Rheumatoid Arthritis: Paran H

Paran D, Paran H. · Department of Rheumatology, Tel-Aviv Sourasky Medical Center, 6 Weizmann Street, Tel-Aviv 64239, Israel. · Curr Opin Investig Drugs. · Pubmed #12833652 No free full text.

Abstract: Somatostatin (SST) is a naturally occurring neuropeptide that has multiple modulatory effects on the immune system and the function of synovial cells, as well as anti-angiogenic, antiproliferative and analgesic properties. These unique and diverse properties make this naturally occurring peptide an attractive candidate for use as a therapeutic agent in immune-mediated diseases, particularly in rheumatoid arthritis (RA). In this disease, proliferation of the synovial membrane, angiogenesis and dysregulated immunological activity lead to joint erosion and destruction. Here we review the postulated modes of action of SST in animal models of inflammation, autoimmunity and RA, as well as in humans. We also discuss the wide distribution of SST and its specific receptors, and the various SST analogs available. Results of a pilot study to evaluate the effect of SST analog treatment in refractory RA is discussed, and future directions for treatment and investigation are suggested.

Paran D, Elkayam O, Mayo A, Paran H, Amit M, Yaron M, Caspi D. · Tel-Aviv Sourasky Medical Centre, Tel-Aviv University, Israel. · Ann Rheum Dis. · Pubmed #11502617 links to  free full text

Abstract: OBJECTIVE: To evaluate the efficacy and safety of a long acting somatostatin analogue in a subset of patients with refractory rheumatoid arthritis (RA). METHODS: Ten patients with active, refractory RA, who had failed to respond to at least four disease modifying antirheumatic drugs (DMARDs), were treated with monthly intramuscular injections of 20 mg of a long acting preparation of octreotide (Sandostatin-LAR) for three months. They were evaluated every two weeks in an open label pilot study. The primary measure of clinical response was the American College of Rheumatology criteria for a 20% improvement in measures of disease activity (ACR 20). RESULTS: Eight patients completed the 14 week trial, while two patients received only one or two doses of the somatostatin analogue, but were eligible for evaluation. On an intention to treat basis 6/10 patients responded: four patients met the ACR 20 criteria at weeks 6-10, while two patients continued to improve with time, and met the ACR 50 and 70 criteria respectively, at week 14. On evaluation of the 10 patients as a group, a significant improvement (p<0.05) was noted in the mean visual analogue scales of pain, doctor's and patient's global assessment of disease activity, and in the mean number of swollen joints. Adverse effects were minor: transient bloating and loose stools, an urticarial rash (n=1), and a transient increase of liver enzymes (n=1). CONCLUSION: Treatment with a long acting somatostatin analogue led to significant clinical improvement in a subset of patients with active, refractory RA. The treatment was relatively safe and well tolerated. Further large, placebo controlled studies are required to evaluate this drug as a potential DMARD for patients with RA.