Patients Who Don’t Respond Initially to TNFi inhibitors Share Similarities, Study Finds

Janet Stewart, MSc avatar

by Janet Stewart, MSc |

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Axial spondyloarthritis patients who do not respond initially to treatment with TNF-alpha inhibitors (TNFi) share some commonalities, researchers discovered in a study aimed at evaluating factors associated with TNFi failure.

In particular, researchers found these patients tend to be older, lack a protein marker associated with the disease, have higher rates of disease activity before beginning treatment, and often are treated with a specific kind of TNFi — a soluble TNFR.

The article, titled “Profiling Response to TNF-Inhibitor Treatment in Axial Spondyloarthritis,” was published in the journal Arthritis Care & Research.

Up to 50 percent of patients with axial spondyloarthritis who take TNF inhibitors switch to an alternative biologic. Researchers set out to find out how many cases are due to a lack of response to this type of medication. They evaluated how many patients did not initially respond to TNFi, called primary lack of response (PLR), experienced a loss of effectiveness after an initial good response, called secondary lack of response (SLR), or responded well to the treatment, termed responders.

The study included 249 axial spondyloarthritis patients who were taking TNF inhibitors for the first time. Records in the database at the adult Spondylitis Clinic at the Toronto Western Hospital from patients seen between July 2003 and December 2016 were analyzed.

Patients’ ages,  levels of disease activity measured using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) before beginning treatment, and the type of TNF-alpha inhibitor used, were all included in the analysis. HLA-B27 status — a variant of a protein found on some immune system cells — also was taken into account. Its presence is associated with ankylosing spondylitis and other autoimmune disorders. However, not all ankylosing spondylitis patients are HLA-B27 positive.

Males accounted for 70.7 percent of the study subjects, who were an average of 37.3 years old, plus or minus 12.4 years. Lack of initial response (PLR) was seen in 62 patients, loss of effectiveness (SLR) in 93, and 94 patients responded to treatment.

The breakdown of patients receiving the TNF inhibitors Remicade (infliximab), Enbrel (etanercept), Humira (adalimumabe) and Simponi (golimumab) was 33.3%, 25.3%, 28.1% and 13.3%, respectively. Of the 249 patients, 63 were treated with medication consisting of soluble TNF-alpha receptors and 186 with monoclonal antibodies against TNF-alpha.

Nearly 40 percent of all TNFi failures were due to a lack of initial response. These patients tended to be older, be HLA-B27 negative, have higher disease activity levels at the beginning of treatment, and were treated with soluble TNFR.

Using statistical analysis to interpret the results, these four factors were the independent predictors of a primary lack of response.

“In conclusion, lack of efficacy is an important aspect of TNFi treatment with considerable clinical and cost implications. Nearly 40% of the lack of efficacy patients can be classified as PLR and AxSpA patients with this type of failure may have distinct features such as increased age, negative HLA-B27 and higher baseline BASDAI,” the researchers wrote.