Clarithromycin in rheumatoid arthritis: the addition to methotrexate and low-dose methylprednisolone induces a significant additive value--a 24-month single-blind pilot study.

UNLABELLED: 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.

Clodronate and hydroxychloroquine in erosive osteoarthritis: a 24-month open randomized pilot study.

We evaluated the efficacy of clodronate for treating active erosive osteoarthritis of the hand and to compare it with hydroxychloroquine. Group A consisted of 24 patients treated for 24 months with clodronate 300 mg i.v. for 7 days, followed by clodronate i.m. 100 mg for 14 days every 3 months. Group B comprised 14 patients treated with hydroxychloroquine 400 mg daily for 30 days, followed by 200 mg daily for the next 11 months. In group A, 21/24 patients completed the trial and obtained significant pain reduction (p < 0.001), Dreiser's score (p = 0.012), and number of tender joints (p = 0.011). Strength of right (p = 0.04) and left (p = 0.016) hands, physician's global assessment (p ≤ 0.001), and patient's global assessment (p = 0.021) improved. In group B, 8/14 patients completed 12 months of the study, which showed the inefficacy of hydroxychloroquine and its lack of acceptance by patients (worsening pain and patient's global assessment). Therefore, enrolment was stopped. Differences between groups showed a pain decreasing trend for group A and a slightly increasing one for group B (p = 0.018). Physician and patient global assessments showed a strong increase in group A compared with group B (p < 0.001). Clodronate is effective in erosive osteoarthritis; hydroxychloroquine seems to be ineffective.

Complete clinical and functional recovery following low-dose methotrexate related paraparesis in a patient with compound c.1298A>C AND c.677C>T MTHFR polymorphism: A case report.

RATIONALE: The mechanisms of action of MTX (methotrexate) in the treatment of RA (rheumatoid arthritis) and PsA (psoriatic arthritis) is related to its antifolic activity, due to the high affinity for enzymes that require folate cofactors as dihydrofolate reductase and to the anti-inflammatory activity derivated from the inhibition of thymidylate synthetase that leads to the over-production of adenosine. PATIENT CONCERNS: Our patient was a 41-year-old female, affected by PsA in treatment since 2 years with low-dose methylprednisolone and low-dose subcutaneous MTX. The treatment was effective. The patient subacutely developed a severe paraparesis with impossibility of gait or standing without aid and was admitted to a Neurology Department where the cause of the paraparesis was not clear in spite of accurate radiological neurophysiologic and laboratory tests. Therefore, she was admitted in a rehabilitation unit. DIAGNOSIS AND INTERVENTIONS: Paraparesis in PsA patient in treatment with methotrexate. MTX toxicity was hypothesized; therefore the drug was discontinued while i.m. folic acid and cyanocobalamin were administered for 20 days. The diagnosis was clinical, based on neurological examination (paraparesis) and on the chronic use of MTX (hypothesis of toxicity). OUTCOMES: The patient obtained a complete resolution of paraparesis. Genetic analyses showed associated a compound heterozygosity for the c.1298A>C and c.677C>T variants of methylenetetrahydrofolate reductase (MTHFR) gene. LESSONS: Neurological side effects of MTX are uncommon. In literature no previous case of MTX induced paraparesis in patients treated with low-dose MTX for chronic arthritis has been described. The association between the gene polymorphisms of MTHFR (c.1298A>C and c.677C>T) and MTX toxicity in arthritis patients is confirmed. The case also confirms that folates are a precious antidote of MTX toxicity.

Correction to: Intramuscular clodronate in erosive osteoarthritis of the hand is effective on pain and reduces serum COMP: a randomized pilot trial-The ER.O.D.E. study (ERosive Osteoarthritis and Disodium-clodronate Evaluation).

One of the author names on this article was incorrectly tagged during the article mark-up; Luca Dalle Carbonare's name has now been correctly tagged, with first name 'Luca' and last name 'Dalle Carbonare'.

Intramuscular clodronate in erosive osteoarthritis of the hand is effective on pain and reduces serum COMP: a randomized pilot trial-The ER.O.D.E. study (ERosive Osteoarthritis and Disodium-clodronate Evaluation).

