Rheumatologists prescribe tumor necrosis factor inhibitors (TNFi’s) to manage axial spondyloarthritis (axSpA) for some patients. In addition to their anti-inflammatory effects, TNFi’s have a wide range of direct effects on bone turnover, some of which may benefit axSpA patients. Example: A study in mice that overexpress TNF on the cell surface suggests that TNF may play a role in the ankylosis that occurs in patients with axSpA.1
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A 2021 study suggests that, for patients with axSpA, TNFi’s may reduce spinal disease progression, as measured by the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS)—a radiographic, but not clinical, measure of disease progression. The findings by Alexandre Sepriano, MD, PhD, a rheumatologist at Egas Moniz Hospital, Lisbon, Portugal, and a researcher at the Leiden University Medical Center, the Netherlands, and colleagues from the University of Alberta, Canada, indicate TNFi’s may affect progression, as measured by the Ankylosing Spondylitis Disease Activity Score (ASDAS), a clinical measure of disease activity. TNFi’s may also have a direct effect on the progression of disease in the spine that is not captured by the ASDAS. The study results were published in the July issue of Arthritis & Rheumatology.2
The cross-Atlantic collaboration recruited 314 patients with axSpA from both academic and community-based practices in northern Alberta, Canada, and followed the patients in clinical practice. The investigators evaluated treatment with a TNFi at each visit (yes/no; time-varying). They also analyzed treatment with TNFi according to the following definitions: treatment with TNFi at any time during the follow-up interval (yes/no; time-varying), duration of treatment with any TNFi during the follow-up interval (yes/no; time varying), proportion of time receiving TNFi treatment during the follow-up interval (continuous variable as a proportion of follow-up; time varying), duration of TNFi treatment <50% vs. or greater of the follow-up interval (yes/no; time-varying), and duration of continuous TNFi treatment (allowing for interruptions of a maximum of six months) ≤4 years vs. >4 years (yes/no; time-fixed).
“What we found,” says Dr. Sepriano, “is that there’s an effect of these drugs on the progression of disease in the spine.”
This observational study documented a reduction in clinical symptoms as measured by the ASDAS in patients treated with TNFi. The investigators were surprised to find the symptom reduction as measured by the ASDAS did not fully explain the beneficial effect of TNFi’s on structural progression. Thus, the researchers hypothesized TNFi’s affected progression indirectly by suppression of inflammation, as measured by the ASDAS, and directly, by inhibiting radiographic mSASSS progression. The authors propose that it does this through direct biologic actions on the bone. Example: TNFi may be acting on granulation tissue in the subchondral bone marrow.3 The cells that line the granulation tissue express typical markers of osteoblasts and osteoclasts. The invasion of the granulation tissue into the subchondral bone and the colocalization of aberrant bone formation with this tissue are consistent with the hypothesis that that this granulation tissue plays an important role in the progressive joint remodeling and ankylosis in radiographic axial SpA and may respond directly to TNFi.4 This direct effect does not appear to be captured by the ASDAS. In a caveat, the authors acknowledge this direct effect of TNFi’s on mSASSS scores may still be an effect of TNFi’s on inflammation not captured by the ASDAS.