Cytokines in chronic inflammatory arthritis. V. Mutual antagonism between interferon-gamma and tumor necrosis factor-alpha on HLA-DR expression, proliferation, collagenase production, and granulocyte macrophage colony-stimulating factor production by rheumatoid arthritis synoviocytes

The effects of a broad array of cytokines, individually and in combination, were determined on separate functions (proliferation, collagenase production, and granulocyte macrophage colony-stimulating factor [GM-CSF] production) and phenotype (expression of class II MHC antigens) of cultured fibroblast-like RA synoviocytes. The following recombinant cytokines were used: IL-1 beta, IL-2, IL-3, IL-4, IFN-gamma, tumor necrosis factor (TNF)-alpha, GM-CSF, and macrophage colony-stimulating factor (M-CSF). Only IFN-gamma induced HLA-DR (but not HLA-DQ) expression. TNF-alpha inhibited IFN-gamma-mediated HLA-DR expression (46.7 +/- 4.1% inhibition) and HLA-DR mRNA accumulation. This inhibitory effect was also observed in osteoarthritis synoviocytes. Only TNF-alpha and IL-1 increased synoviocyte proliferation (stimulation index 3.60 +/- 1.03 and 2.31 +/- 0.46, respectively). IFN-gamma (but none of the other cytokines) inhibited TNF-alpha-induced proliferation (70 +/- 14% inhibition) without affecting the activity of IL-1. Only IL-1 beta and TNF-alpha induced collagenase production (from less than 0.10 U/ml to 1.10 +/- 0.15 and 0.72 +/- 0.24, respectively). IFN-gamma decreased TNF-alpha-mediated collagenase production (69 +/- 19% inhibition) and GM-CSF production but had no effect on the action of IL-1. These data demonstrate mutual antagonism between IFN-gamma and TNF-alpha on fibroblast-like synoviocytes and suggest a novel homeostatic control mechanism that might be defective in RA where very little IFN-gamma is produced.     

Comparison of tocilizumab as monotherapy or with add-on disease-modifying antirheumatic drugs in patients with rheumatoid arthritis and inadequate responses to previous treatments: an open-label study close to clinical practice

This was an exploratory analysis comparing the safety and efficacy of tocilizumab monotherapy with those of tocilizumab in combination with disease-modifying anti-rheumatic drugs (DMARDs). Data were from a single-arm, nonrandomized, open-label, 24-week study in patients with rheumatoid arthritis in which patients with inadequate responses to DMARDs or tumor necrosis factor-α inhibitors received tocilizumab 8 mg/kg intravenously every 4 weeks plus methotrexate/other DMARD(s) combination therapy. If they were intolerant of methotrexate/other DMARD, patients received tocilizumab monotherapy. Effectiveness endpoints included American College of Rheumatology (ACR) responses (ACR20/50/70/90) and disease activity score using 28 joints (DAS28). Of 1,681 patients, 239 received tocilizumab monotherapy, and 1,442 received combination therapy. Methotrexate was the most common DMARD (79 %) used in combination therapy. The frequency of adverse events (AEs), serious AEs, and AEs leading to withdrawal were similar between tocilizumab monotherapy (82.4, 7.9, and 5.4 %, respectively) and combination therapy (76.6, 7.8, and 5.1 %, respectively). No differences in ACR20/50/70/90 responses were observed between treatment groups (66.9 %/43.5 %/23.8 %/10.0 % vs 66.9 %/47.2 %/26.8 %/8.5 %, respectively; p > 0.12 for all individual comparisons, including ACR50 propensity score analyses). The decrease in DAS28 was also similar between treatment groups (mean ± standard deviation: −3.41 ± 1.49 for tocilizumab monotherapy vs −3.43 ± 1.43 for combination therapy; p > 0.33 all analyses, including propensity score analyses). Tocilizumab had a comparable safety profile, and was similarly effective, when used as monotherapy or in combination with DMARDs in a broad population of patients with rheumatoid arthritis.

     

Systemic lupus erythematosus and tetrasomy-X

An 18-year-old woman with tetrasomy-X (48,XXXX karyotype) who developed systemic lupus erythematosus is described. This is, to our knowledge, the first recorded case of this association. The occurrence of autoimmune disorders in patients with chromosomal aberrations is discussed.     

Patient perceptions concerning pain management in the treatment of rheumatoid arthritis

Previous qualitative studies have revealed discrepancies between patients' and physicians' perceptions of rheumatoid arthritis (RA) and its treatment. Questionnaires were administered to 2795 patients with RA (756 from Europe; 2039 from the USA) to measure patients' perceptions regarding pain management in RA. Although the majority of patients reported their RA as somewhat-to-completely controlled, 75% of European and 82% of US patients reported their pain as moderate-to-severe in the previous 2 months. The majority of European (60%) and US (65%) patients reported dissatisfaction with their arthritis pain. Patients' pain levels corresponded with their disease severity. A higher percentage of patients who reported severe pain were being treated for depression than those who had moderate or mild pain. Patients in the USA rated pain relief as the top required benefit from their RA medication. A comprehensive examination of patients' perspectives regarding pain could lead to better patient care and pain management strategies.     

Launch and preliminary analysis of Hospital de La Princesa's inter-specialists biological therapies unit

We herein describe an inter-specialists unit for the monitoring and management of biological therapies and analyze the utilization of biological agents across specialties and diseases. Protocols and therapeutic objectives, as well as outcomes and protocol deviations, are shared and discussed periodically between specialists. All patients treated at one centre with any biological treatment from January 2000 by rheumatology, gastroenterology, dermatology, or neurology, regardless diagnosis, are identified by Clinical Pharmacy and included in an ongoing database that detects use and outcome. The drugs, survival, and reasons for discontinuation differ significantly across specialties. This approach has helped us recognizing the challenges and size of the problem of sharing expensive medications across specialties, and has served as a starting point to contribute to the better use of these compounds.     

Proteins responsible for anticentromere activity found in the sera of patients with CREST-associated Raynaud''s phenomenon.

Anticentromere antibodies (ACA) present in a high percentage of patients with complete or incomplete CREST scleroderma, and which are presently used in the diagnosis of this disease, also appear in some primary Raynaud's phenomenon patients. Three principal centromeric antigens, CENP-A, CENP-B and CENP-C, have been described as reacting with the sera of these individuals. We attempt to determine whether or not a correlation between the presence of ACA and serum reactivity against one or more of these peptides could be established, and have observed that CENP-A, but not CENP-B or CENP-C, is specifically recognized by all patients sera tested. The fact that this reactivity is clearly detectable at very high serum dilutions, thus eliminating other non-specific interference, suggests that anti-CENP-A activity might be useful in the diagnosis of patients with CREST-associated Raynaud's phenomenon.