Rheumatoid Arthritis: Stern R

Volpi N, Schiller J, Stern R, Soltés L. · Department of Biologia Animale, University of Modena & Reggio Emilia, Via Campi 213/d, I-41100 Modena, Italy. · Curr Med Chem. · Pubmed #19442142 No free full text.

Abstract: Hyaluronan (hyaluronic acid, HA) is a linear naturally occurring polysaccharide formed from repeating disaccharide units of N-acetyl-D-glucosamine and D-glucuronate. Despite its relatively simple structure, HA is an extraordinarily versatile glycosaminoglycan currently receiving attention across a wide front of research areas. It has a very high molar mass, usually in the order of millions of Daltons, and possesses interesting visco-elastic properties based on its polymeric and polyelectrolyte characteristics. HA is omnipresent in the human body and in other vertebrates, occurring in almost all biological fluids and tissues, although the highest amounts of HA are found in the extracellular matrix of soft connective tissues. HA is involved in several key processes, including cell signaling, wound repair and regeneration, morphogenesis, matrix organization and pathobiology. Clinically, it is used as a diagnostic marker for many disease states including cancer, rheumatoid arthritis, liver pathologies, and as an early marker for impending rejection following organ transplantation. It is also used for supplementation of impaired synovial fluid in arthritic patients, following cataract surgery, as a filler in cosmetic and soft tissue surgery, as a device in several surgical procedures, particularly as an anti-adhesive following abdominal procedures, and also in tissue engineering. This review will provide an overview of the structure and physiological role of HA, as well as of its biomedical and industrial applications. Recent advances in biotechnological approaches for the preparation of HA-based materials, and as a component of tissue scaffolding for artificial organs will also be presented.

Kogan G, Soltés L, Stern R, Gemeiner P. · Institute of Chemistry, Slovak Academy of Sciences, Bratislava, Slovakia. · Biotechnol Lett. · Pubmed #17091377 No free full text.

Abstract: Hyaluronic acid (hyaluronan, HA) is a linear polysaccharide formed from disaccharide units containing N-acetyl-D-glucosamine and glucuronic acid. It has a high molecular mass, usually in the order of millions of Daltons, and interesting viscoelastic properties influenced by its polymeric and polyelectrolyte characteristics. HA is present in almost all biological fluids and tissues. In clinical medicine, it is used as a diagnostic marker for many diseases including cancer, rheumatoid arthritis and liver pathologies, as well as for supplementation of impaired synovial fluid in arthritic patients by means of intra-articular injections. It is also used in certain ophthalmological and otological surgeries and cosmetic regeneration and reconstruction of soft tissue. Herein we present an overview of the occurrence and physiological properties of HA, as well as of the recent advances in production biotechnology and preparation of the HA-based materials for medical application.

Fleischmann R, Stern R, Iqbal I. · Radiant Research-Dallas, 5939 Harry Hines Boulevard, Suite 400, Dallas, Texas 75235-5360, USA. · Expert Opin Biol Ther. · Pubmed #15268666 No free full text.

Abstract: Anakinra (Amgen, Inc.) is a specific receptor antagonist of IL-1 that differs from naturally occurring IL-1 receptor antagonist by the presence of a methionine group. Anakinra has been shown to be of benefit in patients with active rheumatoid arthritis, either when given alone or in combination with methotrexate, as assessed by improvement in clinical signs and symptoms, decreased radiographic progression and improvement in patient function, pain and fatigue, although it appears to be effective in fewer patients than anti-TNF agents. It has a favourable safety profile as demonstrated in clinical trials. The physician and patient must be cognizant of serious infectious episodes. Many of the rare side effects seen with TNF blockers, such as tuberculosis, other opportunistic infections, worsening of congestive heart failure and the development of demyelinating disease, have not been seen in patients treated with anakinra. Anakinra should not be given in combination with anti-TNF agents.

Stern R, Wolfe F. · University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA. · J Rheumatol. · Pubmed #15290732 No free full text.

Abstract: OBJECTIVE: Infliximab is an effective anti-tumor necrosis factor (TNF) agent widely used in the treatment of rheumatoid arthritis (RA). Initially recommended at a dose of 3 mg/kg, subsequent label revisions allowed doses up to 10 mg/kg or at 4-week intervals rather than the originally suggested 8-week intervals, if clinically indicated. The doses used have implications for efficacy and costs, but no data exist for actual dose used in the US. This study evaluates the dosage and rates of increase in infliximab-treated patients with RA. METHODS: Study 1: Review of patient charts and infusion records for 394 RA patients from 2 large rheumatology practices comprising 15 rheumatologists in Dallas, Texas. Study 2: Survey of 1324 RA patients using infliximab participating in a longitudinal study of RA outcomes. Patients completed a detailed questionnaire about clinical status and infliximab use. RESULTS: The results of the 2 studies were similar: the average infliximab dose was 5 mg/kg, increasing most rapidly until the end of the first years, after which the increase was slowed. Increases > 3 mg/kg occurred in 61% of patients in Study 1 and 56% in Study 2. The 8-week treatment interval was almost universally used, and more than 95% of infusions occurred in this interval. The most common reason for increase in dose was insufficient response. Among patients who completed 4 infusions, 75% remained on therapy at 2 years after infliximab start. The average improvement in Health Assessment Questionnaire disability score was 0.28. CONCLUSION: Infliximab dose increases are common, particularly during the first year of treatment. The average dose is 5 mg/kg. Seventy-five percent of patients continue using infliximab 2 years after treatment onset.

Siva C, Eisen SA, Shepherd R, Cunningham F, Fang MA, Finch W, Salisbury D, Singh JA, Stern R, Zarabadi SA. · St. Louis VAMC (151C) and Washington University School of Medicine, 915 North Grand, St. Louis, MO 63106, USA. · Arthritis Rheum. · Pubmed #14673959 links to  free full text

Abstract: OBJECTIVE: To describe leflunomide (LEF) use in a national cohort of 3,325 veterans. METHODS: Prescriptions for LEF and 9 disease-modifying antirheumatic drugs written between October 1998 and June 2001 at all Veterans Affairs (VA) medical centers were obtained from VA national databases. RESULTS: LEF was initiated with a loading dose of 100 mg daily for 3 days in 61% of patients, and 42% of patients discontinued LEF. LEF was more likely to be discontinued if a 3-day 100-mg loading dose was prescribed, patients were younger than 44 years or older than 75 years, or reported an annual family income <$60,000. Review of medical records of 291 discontinuers revealed that the most common reasons for discontinuation were inefficacy (30%), gastrointestinal symptoms (29%), medication noncompliance or lost to followup (14%), and elevated liver enzymes (5%). CONCLUSION: LEF is relatively safe in clinical practice. The VA's national databases provide an excellent, inexpensive resource for postmarketing evaluation of rheumatologic medications.