A Practical Approach to the Use of Conventional Synthetic, Biologic and Targeted Synthetic Disease Modifying Anti-Rheumatic Drugs for the Treatment of Inflammatory Arthritis in Patients with a History of Malignancy.

PURPOSE OF REVIEW: Conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) have been used in the treatment of inflammatory arthritis (IA) for many years. More recently, biologic (bDMARDs) and targeted synthetic (tsDMARDs) DMARDs have further improved treatment. Due to increased patient longevity and effective oncology treatment, rheumatologists often encounter patients with IA and previous malignancy. The immunosuppressive effect of DMARDs causes concern regarding impaired tumour surveillance with a potential increased risk of malignancy. We reviewed the literature regarding the risk of malignancy in patients on cs-/b-/tsDMARDS and sought to provide practical advice regarding use of these drugs in patients with previous malignancy. RECENT FINDINGS: Data from randomised controlled trials is limited as patients with pre-existing malignancy are often excluded. Reassuringly, an increasing range of "real world" data from various national b/tsDMARD registries has not provided a convincing signal that these drugs increase tumour recurrence. Nevertheless, awareness of, and adherence to, national screening guidelines for malignancy is important. Given the improvement in quality of life achieved with these novel and well-tolerated therapeutic agents, the benefit/risk profile remains overwhelmingly favourable in most patients.

Substituted azaquinazolinones as modulators of GHSr-1a for the treatment of type II diabetes and obesity.

Substituted azaquinazolinones were identified as antagonists of the GHSr-1A receptor for the treatment of type II diabetes and obesity. Optimisation for potency and LogD lead to the identification of orally bioavailable, potent antagonists with improved selectivity over hERG.