur. Respir. J., 1999, vol. 14, no. 4, pp. 735-737.

11. Au S., Mirsaeidi M., Aronson I.K., Sweiss N.J. Adalimumab induced subcutaneous nodular sarcoidosis; a rare side effect of tumor necrosis factor-α inhibitor. Sarcoidosis Vasc. Diffuse Lung Dis., 2014, vol. 31, no. 3, pp. 249-251.

12. Baughman R.P., Barriuso R., Beyer K., Boyd J., Hochreiter J., Knoet C., Martone F., Quadder B., Richardson J., Spitzer G., Valeyre D., Ziosi G. Sarcoidosis: patient treatment priorities. ERJ Open Res., 2018, vol. 4, no. 4. pii: 00141-2018. doi: 10.1183/23120541.00141-2018. eCollection 2018 Oct.

13. Baughman R.P., Lower E.E. Leflunomide for chronic sarcoidosis. Sarcoidosis Vasc. Diffuse Lung Dis., 2004, vol. 21, no. 1, pp. 43-48.

14. Bohelay G., Bouaziz J.D., Nunes H., Rybojad M., Bagot M., Petit A., Laroche L. Striking leflunomide efficacy against refractory cutaneous sarcoidosis. J. Am. Acad. Dermatol., 2014, vol. 70, no. 5, pp. e111-е113. doi: 10.1016/j jaad.2013.10.048.

15. Brito-Zerón P., Pérez-Alvarez R., Pallarés L., Retamozo S., Baughman R.P., Ramos-Casals M. SarcoGEAS-SEMI Study Group. Sarcoidosis: an update on current pharmacotherapy options and future directions. Expert. Opin. Pharmacother., 2016, vol. 17, no. 18, pp. 2431-2448.

16. Cremers J.P., Drent M., Bast A., Shigemitsu H., Baughman R.P., Valeyre D., Sweiss N.J., Jansen T.L. Multinational evidence-based World Association of Sarcoidosis and Other Granulomatous Disorders recommendations for the use of methotrexate in sarcoidosis: integrating systematic literature research and expert opinion of sarcoidologists worldwide. Curr. Opin. Pulm. Med., 2013, vol. 19, no. 5, pp. 545-561.

17. Cremers J.P., Drent M., Bast A., Shigemitsu H., Baughman R.P., Valeyre D., Sweiss N.J., Jansen T.L. Multinational evidence-based World Association of Sarcoidosis and Other Granulomatous Disorders recommendations for the use of methotrexate in sarcoidosis: integrating systematic literature research and expert opinion of sarcoidologists worldwide. Curr. Opin. Pulm. Med., 2013, vol. 19, no. 5, pp. 545-561.

18. James W.E., Baughman R. Treatment of sarcoidosis: grading the evidence. Expert Rev. Clin. Pharmacol., 2018, vol. 11, no. 7, pp. 677-687. doi: 10.1080/17512433.2018.1486706. Epub 2018 Jun 18.

19. Jamilloux Y., Cohen-Aubart F., Chapelon-Abric C., Maucort-Boulch D., Marquet A., Pérard L., Bouillet L., Deroux A., Abad S., Bielefeld P., Bouvry D., André M., Noel N., Bienvenu B., Proux A., Vukusic S., Bodaghi B., Sarrot-Reynauld F., Iwaz J., Amoura Z., Broussolle C., Cacoub P., Saadoun D., Valeyre D., Sève P.; Groupe Sarcoïdose Francophone. Efficacy and safety of tumor necrosis factor antagonists in refractory sarcoidosis: A multicenter study of 132 patients. Semin. Arthritis Rheum., 2017, vol. 47, no. 2, pp. 288-294. doi: 10.1016/j.semarthrit.2017.03.005.

20. Jung J.H., Kim J.H., Song G.G. Adalimumab-induced pulmonary sarcoidosis not progressing upon treatment with etanercept. Z. Rheumatol., 2017, vol. 76, no. 4, pp. 372-374. doi: 10.1007/s00393-016-0262-4.

