Rheumatologists should not 'ignore' immunogenicity, benefit of background therapies
CHICAGO — Rheumatologists would do well to expand their knowledge about immunogenicity and learn how to mitigate its effects, according to Vibeke Strand, MD, MACR, FACP, a clinical rheumatology professor at the Stanford University School of Medicine and a biopharmaceutical consultant based in Portola Valley, California.
“I know rheumatologists don’t think immunogenicity is very interesting, because we ignore it,” Strand told attendees at the 2019 Interdisciplinary Autoimmune Summit. “And that is fine, because we have lots of therapeutic choices. However, it is worth knowing about, because it explains some of the findings, and so we can use background therapy effectively, because there are cases where background therapy is a good idea.”
According to Strand, the consequences of immunogenicity can range from nothing — or when patients develop antidrug antibodies but nonetheless maintain normal serum levels and achieve good efficacy — to infusion or injection site reactions, to a complete loss of efficacy.
In addition, all TNF inhibitors are associated with certain immunogenicity profiles, Strand said. For example, antidrug antibodies to infliximab (Remicade, Janssen) can result in infusion reactions in rheumatoid arthritis and spondyloarthritis, according to studies. Antidrug antibodies against adalimumab (Humira, AbbVie) can be associated with low or undetectable serum trough drug levels, reduced clinical response and, in rare cases, thromboembolic events.
“Differences in immunogenicity profiles are based on structure, frequency of antidrug antibody formation and observed associations with efficacy,” Strand said. “Patients treated with all TNF inhibitors show variable serum drug levels, in part influenced by immunogenicity but also other factors. For example, intravenous administration and immunogenicity dominate the pharmacokinetics of infliximab.”
According to Strand, background therapy is beneficial for treatment survival and decreases immunogenicity. In particular, patients treated with combination therapy demonstrated a 68% less chance of immunogenicity than those who received monotherapy. If that combination therapy included methotrexate, the patient had a 69% less chance of immunogenicity.
Methotrexate has been observed to reduce the formation of antidrug antibodies, in a dose-dependent manner, in patients with RA, psoriatic arthritis, psoriasis and Crohn’s disease. This effect has been reported with methotrexate combined with infliximab, adalimumab, golimumab (Simponi, Janssen) and certolizumab pegol (Cimzia, UCB), Strand said. However, associations between combination therapy with methotrexate and etanercept (Enbrel, Amgen) in patients with RA have been unclear.
According to Strand, the mechanism by which methotrexate impacts the pharmacokinetics of biologics is not yet clear. However, the effect is evident even in low doses, although higher biologic serum concentrations are associated with better efficacy.
“Standard of care in rheumatology today is based on assessment of disease activity, function and markers of disease progress,” Strand said. “However, I think there is a role for routine assessment of immunogenicity and drug levels in rheumatology that requires further assessment and confirmation.”– by Jason Laday
Strand V. Immunogenicity: Lessons learned in rheumatology. Presented at: Interdisciplinary Autoimmune Summit; April 5-7, 2019; Chicago.
Disclosure: Strand reports consulting fees from AbbVie, Amgen, AstraZenica, BMS, Boehringer Ingelheim, Celltrion, Corrona, Crescendo, Eli Lilly EMD Serono, Genentech/Roche, Glenmark, GSK, Horizon, Inmedix, Janssen, Kypha, Merck, Novartis, Pfizer, Regeneron, Samsung, Sandoz, Sanofi, Selcta, Servier, Setpoint and UCB.