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

Abstract

ObjectiveTo 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).MethodsAn 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.ResultsADAb 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.ConclusionThe optimization of biologic therapies by taking into proper account the above issues would improve patient outcomes.

Mechanisms underlying DMARD inefficacy in difficult-to-treat rheumatoid arthritis: a narrative review with systematic literature search

“…The formation of ADAs can lead to neutralization of bDMARDs and subtherapeutic serum drug levels (i.e. immunogenicity) [ 4 , 80 , 86 , 94 , 101 , 103 , 121 ]. ADAs are mainly IgM and IgG antibodies although IgE antibodies may also occur [ 23 , 86 ].…”

Impact of immunogenicity on clinical efficacy and toxicity profile of biologic agents used for treatment of inflammatory arthritis in children compared to adults

“… 28 Non-neutralising ADAs decreased the circulating levels of abatacept by enhancing drug clearance in adults. 44 , 51 In children, ADAs were also found to be non-neutralising but were not found to be associated with low abatacept concentrations. 62 , 97 …”

“…The prevalence of ADAs to fusion proteins, such as abatacept (which comprises an Fc region of IgG1 fused to the extracellular domain of CTLA-4) is generally acknowledged to be lower than to therapeutic mAbs. The prevalence of ADAs to abatacept ranged from 1% to 20% in adult studies, 28 , 44 , 51 , 65 and from 8.7% to 23.3% in paediatric studies 35 ( Table 2 ). Younger children with JIA (2–5 years) had a higher prevalence of ADAs than older children (6–17 years).…”

“…The prevalence of ADAs against adalimumab has high variability across different types of autoimmune diseases in adults 25 , 28 , 31 , 50 – 52 and children with JIA 35 ( Table 1 ). The timing of adalimumab ADA development is controversial: in some adult studies ADA prevalence did not increase with treatment duration, 53 , 54 while in other studies there was a significant increase, with ADA developing between 4.5 months and 12 months of treatment.…”

Exposure–Response Relationship of Certolizumab Pegol and Achievement of Low Disease Activity and Remission in Patients With Rheumatoid Arthritis

“…1,3,[7][8][9][10][11][12][13][14][15] Poor compliance to therapy (particularly for subcutaneously administered anti-TNFs, which can be self-injected by patients) and the development of antidrug antibodies (ADAb) are possible explanations for subtherapeutic plasma or serum drug concentrations. 16 Neutralizing ADAb may reduce the efficacy of anti-TNFs by blocking the cytokine-binding site, 17,18 preventing drug absorption from the injection site, 19 and/or by accelerating drug clearance. 15,[20][21][22] Varying rates of immunogenicity have been reported for anti-TNFs, depending on the drug and assay used.…”