Abstract
To compare the efficacy of the addition of clarithromycin (CM) to methotrexate (MTX) and methylprednisolone (MP) in active rheumatoid arthritis (RA). 32 patients with RA consecutively randomized. Control group: sixteen patients treated for 24 months with MTX 10–15 mg i.m. weekly and MP 4–6 mg daily. CM group: sixteen patients treated with MTX 10–15 mg i.m. weekly and MP 4–6 mg daily for 24 months; CM therapy added in the first month (500 mg twice a day for the first 15 days followed by 500 mg a day for the remaining 15 days). Evaluation of the improvement following ACR criteria was performed at months 1 (primary endpoint), 3 and 6. Patients were furthermore observed after 12, 18 and 24 months from the study beginning. At month 1, following ACR70 improvement criteria, we found a significant additive value in CM group (10/16 = 63 % vs 4/16 = 25 %, p = 0.033—chi-square test). After discontinuation of CM, the difference between groups was anymore evident (month 3: CM group 10/16 = 63 % vs control group 9/16 = 56 %). At month 24, 7/16 (44 %) in control group and 12/16 (75 %) in CM group completed the follow-up. The addition of CM to MTX and MP can induce the remission ACR 70 in the majority of RA patients within 4 weeks, while MTX and MP alone need about 3 months to achieve the same result.
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Ianaro A, Ialenti A, Maffia P, Sautebin L, Rombolà L, Carnuccio R et al (2000) Anti-inflammatory activity of macrolide antibiotics. J Pharmacol Exp Ther 292:156–163
Saviola G, Abdi-Ali L, Rossini P, Campostini L, Coppini A, Gori M et al (2002) Clarithromycin in rheumatoid arthritis patients not responsive to disease-modifying anti-rheumatic drugs: an open uncontrolled pilot study. Clin Exp Rheum 20:373–378
Ogrendik M (2007) Effects of clarithromycin in patients with active rheumatoid arthritis. Curr Med Res Opin 23:515–522
Moskowitz R, Lesko M, Hooper M (2006) Open-label study of clarithromycin in patients with undifferentiated connective tissue disease. Semin Arthritis Rheum 36:82–87
Saviola G, Benucci M, Abdi Ali L, Baiardi P, Manfredi M, Bucci MR et al (2010) Clarithromycin in adult onset Still’s disease. A study of 6 cases. Rheumatol Int 30(4):555–560. (Epub 2009 Dec 23)
Lequerré T, Quartier P, Roselini D et al (2008) Interleukin-1 receptor antagonist (anakinra) treatment in patients with systemic-onset juvenile idiopathic arthritis or adult onset Still disease: preliminary experience in France. Ann Rheum Dis 67:302–308
Saviola G, Abdi-Ali L, Shams-Eddin S, Davoli C, Taglietti M (2004) Clarithromycin in adult-onset Still’s disease. Case report with 1 year follow-up. Clin Exp Rheumatol 22:379
Thanou-Stavraki A, Aberle T, Aksentijevich I, Bane BL, Harley JB (2011) Clarithromycin in adult-onset Still’s disease: a potentially useful therapeutic. J Clin Rheumatol 17(7):373–376
Burrel RC, Walters JD (2008) Distribution of systemic clarithromycin to gingiva. J Periodontol 79:1712–1718
Schulz KF, Altman DG, Moher D (2010) CONSORT Group. CONSORT 2010 Statemen: updated guidelines for reporting parallel group randomised trials. J Clin Epidemiol 63(8):834–840
Stone M, Fortin PR, Pacheco-Tena C, Inman RD (2003) Should tetracycline treatment be used more extensively for rheumatoid arthritis? Metaanalysis demonstates clinical benefit with reduction in disease activity. J Rheumatol 30(10):2112–2122
Ogrendik M (2009) Rheumatoid arthritis is linked to oral bacteria. Mod Rheumatol 19(5):453–456. (Epub 2009 Jun 24, Review)
Tamaoki J, Kadota J, Takizawa H (2004) Clinical implications of the immunomodulatory effects of macrolides. Am J Med 117:5S–11S
Borszcz PD, Befus D, Moqbel R, Sin DD, Adamko DJ, Man SFP et al (2005) Effects of clarithromycin on inflammatory cell mediator release and survival. Chemotherapy 51:206–210
Simpson JL, Powell H, Boyle MJ, Scott RJ, Gibson PG (2008) Clarithromycin targets neutrophilic airway inflammation in refractory asthma. Am J Respir Crit Care 177:148–155
Giamarellos-Bourboulis EJ (2008) Immunomodulatory therapies for sepsis: unexpected effects with macrolides. Int J Antimicrob Agents 32(Suppl 1):S39–S43
Morris TC, Kettle PJ, Drake M, Jones FC, Hull DR, Boyd K et al (2008) Clarithromycin with low-dose dexamethasone and thalidomide is effective in relapsed/refractory myeloma. Br J Haematol 143(3):349–354. (Epub 2008 Aug 28)
Gay F, Rajkumar SV, Coleman M, Kumar S, Mark T, Dispenzieri A, Pearse R et al (2010) Clarithromycin (Biaxin)-lenalidomide-low-dose-dexamethasone (BiRd) versus Lenalidomide-low-dose dexamethasone (Rd) for newly diagnosed myeloma. Am J Hematol 85(9):664–669
Nakamura M, Kikukawa Y, Takeya M, Mitsuya H, Hata H (2010) Clarithromycin attenuates autophagy in myeloma cells. Int J Oncol 37(4):815–820
Saviola G, Benucci M, Cirino G (2007) Comments on: effects of clarithromycin in patients with active rheumatoid arthritis. Cur Med Res Opin 23:515–522
Rugter Persson G (2012) Rheumatoid Arthritis and periodontitis-inflammatory and infectious connections. Review of the literature. J Oral Microbiol. Epub 2012 Feb 12
Tanaka Y, Suzuki K, Saito K (2007) Efficacv of tacrolimus for joint destruction in rheumatoid arthritis. Clin Calcium 17(4):593–9. Review
Bruyn GA, Tate G, Caeiro F, Maldonado-Cocco J, Westhovens R, Tannenbaum H et al. (2008) RADD Study Group. Everolimus in patients with rheumatoid arthritis receiving concomitant methotrexate: a 3–month, double blind, randomized, placebo-controlled, parallel-group, poof-of concept study. Ann Rheum Dis 67(8):1090–1095. (Epub 2007 Nov 23)
Sofroniadou S, Goldsmith D (2011) Mammalian target of rapamycin (mTOR) inhibitors: potential uses and a review of haematological adverse effects. Drug Saf 34(2):97–115
Coulston J, Balaratnam N (2005) Irreversible sensorineural hearing loss due to clarithromycin. Postgrad Med J 81:58–59
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Saviola, G., Abdi-Ali, L., Campostrini, L. et al. Clarithromycin in rheumatoid arthritis: the addition to methotrexate and low-dose methylprednisolone induces a significant additive value—a 24-month single-blind pilot study. Rheumatol Int 33, 2833–2838 (2013). https://doi.org/10.1007/s00296-013-2822-0
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DOI: https://doi.org/10.1007/s00296-013-2822-0