Rheumatoid Arthritis: Coppini A

Saviola G, Abdi Ali L, Rossini P, Campostrini L, Coppini A, Gori M, Ianaro A, Bucci M, de Nucci G, Cirino G. · Fondazione Salvatore Maugeri IRCCS, Rheumatology Unit, Castel Goffredo, Mantua, Italy. · Clin Exp Rheumatol. · Pubmed #12102474 No free full text.

Abstract: OBJECTIVE: In 1996 we found by serendipity that 2 patients with rheumatoid arthritis (RA) who were taking clarithromycin (CM) to eradicate Helicobacter pylori experienced a regression of their RA symptoms. Following this observation, we tested the hypothesis that this reduction in symptoms could have been caused by CM administration. METHODS: We performed a 6-month, open, uncontrolled pilot study on 18 patients (14 females and 4 males, mean age 62 yrs.) with RA who had previously received DMARDs (mean 2.6) and discontinued the treatment at least one month earlier because lack of efficacy or severe side effects. Patients were treated with CM at the dose of 500 mg twice per day for the first 10 days, followed by a daily maintenance dose of 250 mg twice per day. RESULTS: 4/18 patients did not complete the treatment, 2/18 were not responsive to the treatment and 2/18 discontinued the treatment. Following ACR criteria the improvement was: 10 patients ACR 20; 6 patients ACR 50; and 2 patients ACR 70. The remaining 4 patients did not reach ACR 20 since either the number of tender or swollen joints was not to the level required. Reductions in PGE2 and soluble phospholipase A2 plasma levels were closely related to CM plasma levels. CONCLUSIONS: Ourfindings suggest that CM treatment can be beneficial in those patients who are not responsive to or cannot tolerate DMARDs. No definitive conclusions can be drawn based on the present study, due to the small sample size involved.

Saviola G, Abdi Ali L, Shams Eddin S, Coppini A, Cavalieri F, Campostrini L, Sacco S, Bucci M, Cirino G, Rossini M. · Rheumatology and Rehabilitation Unit, Salvatore Maugeri Foundation IRCCS, 46042 Castel Goffredo, Mantua, Italy. · Rheumatology (Oxford). · Pubmed #17384176 links to  free full text

Abstract: OBJECTIVE: To evaluate: (i) a correct equivalence ratio of clinical efficacy between low-dose deflazacort (DFZ) and methyl prednisolone (MP); and (ii) bone metabolic effects of low-dose DFZ and MP in the treatment of male RA and PsA. METHODS: A total of 21 male patients with active RA or PsA, naive to steroid treatment were chosen for the study. Group I: 10 patients treated for 6 months with DFZ 7.5 mg, calcium, cholecalciferol and a DMARD; for the following 6 months with MP 4 mg, calcium, cholecalciferol and a DMARD. Group II: 11 patients treated for 6 months with MP 4 mg, calcium, cholecalciferol and a DMARD; for the following 6 months with DFZ 7.5 mg, calcium, cholecalciferol and a DMARD. At day 0, 90, 180, 240 and 360 evaluation of ACR improvement criteria; a blood sample for total and bone-specific ALP, calcium, phosphorus, PTH, SHBG, estradiol, ACTH, osteocalcin, LH, OPG; a sample of urine for calcium, phosphorus, creatinine and DPD. RESULTS: 13/21 patients (6/10 Group I; 7/11 Group II) reached ACR 20 at 6 months; 14/21 (7/10 Group I, 7/10 Group II) at 12 months. Only at the third month we observed in Group II vs Group I a reduction of OPG (24% vs 6%, P = n.s.); ALP (P < 0.001) and osteocalcin (P = 0.006) decreased in both groups from the third month; DPD decreased in both groups only from the sixth month (P = 0.002). CONCLUSIONS: The correct equivalence ratio of DFZ to MP is 1.875:1, and of DFZ to prednisolone 1.5:1. We found a relative prevalence of bone resorption compared to bone formation in the first 6 months of treatment. The trend of OPG requires further investigation.

Del Rosso A, Cinelli M, Guiducci S, Pignone A, Fibbi G, Margheri F, Gabrielli A, Giacomelli R, Coppini A, Del Rosso M, Matucci Cerinic M. · Department of Internal Medicine, Division of Rheumatology, University of Florence, Viale Pieraccini 18, 50139 Firenze, Italy. · Rheumatology (Oxford). · Pubmed #15998634 links to  free full text

Abstract: OBJECTIVE: Extracellular fibrinolysis, controlled by the cell-associated fibrinolytic system (urokinase plasminogen activator, uPA; uPA receptor, uPAR; plasminogen activator inhibitor type-1, PAI-1), is involved in cartilage damage generation and in rheumatoid arthritis (RA) synovitis. Since steroids reduce the rate of radiological progression of RA, we planned to evaluate in healthy and RA synoviocytes the effects of the steroid deflazacort on uPA, uPAR and PAI-1 expression, and subsequent phenotypic modifications in terms of uPA/uPAR-dependent invasion and proliferation. METHODS: uPA, uPAR and PAI-1 levels were studied by ELISA, RT-PCR (uPAR) and zymography (uPA) in synoviocytes from four RA patients and four healthy controls. Chemoinvasion was assessed by the Boyden chamber invasion assay, using Matrigel as the invasion substrate. Proliferation was evaluated by cell counting. Both invasion and proliferation were measured upon treatment with deflazacort 5 muM with or without parallel stimulation with uPA 500 ng/ml or in the presence of monoclonal anti-uPA and anti-uPAR antibodies. RESULTS: Invasion and proliferation of RA synoviocytes require a proper functional balance of the fibrinolytic system. Both deflazacort and monoclonal antibodies against uPA and uPAR reduced expression and activity of the system, thus inhibiting invasion and proliferation. In RA synoviocytes, deflazacort induced higher PAI-1 and lower uPA and uPAR levels, as well as a decrease in uPA enzymatic activity. The levels of uPAR mRNA were concomitantly reduced, as was uPA-induced chemoinvasion. All these effects were also shown in controls, though to a lesser extent. CONCLUSIONS: Deflazacort might control RA synovial proliferation and invasion by differential modulation of single members of the fibrinolytic system.