Immunogenicity to biological drugs in psoriasis and psoriatic arthritis

Abstract

Monoclonal antibodies or fusion proteins, defined as biological drugs, have modified the natural history of numerous immune-mediated disorders, allowing the development of therapies aimed at blocking the pathophysiological pathways of the disease, providing greater efficacy and safety than conventional treatment strategies. Virtually all therapeutic proteins elicit an immune response, producing anti-drug antibodies (ADAs) against hypervariable regions of immunoglobulins. Immunogenicity against biological drugs can alter their pharmacokinetic and pharmacodynamic properties, thereby reducing the efficacy of these drugs. In more severe cases, ADAs can neutralize the therapeutic effects of the drug or cause serious adverse effects, mainly hypersensitivity reactions. The prevalence of ADAs varies widely depending on the type of test used, occurrence of false-negative results, and non-specific binding to the drug, making it difficult to accurately assess their clinical impact. Concomitant use of immunosuppressors efficiently reduces the immunogenicity in a dosedependent manner, either by decreasing the frequency of detectable ADAs or by delaying their appearance, thereby enhancing the effectiveness of biological therapies. Among the new therapeutic strategies for the management of psoriasis, biological agents have gained increasing importance in recent years as they interrupt key inflammation pathways involved in the physiopathology of the disease. Reports regarding ADA in new biologics are still scarce, but the most recent evidence tends to show little impact on the clinical response to the drug, even with prolonged treatment. It is therefore essential to standardize laboratory tests to determine the presence and titles of ADAs to establish their administration and management guidelines that allow the determination of the real clinical impact of these drugs.

Psoriatic arthritis: the role of self-reported non-adherence, non-trough drug levels, immunogenicity and conventional synthetic DMARD co-therapy in adalimumab and etanercept response

“…The frequency of ADAb development in PsA patients treated with ADL is in keeping with previous publications [ 14–17 , 35 ]. However, previous studies draw conflicting conclusions about the effect of csDMARD co-therapy on ADAb production in such patients [ 14 , 15 , 39 ]. A previous smaller study reported a lack of association, highlighting the strength of the larger cohort size in this study [ 14 ].…”

“…A previous smaller study reported a lack of association, highlighting the strength of the larger cohort size in this study [ 14 ]. Conversely, two larger studies, one of which focused on patients with psoriasis, found that concomitant use of immunosuppressors, including MTX, was associated with a reduction in detectable ADAb [ 15 , 39 ]. However, those studies did not investigate whether different csDMARDs had differing effects.…”

“…In PsA, ADAb to the monoclonal antibody ADL have been reported in between 6 and 45% of patients, with ≤97.7% of ADL ADAb being neutralizing [ 14–17 ]. Increased ADAb levels are not only associated with decreased treatment response, but also with increased risk of adverse reactions, such as hypersensitivity [ 15 ]. In RA, csDMARD co-therapy is associated with a significant reduction in the prevalence of ADAb [ 18 ].…”

“…In RA, csDMARD co-therapy is associated with a significant reduction in the prevalence of ADAb [ 18 ]. The concomitant prescription of TNF-i and csDMARD therapies is common practice in PsA; however, the effect of co-prescription has not been explored fully [ 14 , 15 ]. Understanding factors affecting the development of ADAb in PsA could optimize TNF-i drug levels and improve drug response.…”

Review of Tralokinumab in the Treatment of Atopic Dermatitis

“…In addition, there is always potential for immunogenicity for all therapeutic proteins. 33 Although most patients who receive treatment with dupilumab do not develop antibodies against the drug, immunogenicity against a biologic reduces its efficacy and causes treatment-resistant disease. 33 Tralokinumab offers an efficacious alternative in such cases.…”