ObjectiveWe 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 MRI acquisition order (unblinded/blinded to time point). MethodsIn the FORWARD randomized controlled trial, 549 knee osteoarthritis patients were randomized 1:1:1:1:1 to three once-weekly intra-articular injections of placebo, 30µg sprifermin every 6 or 12 months(M), or 100µg every 6/12M. After year 2, cartilage segmentation of baseline through 24M MRIs was performed, with blinding to acquisition order. After year 5, 24 and 60M MRIs were analyzed together, with unknown relative order, but with segmented BL images as reference (24M unblinded vs. BL), by the same operators. Total femorotibial joint cartilage thickness (TFTJ_ThC) change was obtained for 352 participants analyzed under both conditions. Results24M data read unblinded to order revealed a -35±44 µm lower TFTJ_ThC than blinded analysis (all groups: lower/upper bounds -120/+51µm; correlation r2=97%). With unblinded analysis, the placebo group lost -46±57µm TFTJ_ThC over 24M, whereas 100µg/every 6M lost -2.2±73µm (difference=44µm [95%CI: 22,66]). With blinded analysis, placebo lost -11±53µm, whereas 100µg/every 6M gained 30±62µm (difference=40µm [95%CI: 21,60]). 100µg sprifermin injected every 6M showed statistically significant (p<0.001) treatment effects in TFTJ_ThC, with Cohen D=-0.66 for unblinded and D=-0.69 for blinded analysis. ConclusionsThese 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.