RESUMO
OBJECTIVE: We here explore whether observed treatment effects of a putative disease-modifying osteoarthritis drug (DMOAD) are greater when cartilage morphometry is performed with rather than without knowledge of magnetic resonance imaging (MRI) acquisition order (unblinded/blinded to time point). METHODS: In the FORWARD (FGF-18 Osteoarthritis Randomized Controlled Trial with Administration of Repeated Doses) randomized controlled trial, 549 knee osteoarthritis patients were randomized 1:1:1:1:1 to three once-weekly intra-articular injections of placebo, 30 µg sprifermin every 6 or 12 months (M), or 100 µg every 6/12 M. After year 2, cartilage segmentation of BL through 24 M MRIs was performed, with blinding to acquisition order. After year 5, 24 and 60 M MRIs were analyzed together, with unknown relative order, but with segmented BL images as reference (24 M unblinded vs. BL), by the same operators. Total femorotibial joint cartilage thickness (TFTJ_ThC) change was obtained for 352 participants analyzed under both conditions. RESULTS: Twenty-four-month data read unblinded to order revealed a -35 ± 44 µm lower TFTJ_ThC than blinded analysis (all groups: lower/upper bounds -120/+51 µm; correlation r2 = 97%). With unblinded analysis, the placebo group lost -46 ± 57 µm TFTJ_ThC over 24 M, whereas 100 µg/every 6 M lost -2.2 ± 73 µm (difference =44 µm [95% CI: 22, 66]). With blinded analysis, placebo lost -11 ± 53 µm, whereas 100 µg/every 6 M gained 30 ± 62 µm (difference = 40 µm [95% CI: 21, 60]). 100 µg sprifermin injected every 6 M showed statistically significant (p < 0.001) treatment effects on TFTJ_ThC, with Cohen D = -0.66 for unblinded and D = -0.69 for blinded analysis. CONCLUSIONS: These results do not reveal that detection of proposed DMOAD treatment is enhanced with MRIs read unblinded to order; rather, the sensitivity is similar to blinded analysis. Choices on blinded vs. unblinded analysis may thus be based on other criteria.