Safety, Tolerability, and Efficacy of Hox Alpha, a Dry Extract from Stinging Nettle Leaves versus OTC NSAIDs in Osteoarthritis: A Retrospective, Propensity-Matched 12-Week Analysis from the German Pain e-Registry (SIPHARO Study)

J Pain Res. 2026 Feb 19;19:546747. doi: 10.2147/JPR.S546747. eCollection 2026.

ABSTRACT

BACKGROUND: Pharmacological self-management of osteoarthritis (OA) with over the counter (OTC) drugs remains challenging.

AIM: To compare the safety, tolerability, and efficacy of a finished phytotherapeutic product (FPP; 2-propanolic dry extract from stinging nettle leaves, Hox alpha [HOXA]) with conventional non-steroidal anti-inflammatory drugs (NSAIDs) used as OTC self-medication in OA.

METHODS: Retrospective, longitudinal exploratory analysis of depersonalized data from the German Pain e-Registry. Two propensity score-matched cohorts of 1073 OA patients each, reporting at least 3 months of continuous OTC treatment with HOXA or NSAIDs, were evaluated. The composite primary endpoint was the proportion of patients who did not discontinue due to an adverse drug reaction (ADR) AND achieved a clinically relevant reduction in average 24‑h pain intensity at the end of the evaluation period. Secondary endpoints included improvements in pain intensities, pain‑related disability, and physical/mental quality of life; safety analyses assessed ADR frequency, number of affected patients, and ADR‑related discontinuations.

RESULTS: Both treatments were associated with significant relief of OA-related symptoms compared to baseline, with greater improvements observed for HOXA across all evaluated domains (all p < 0.001). The frequency of ADRs (789 vs 152), the proportion of patients with ADRs (46.8 vs 13.1%) and ADR-related discontinuations (25.2 vs 2.1) were all significantly higher with NSAIDs compared to HOXA (all p < 0.001). The composite primary endpoint was achieved by 96.2% (HOXA) vs 73.2% (NSAIDs; p < 0.001; OR 9.23; RR 7.02; effect size 0.319).

CONCLUSION: In this real‑world OTC setting, HOXA use was associated with fewer ADRs and more favorable multidimensional outcomes compared with NSAID. Given the retrospective design, these findings should be interpreted as exploratory and hypothesis‑generating and confirmed in randomized controlled trials.

TRIAL REGISTRATION: HMA‑EMA Catalogues of real‑world data sources and studies; EU PAS number 1000000564 (encepp.europa.eu).

PMID:41737297 | PMC:PMC12927808 | DOI:10.2147/JPR.S546747