A feasibility study aimed at assessing the effect of hormone replacement therapy (HRT) among postmenopausal women with painful hand osteoarthritis (OA) met its predefined progression criteria. The results of the study were published in The Lancet Rheumatology.
Researchers conducted a randomized placebo-controlled double-blind trial (HOPE-e; ClinicalTrials.gov Identifier: NCT04036929) to determine the feasibility and acceptability of a form of HRT (ie, conjugated estrogens plus bazedoxifene) in postmenopausal women with moderate to severe symptoms of hand OA.
It is well recognized that the female sex is an established risk factor for symptomatic OA, particularly hand OA. Hand OA is most common among women in the decade associated with menopause. However, sparse data are available in this regard from large HRT trials.
In the HOPE-e study, the researchers enrolled women aged between 40 and 65 years with definite hand OA in at least 2 painful hand joints and for whom 1 to 10 years had passed after their final menstrual period. Participants were enrolled from 3 primary or secondary care sites, as well as from the community, and were randomly assigned 1:1 for treatment with conjugated estrogens plus bazedoxifene or placebo, administered orally once daily for 24 weeks, then weaned for 4 weeks until the study conclusion.
The primary feasibility outcomes for determining feasibility included enrollment and randomization rates from different enrollment sources; retention rates; study medication compliance (ie, participant-reported adherence, based on daily recording in diaries); and likelihood of unintentional unmasking. Secondary outcomes included patient-reported hand pain during the 14 days prior to each visit, which was measured by 2 methods on a scale of 0 to 10 (0 indicating no pain and 10 indicating the worst pain).
An intention-to-treat analysis was used, with criteria for progression to a full trial predefined as enrollment of at least 30 participants across all sites in 18 months; a dropout rate of 30% or less after randomization; and acceptability. Including rates of adverse events (AEs), to the majority of participants. The enrollment window was reduced to 12 to 15 months because of the COVID-19 pandemic.
Between May 2019 and December 2020, a total of 434 inquiries/referrals were received. Following 96 telephone prescreens and of 35 eligible participants, 7 were excluded from the study. The remaining 28 patients were randomly assigned to the conjugated estrogen/bazedoxifene group (n=14) or the placebo group (n=14). Among the 406 individuals who were not randomly assigned into either group, 250 (62%) were considered ineligible, 101 (25%) did not respond to additional inquiries, and 55 (14%) elected not to proceed with the study (with the most common reason being not wanting to take a hormone-based medication).
All 28 participants completed follow-up evaluations with high compliance and completeness of outcomes measures.
Three AE-related treatment withdrawals were in the placebo group; however, no serious AEs were reported in either group. All participants and investigators were successfully masked (participant Bang’s blinding index placebo group, 0.50; 95% CI, 0.25-0.75). The trial fulfilled the prespecified criteria for progression to a full trial.
Several limitations of the study warrant mention. The number of study participants was at the lower end of the target, thus limiting what could be analyzed from proof-of-concept data; the findings were not generalizable to a larger population; acceptability measures were collected from a small percentage of participants, which most likely led to increased approval rates; and possible biases may have been introduced due to the COVID-19 pandemic,.
The investigators concluded that although powered to detect a clinical effect, the outcome of the study “indicates that a full trial of an HRT in this population is feasible and acceptable and identifies potential refinements with regard to the design of such a trial.”
Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Williams JAE, Chester-Jones M, Lowe CM, et al. Hormone replacement therapy (conjugated oestrogens plus bazedoxifene) for post-menopausal women with symptomatic hand osteoarthritis: primary report from the HOPE-e randomised, placebo-controlled, feasibility study. Lancet Rheumatol. 2022;4(10):e725-e737. doi:10.1016.S2665-9913(22)00218-1