21. Keen H.I., Conaghan P.G., Tett S.E. Safety evaluation of leflunomide in rheumatoid arthritis. Expert. Opin. Drug Saf., 2013, vol. 12, no. 4, pp. 581-588.

22. Kolek V., Žurková M., Lošťáková V. Sarcoidosis ‒ enigmatic disease still unresolved. Vnitr. Lek. Winter, 2018, vol. 63, no. 11, pp. 807-814.

23. Korsten P., Strohmayer K., Baughman R.P., Sweiss N.J. Refractory pulmonary sarcoidosis ‒ proposal of a definition and recommendations for the diagnostic and therapeutic approach. Clin. Pulm. Med., 2016, vol. 23, no. 2, pp. 67-75.

24. Kwon O.C., Oh J.S., Hong S., Lee C.K., Yoo B., Kim Y.G. Conventional synthetic disease-modifying antirheumatic drugs and bone mineral density in rheumatoid arthritis patients with osteoporosis: possible beneficial effect of leflunomide. Clin. Exp. Rheumatol., 2019, Feb 11. [Epub ahead of print].

25. Le V., Crouser E.D. Potential immunotherapies for sarcoidosis. Expert. Opin. Biol. Ther., 2018, vol. 18, no. 4, pp. 399-407. doi: 10.1080/14712598.2018.1427727.

26. Majithia V., Sanders S., Harisdangkul V., Wilson J.G. Successful treatment of sarcoidosis with leflunomide. Rheumatology (Oxford), 2003, vol. 42, no. 5, pp. 700-702.

27. Modrykamien A., Arrossi A., Reddy A. A 50-year-old man with stage 2 sarcoidosis with pleural involvement. J. Hosp. Med., 2009, vol. 4, no. 4, pp. E1-E3. doi: 10.1002/jhm.466.

28. Pinto P., Dougados M. Leflunomide in clinical practice. Acta Reumatol. Port., 2006, vol. 31, no. 3, pp. 215-224.

29. Raj R., Nugent K. Leflunomide-induced interstitial lung disease (a systematic review). Sarcoidosis Vasc. Diffuse Lung Dis., 2013, vol. 30, no. 3, pp. 167-176.

30. Sahoo D.H., Bandyopadhyay D., Xu M., Pearson K., Parambil J.G., Lazar C.A., Chapman J.T., Culver D.A. Effectiveness and safety of leflunomide for pulmonary and extrapulmonary sarcoidosis. Eur. Respir. J., 2011, vol. 38, no. 5, pp. 1145-1150. doi: 10.1183/09031936.00195010.

31. Sato M., Veir J.K., Legare M., Lappin M.R. A retrospective study on the safety and efficacy of leflunomide in dogs. J. Vet. Intern. Med., 2017, vol. 31, no. 5, pp. 1502-1507. doi: 10.1111/jvim.14810. Epub 2017 Aug 21.

32. Sehgal V.N., Verma P. Leflunomide: dermatologic perspective. J. Dermatolog. Treat., 2013, vol. 24, no. 2, pp. 89-95. doi: 3109/09546634.2011.595383. Epub 2011 Jul 31.

33. Vorselaars A.D., Cremers J.P., Grutters J.C., Drent M. Cytotoxic agents in sarcoidosis: which one should we choose? Curr. Opin. Pulm. Med., 2014, vol. 20, no. 5, pp. 479-487. doi: 10.1097/MCP.0000000000000078.

34. Yavuz F., Guzelkucuk U. An unusual case report of gingival overgrowth associated with the use of leflunomide. Acta Reumatol. Port., 2016, vol. 41, no. 2, pp. 171-172.


Review

For citations:


Vizel A.A., Vizel I.Yu. Leflunomide as a potential second-line drug in the treatment of sarcoidosis. Tuberculosis and Lung Diseases. 2019;97(8):52-58. (In Russ.) https://doi.org/10.21292/2075-1230-2019-97-8-52-58

Views: 1077


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2075-1230 (Print)
ISSN 2542-1506 (Online)