Antihistamines potentially beneficial for knee OA

The use of antihistamines was associated with reduced structural progression in knee osteoarthritis (OA), according to a post hoc analysis of two large phase III trials.

Mast cells are prevalent in the synovial tissues of patients with OA. Evidence shows that mast cells are involved in chronic inflammation, and that their activity in the synovium may contribute to structural progression of OA. [Osteoarthritis Cartilage 2016;24:664-671] “Mast cell numbers and degranulation status have been shown to correlate with synovitis and cartilage damage in OA patients,” said Asger Bihlet from Nordic Bioscience Clinical Development A/S and Sanos Group, Herlev, Denmark, at EULAR 2022. “However, the exact role of mast cells in OA remains unclear.”

“As one of the primary effects of antihistamines is mast cell degranulation, we hypothesized that for people with OA, the use of antihistamines is associated with a reduced risk of structural progression,” said Bihlet.

Bihlet and colleagues analysed data from 2,206 patients participating in studies evaluating oral salmon calcitonin vs placebo. Of these, 1,485 (mean age 64 years, 69 percent female) who had baseline and year 2 radiographs were categorized into two groups: no antihistamine use vs any antihistamine use (n=1,327 vs 158). Antihistamine use was stratified into short- mid-, long-term use (1–49 days, 50–299 days, and >300 days, respectively). [EULAR 2022, abstract OP0230]

After adjusting for age, sex, BMI, and baseline joint space width (JSW), those reporting any antihistamine use had a decreased change in JSW as opposed to those who reported no antihistamine use (mean change, –0.19 vs –0.32 mm; p=0.02).

When stratifying by duration of antihistamine use, there was an inverse duration-dependent association between antihistamine use and JSW narrowing over time (p_trend=002). “[This finding implies] that the longer the use of antihistamine, the lower the structural progression over time,” explained Bihlet.

The findings support evidence demonstrating an association between H₁-antihistamine use and reduced OA prevalence. [Arthritis Res Ther 2018;20:116] However, the probable differences between antihistamine doses and types were not evaluated in the study. “[Also,] analysis of changes in symptoms was not performed, so clinical relevance is uncertain,” said Bihlet.

“[Nonetheless, findings from this post hoc analysis suggest that] participants taking antihistamines underwent less structural progression compared with those who did not take antihistamines during the 2-year study period,” he said. “The observed reduction in structural progression appears to be associated with the duration of antihistamine treatment.”

Given the post hoc nature of the study, randomized trials are warranted to further elucidate the role of specific antihistamines in OA.