medwireNews: Findings from two studies suggest that sprifermin has a broadly beneficial impact on joint structure in people with knee osteoarthritis (KOA), but symptomatic efficacy may be restricted to specific patient populations.
In the first study, Guo-Xin Ni and colleagues from The First Affiliated Hospital of Fujian Medical University in Fuzhou, China, conducted a meta-analysis of eight randomized placebo-controlled trials evaluating intra-articular sprifermin injections in KOA patients with a follow-up duration of 6 months–3 years.
They found “strong evidence” to support a beneficial effect of sprifermin, also known as recombinant human fibroblast growth factor 18, on joint structure. Participants treated with the drug gained more and lost less cartilage thickness in the total femorotibial joint (TFTJ) than those given placebo, with a significant standardized mean difference (SMD) of 0.55 mm. Sprifermin-treated patients also experienced significantly greater increases in cartilage volume in the total knee region (SMD=0.39 mm).
Ni et al report, however, that the impact of sprifermin on KOA symptoms “seems to be inconclusive.” In the two trials investigating symptom efficacy, participants treated with sprifermin experienced a significantly smaller improvement in WOMAC total, pain, function, and stiffness scores than those given placebo.
While these findings suggest “it is unlikely that intra-articular sprifermin leads to significant improvement in physical function and clinical symptoms,” efficacy may “change with time and in relation to patient baseline characteristics,” write the researchers in Arthritis Research & Therapy. They recommend that “[f]urther investigations are required to understand its long-term effect on clinical symptoms and functions in a targeted population.”
The second study – a post-hoc analysis of the FORWARD trial – aimed to shed more light on the efficacy of sprifermin in a specific subpopulation of KOA patients with high risk for progression.
Philip Conaghan (University of Leeds, UK) and co-investigators’ analysis focused on 161 of the 549 FORWARD participants who had a baseline medial or lateral minimum joint space width of 1.5–3.5 mm and a WOMAC pain score of 40–90 points.
In this subgroup, WOMAC pain scores at the 3-year follow-up were significantly lower among those treated with sprifermin 100 µg every 6 months versus placebo, with an adjusted mean between-group difference of 8.75 points. This difference was not seen in the overall intent-to-treat (ITT) population, with a nonsignificant adjusted mean between-group difference of 0.97 points.
Conversely, net TFTJ cartilage thickness gain among sprifermin- versus placebo-treated patients was comparable in the high-risk subgroup and the overall ITT population, with adjusted mean differences of 0.06 and 0.05 mm at 2 years, respectively.
“This is the first analysis to provide a proof of concept that structure (cartilage thickness) modification in knee OA by an [intra-articular] drug may translate into symptomatic clinical benefit, provided an adequate patient cohort with established disease is selected and followed for a duration long enough to determine potential symptom benefits,” write the researchers in Seminars in Arthritis and Rheumatism.
Noting that “[b]oth structural and symptomatic benefit are needed for an agent to be considered a DMOAD [disease-modifying OA drug],” the investigators conclude that the high-risk patient subgroup identified in their analysis could “represent a target population for future clinical trials of sprifermin or other potential DMOADs.”
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Arthritis Res Ther 2021; 23: 107
Semin Arthritis Rheum 2021; 51: 450–456