Biologic medications, such as TNF inhibitors (TNFi) and IL-17 inhibitors (IL-17i), are the current standard in rheumatologic treatment of moderate to severe spondyloarthritis. But what happens when patients don’t respond to this class of medications?
A French study followed axial spondyloarthritis (axSpa) patients as they were given their first TNFi medication. Of the 222 patients in the study, 27 (12 percent) did not respond to their first TNFi. (This is called “primary TNFi inefficacy.”) This statistic corresponds with the five to 15 percent primary TNFi inefficacy rate in axSpa patients reported in earlier studies.
The investigators were able to conduct follow ups with 25 of the 27 axSpa patients who had failed their primary TNFi. Follow ups were conducted after a period of five to 10 years (mean time of six years).
Study Findings
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- 72 percent (18) of the 25 patients with primary TNFi inefficacy had one or more of the following comorbidities (conditions in addition to spondyloarthritis) contributing to their symptoms: widespread pain syndrome, osteoarthritis, depression.
- “Five patients — all females — had widespread pain syndrome according to the Fibromyalgia Rapid Screening Tool questionnaire. Another 10 patients had osteoarthritis of lower-limb peripheral joints or of the spine, while an additional 8 had self-declared depression, for which 3 were taking antidepressants.”
- 50 percent (nine) had success with the second TNFi tried and were still on their second TNFi a year after having starting it.
- At follow up (at five to 10 years), nine people had received two TNFi drugs, and seven had received three or more.
- In total 50 percent (nine) were still prescribed a TNFi at the time of follow up.
Study’s Main Clinical Point
A second TNFi may be useful in axSpA patients with primary inefficacy to their first TNFi, but [the physician should] also consider the impact of painful comorbidities.
Other Points
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- A lack of response to the first TNFi tried for spondyloarthritis (primary TNFi inefficacy) should not be cause to question the diagnosis of spondyloarthritis.
- The fact that most of the patients with primary inefficacy to their first TNFi had confirmed axSpA but also had comorbidities that could affect axSpA evaluation ‘is important because practitioners might consider that primary inefficacy to TNFi leads to reconsidering the diagnosis of SpA (i.e. the notion of a TNFi prescription being used as the diagnostic test). We suggest here that primary inefficacy should not be considered as equivalent to a diagnostic error, and that a second prescription of TNFi may be of use in such patients, although painful comorbidities should certainly be screened for and taken into account.’
- Women, older patients at time of first TNFi use, those with higher functional impairment scores, and those without clearly elevated blood inflammation levels were more prone to find their first TNFi ineffective.
