TNF Inhibitor Response in Women vs Men With Ankylosing Spondylitis

Needle in vile
Needle in vile
Investigators evaluated sex differences in the effectiveness of tumor necrosis factor inhibitors in patients with ankylosing spondylitis.

Women with ankylosing spondylitis (AS) demonstrated poorer response to tumor necrosis factor inhibitor (TNFi) therapy than men, confirming prior observations by rheumatologists treating this population, according to a study published in The Journal of Rheumatology.

For years, AS was thought to predominantly affect men, but clinicians have recently also recognized the presence of AS in a substantial percentage of women. However, there are often distinct phenotypic differences in the presentation and clinical appreciation between the sexes. Women typically experience shorter illness duration but increased delay in diagnosis compared with men. The investigators sought to explore whether these sex differences extended to TNFi response, as has been previously reported.

The researchers recruited 440 patients with AS (66.8% men) for a longitudinal analysis between January 2005 and April 2016, based on data from the Swiss Clinical Quality Management cohort. All individuals were undergoing initial TNFi therapy at the time. The primary outcome was 20% improvement in the Assessment of Spondyloarthritis international Society criteria (ASAS20). Additional efficacy outcomes included 40% improvement (ASAS40) and inactive disease according to the Ankylosing Spondylitis Disease Activity Score (ASDAS <1.3).

At baseline, women exhibited more peripheral disease and greater spinal mobility, with lower body mass index and C-reactive protein measurements and fewer positive human leukocyte antigen (HLA)-B27 serologies. Women were also less likely to be smokers. Otherwise, indices of disease activity (Bath Ankylosing Spondylitis Disease Activity and ASDAS scores) and quality of life were similar in both sexes.

At the 1-year follow-up, 52% of women and 63% of men achieved an ASAS20 response (odds ratio [OR], 0.63; 95% CI, 0.37-1.07; P =.09). With regard to inactive disease, ASDAS <1.3 was observed in 18% of women and 26% of men (OR, 0.65; 95% CI 0.32-1.27; P =.22).

After adjustment for various predictors, the response analysis revealed a more pronounced and statistically significant difference between the sexes. ASAS20 response had an adjusted OR of 0.34 (95% CI, 0.16-0.71; P =.005), while ASDAS <1.3 saw an adjusted OR of 0.10 (95% CI 0.03-0.31, P <.001). Analyses of other secondary outcomes confirmed the apparent sex differences for TNFi response after 1 year, with ASAS40 demonstrating an adjusted OR of 0.44 (95% CI, 0.21-0.91; P =.03).

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Strengths of the study included the prospective design, standardized measurements using validated tools that permitted assessment of multiple response variables, and the use of central scoring for pelvic imaging to confirm AS.

The investigators also noted several study limitations, including lack the collection of MRI scans for all patients, which impaired analysis of possible symptom/inflammation uncoupling in women; availability of only 77% of initial participants for follow-up; lower number of patients suitable for adjusted analysis; and the potential for comorbidities being under-reported, leading to possible residual confounding factors.

The results confirmed that after adjusted analysis, women with AS experience lower efficacy in response to TNFi therapy than men, despite similar disease burdens at baseline.

There were no disclosures or conflicts of interest declared.

Please see original article for funding information.

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Hebeisen M, Neuenschwander R, Scherer A, et al. Response to tumor necrosis factor inhibition in male and female patients with ankylosing spondylitis: data from a Swiss cohort [published online February 15, 2018]. J Rheumatol. doi:10.3899/jrheum.170166