ORIGINAL ARTICLE Clarithromycin in rheumatoid arthritis: the addition to methotrexate and low-dose methylprednisolone induces a significant additive value—a 24-month single-blind pilot study Gianantonio Saviola • Lul Abdi-Ali • Lorella Campostrini • Silvano Sacco • Paola Baiardi • Mariangela Manfredi • Maurizio Benucci • Mariarosaria Bucci • Giuseppe Cirino Received: 5 September 2012 / Accepted: 5 July 2013 Ó Springer-Verlag Berlin Heidelberg 2013 Abstract To compare the efficacy of the addition of clarithromycin (CM) to methotrexate (MTX) and methyl- prednisolone (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 sig- nificant additive value in CM group (10/16 = 63 % vs 4/16 = 25 %, p = 0.033—chi-square test). After discon- tinuation of CM, the difference between groups was any- more 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. Keywords Clarithromycin Á Methotrexate Á Rheumatoid arthritis Á Macrolide antibiotics Á Periodontopathic bacteria Introduction It is known that clarithromycin (CM) has an anti-inflam- matory action [1]; indeed, some clinical studies reported the use of CM in treating rheumatic diseases. In an open uncontrolled pilot study [2] on the use of CM in rheuma- toid arthritis (RA), eighteen patients unresponsive to dis- ease modifying anti-rheumatic drugs (DMARDs) were treated with CM for six months and successful results were obtained in 10 patients (56 %). In this study, CM showed a very rapid onset of action (10 days) as well as an ability to lower the plasma levels of soluble type II phospholipase and prostaglandin E2. More recently, CM efficacy was further confirmed in a double-blind trial versus placebo performed in 81 RA patients [3]. In 2006, Moskowitz published a report on seven patients affected by undiffer- entiated connective tissue disease who were successfully treated with CM in a 12-week open-label study. Also in this case, CM showed a very rapid onset of action [4]. In 2010, G. Saviola (&) Á L. Abdi-Ali Rheumatology and Rehabilitation Unit, Salvatore Maugeri Foundation IRCCS, Castel Goffredo, Mantua, Italy e-mail: gianantonio.saviola@fsm.it L. Campostrini Á S. Sacco Laboratory and Clinical Biochemistry Unit, Salvatore Maugeri Foundation IRCCS, Castel Goffredo, Mantua, Italy P. Baiardi Scientific Direction, Salvatore Maugeri Foundation IRCCS, Pavia, Italy M. Manfredi Immunology and Allergology Laboratory Unit, Hospital S. Giovanni di Dio, Azienda Sanitaria 10, Florence, Italy M. Benucci Rheumatology Unit, Department of Internal Medicine, Hospital S. Giovanni di Dio, Azienda Sanitaria, Florence, Italy M. Bucci Á G. Cirino Department of Experimental Pharmacology, Faculty of Pharmacy, University Federico II8, Naples, Italy 123 Rheumatol Int DOI 10.1007/s00296-013-2822-0