We evaluated the efficacy and safety of intramuscular clodronate (CLO) for the treatment of active erosive osteoarthritis of the hand (EOA). Forty outpatients treated with anti-inflammatory (NSAIDs) or analgesic drugs since at least 6 months, for at least 3 days a week, were randomly divided into two groups. Group A: 24 patients treated for 6 months with intramuscular (i.m.) CLO added to usual NSAIDs or analgesic drugs. The attack dose was 200 mg/day i.m. for 10 days followed by a maintenance dose of CLO i.m. 200 mg/day for 6 days after 3 and 6 months. Group B: 16 patients who continued the usual treatment with anti-inflammatory or analgesic drugs. Patients in both groups reported in a diary, day by day, the consumption of symptomatic drugs. In group A, the consumption of anti-inflammatory or analgesic drugs (p < 0.0001), pain (p < 0.0001), number of tender joints (p = 0.0097), number of swollen joints (p = 0.0251), Dreiser score (p = 0.0119), and patient's and physician's global assessment of disease activity significantly decreased (both p < 0.001). At 6 months, serum COMP also significantly decreased (p < 0.0029). Strength of right (p = 0.0465) and left hand (+38%, p = ns) significantly increased. In group B, there was no significant change in all parameters considered. Intramuscular CLO in EOA of the hand is effective and safe on pain with a significant reduction in the consumption of anti-inflammatory or analgesic drugs, increasing the functionality of the hands. Serum COMP reduction suggests that CLO could play a role as a disease-modifying drug (EudraCT number 2013-000832-85).

Densitometric evaluation might prevent failure of knee artroplasty for aseptic loosening. An 8-year observational controlled study.

OBJECTIVES: To study the correlation between quantitative ultrasound (QUS) expressed as stiffness index (SI) and the risk of aseptic loosening of knee arthroplasty.  METHODS: An observational retrospective controlled study was performed on 85 female patients (mean age: 73.3 years) divided into 2 groups from January 2007 to March 2015 and carried out at the Orthopedic Rehabilitation Unit, Casa di Cura Eremo, Arco, Trento, Italy. Group A included 42 patients who had undergone a revision of knee prosthesis for aseptic-loosening, and group B included 43 age-matched patients who underwent primary replacement of the knee without following aseptic loosening. Patients in both groups were evaluated for SI with Achilles - QUS system at the same side of the surgery. RESULTS: In group A, 20/42 patients (47.6%) had an SI T-score below -2.5. In group B, 14/43 (32.5%) patients had a SI T-score below -2.5. The difference between the 2 groups was statistically significant (p=0.015).  CONCLUSION: Stiffness index appears to be an important predictor of aseptic loosening of the knee prosthesis. Therefore, densitometric evaluation, including SI, may be recommended before surgical knee replacement.

Thiol antioxidants inhibit the formation of the interleukin-12 heterodimer: a novel mechanism for the inhibition of IL-12 production.

IL-12 is a 75 kDa heterodimeric cytokine composed of two disulfide-linked subunits, p35 and p40, which plays an important role in the regulation of the immune response. We tested the hypothesis that thiol antioxidants might interfere with dimerization of the two IL-12 subunits. We thus studied the effect of reduced glutathione (GSH) and N-acetyl-cysteine (NAC) on IL-12 p75 production by human THP-1 cell stimulated with IFN-gamma and Staphylococcus aureus Cowan strain I (SAC), using ELISAs specific for IL-12 p75 or the p40 subunit. NAC and GSH, but not cystine, at concentrations of 5-10 mM inhibited production of IL-12 p75 but not of the p40 subunit. NAC did not inhibit p40 or p35 mRNA expression in dendritic cells or THP-1 cells, or NF-kappa B activation in THP-1 cells. The effect of NAC was specific for IL-12 p75, as NAC did not affect induction of MHC class II expression by IFN-gamma-stimulated THP-1 cells. IL-12 dimer formation appears to be reduced by NAC also in vivo, because pretreatment with NAC (1 g/kg, orally), before LPS injection in mice, inhibited peak IL-12 p75 serum levels without affecting those of p40. We conclude that thiol levels regulate IL-12 p75 production and that assembly of the heterodimer is a step that might represent a target for pharmacological intervention.