Personalization of biologic therapy in patients with rheumatoid arthritis: less frequently accounted choice-driving variables

Laura Niccoli,1 Carlotta Nannini,1 Corrado Blandizzi,2 Stefania Mantarro,2 Marta Mosca,3 Ombretta Di Munno,3 Delia Goletti,4 Maurizio Benucci,5 Francesca Li Gobbi,5 Emanuele Cassarà,1 Olga Kaloudi,1 Fabrizio Cantini1 1Department of Rheumatology, Hospital of Prato, Prato, Italy; 2Section of Pharmacology and Pharmacovigilance, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; 3Division of Rheumatology, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; 4Translational Research Unit, Department of Epidemiology and Preclinical Research, National Institute for Infectious Diseases, Rome, Italy; 5Rheumatology Unit, Hospital S. Giovanni di Dio, Florence, Italy Objective: To propose appropriate statements that drive the choice of biologic therapies in patients with rheumatoid arthritis (RA), factoring in their impact on the following issues: anti-drug antibody (ADAb) formation, suspicion and management of infections, lupus-like syndrome (LLS), effects on bone mass and sexual sphere, and relationship between RA and periodontal disease (PD). Methods: An overview of existing evidence was undertaken by an expert panel on behalf of the Italian board for the TAilored BIOlogic therapy (ITABIO). Data were extracted from controlled trials, national registries, national health care databases, post-marketing surveys, and, when required by the paucity of controlled studies, from open-label clinical series. Anti-tumor necrosis factor (anti-TNF) and non-anti-TNF-targeted biologics approved for RA were investigated. Results: ADAb formation is chiefly associated with anti-TNFs, and it is reduced by combination therapy with methotrexate. To date, ADAb titration is not advisable for clinical practice, and, in case of anti-TNF secondary failure, a non-anti-TNF biologic is indicated. LLS is observed in anti-TNF receivers and, in most cases, resolves without anti-TNF withdrawal. A non-anti-TNF biologic is advisable in patients experiencing LLS. Non-anti-TNFs demonstrated a low or absent infection risk and are preferable in patients with comorbidities. Due to their positive effects on bone mass, anti-TNFs are indicated in women at osteoporosis risk, whereas non-anti-TNF have been poorly investigated. The emerging evidence of the relationship between RA and PD and the effects on anti-TNF efficacy should lead clinicians to consider the periodontal status in RA patients. Anti-TNFs may exert a positive effect on fertility and sexuality, and clinicians should explore these aspects in RA patients. Conclusion: The optimization of biologic therapies by taking into proper account the above issues would improve patient outcomes. Keywords: biologics, immunogenicity, infections, lupus-like syndrome, osteoporosis, periodontal disease, sexualit

Circulating levels of Nε-(carboxymethyl)lysine are increased in systemic sclerosis

Objective. Advanced glycation endproducts (AGEs), including N ε-(carboxymethyl)lysine-protein adducts (CML) are involved in micro/ macrovascular changes and are co-localized with adhesion molecules in inflamed tissues. Serum levels of CML were investigated in systemic sclerosis (SSc) characterized by microvascular modifications and correlated with indices of micro/macrovascular damage. Methods. In 66 SSc patients (limited SSc, n = 55; diffuse SSc, n = 11) and 20 controls, CML serum levels were measured by enzyme-linked immunosorbent assay. Nailfold capillaroscopy, intima-media thickness (IMT) and the ankle-brachial index (ABI) were also recorded, to characterize micro/macrovascular involvement. Results. CML levels were significantly higher in SSc (79.2 ± 39 mg/ml vs 49.6 ± 26.1 mg/ml, mean ± s.d.; P <0.01), without significant differences between SSc subsets. CML levels were significantly higher in all capillaroscopic patterns: the 'early' pattern showed higher levels than 'active' and 'late' patterns. IMT was significantly higher in SSc (P <0.01) than in controls, whilst ABI was no different from controls. Conclusions. These data indicate that although both CML formation and macrovascular involvement are increased in SSc, there is no correlation between these two parameters. However, the characteristic early nailfold capillaroscopy changes of SSc are associated with proportionally greater CML formation, suggesting that AGEs are involved in SSc microangiopathy