Biomarkers and personalised medicine in rheumatoid arthritis: a proposal for interactions between academia, industry and regulatory bodies.

in Annals of the Rheumatic Diseases (2011), 70(10), 1713-8

Rheumatoid arthritis (RA) is one of the most appropriate conditions for the application of personalised medicine as a high degree of heterogeneity has been recognised, which remains to be explained. Such ... [more ▼]

Rheumatoid arthritis (RA) is one of the most appropriate conditions for the application of personalised medicine as a high degree of heterogeneity has been recognised, which remains to be explained. Such heterogeneity is also reflected in the large number of treatment targets and options. A growing number of biologics as well as small molecules are already in use and there are promising new drugs in development. In order to make the best use of treatment options, both targeted and non-targeted biomarkers have to be identified and validated. To this aim, new rules are needed for the interaction between academia and industry under regulatory control. Setting up multi-centre biosample collections with clear definition of access, organising early, possibly non-committing discussions with regulatory authorities, and defining a clear route for the validation, qualification and registration of the biomarker-drug combination are some of the more critical areas where effective collaboration between the drug industry, academia and regulators is needed. [less ▲]

Adherence to treatment of osteoporosis: a need for study

in Osteoporosis International (2007), 18(10), 1311-1317

Adherence to anti-osteoporosis medications is currently low and is associated with poor anti-fracture efficacy. This manuscript reviews the potential design of clinical studies that aim to demonstrate ... [more ▼]

Adherence to anti-osteoporosis medications is currently low and is associated with poor anti-fracture efficacy. This manuscript reviews the potential design of clinical studies that aim to demonstrate improved adherence, with new chemical entities to be used in the management of osteoporosis. Introduction Several medications have been unequivocally shown to decrease fracture rates in clinical trials. However, in real life settings, long-term persistence and compliance to anti-osteoporosis medication is poor, hence decreasing the clinical benefits for patients. Methods An extensive search of Medline from 1985 to 2006 retrieved all trials including the keywords osteoporosis, compliance, persistence or adherence followed by a critical appraisal of the data obtained through a consensus expert meeting. Results The impact of non-adherence on the clinical development of interventions is reviewed, so that clinicians, regulatory agencies and reimbursement agencies might be better informed of the problem, in order to stimulate the necessary research to document adherence. Conclusion Adherence to therapy is a major problem in the treatment of osteoporosis. Both patients and medication factors are involved. Adherence studies are an important aspect of outcomes studies, but study methodologies are not well developed at the moment and should be improved. Performing adherence studies will be stimulated when registration authorities accept the result of these studies and include the relevant information in Sect. 5.1 of the summary of product characteristics. Reimbursement authorities might also consider such studies as important information for decisions on reimbursement. [less ▲]

Recommendations for the registration of agents used in the prevention and treatment of glucocorticoid-induced osteoporosis: updated recommendations from GREES

in Osteoporosis International (2005, March), 16(Suppl.3), 47

Strontium ranelate increases cartilage matrix formation

in Clinical Rheumatology (2001), 20

Strontium ranelate increases cartilage matrix formation.

in Journal of Bone and Mineral Research (2001), 16(2), 299-308

Based on previous studies showing that strontium ranelate (S12911) modulates bone loss in osteoporosis, it could be hypothesized that this drug also is effective on cartilage degradation in osteoarthritis ... [more ▼]

Based on previous studies showing that strontium ranelate (S12911) modulates bone loss in osteoporosis, it could be hypothesized that this drug also is effective on cartilage degradation in osteoarthritis (OA). This was investigated in vitro on normal and OA human chondrocytes treated or not treated with interleukin-1beta (IL-1beta). This model mimics, in vitro, the imbalance between chondroformation and chondroresorption processes observed in vivo in OA cartilage. Chondrocytes were isolated from cartilage by enzymatic digestion and cultured for 24-72 h with 10(-4)-10(-3) M strontium ranelate, 10(-3) M calcium ranelate, or 2 x 10(-3) M SrCl2 with or without IL-1beta or insulin-like growth factor I (IGF-I). Stromelysin activity and stromelysin quantitation were assayed by spectrofluorometry and enzyme amplified sensitivity immunoassay (EASIA), respectively. Proteoglycans (PG) were quantified using a radioimmunoassay. Newly synthesized glycosaminoglycans (GAGs) were quantified by labeled sulfate (Na2(35)SO4) incorporation. This method allowed the PG size after exclusion chromatography to be determined. Strontium ranelate, calcium ranelate, and SrCl2 did not modify stromelysin synthesis even in the presence of IL-1beta. Calcium ranelate induced stromelysin activation whereas strontium compounds were ineffective. Strontium ranelate and SrCl2 both strongly stimulated PG production suggesting an ionic effect of strontium independent of the organic moiety. Moreover, 10(-3) M strontium ranelate increased the stimulatory effect of IGF-I (10(-9) M) on PG synthesis but did not reverse the inhibitory effect of IL-1beta. Strontium ranelate strongly stimulates human cartilage matrix formation in vitro by a direct ionic effect without stimulating the chondroresorption processes. This finding provides a preclinical basis for in vivo testing of strontium ranelate in OA. [less ▲]

The use of different dual X-ray absorptiometry brands in a multicenter clinical trial

in Journal of Clinical Densitometry : The Official Journal of the International Society for Clinical Densitometry (1999), 2

Role of the Strontium Ranelate in the prevention of early postmenopausal bone loss : a double-blind, prospective, randomized, placebo-controlled study

in Arthritis and Rheumatism (1998), 41

Regulation of the chondrocyte metabolism by a new divalent strontium salt (S12911)

in BONE (1998), 23(S5), 344

Strontium ranelate as a treatment of vertebral osteoporosis

in Journal of Bone and Mineral Research (1997), 12(S1), 129

IGF-1 but not IL-1bêta effects on the proteoglycan production by chondrocytes are regulated by strontium salts

in Osteoarthritis and Cartilage (1997), 5