Cell-based therapy injections for the management of knee osteoarthritis: The ESSKA-ICRS consensus. Recommendations using the RAND/UCLA appropriateness method for different clinical scenarios

Purpose: The aim of this consensus was to develop evidence/expert-based patient-focused recommendations on the appropriateness of intra-articular point-of-care (POC) cell-based therapy (CBT) injections in different clinical scenarios of patients with knee osteoarthritis (OA). Methods: The RAND/UCLA Appropriateness Method was used by European experts of the European Society of Sports Traumatology, Knee Surgery and Arthroscopy (ESSKA) and the International Cartilage Regeneration and Joint Preservation Society (ICRS) to reach a consensus and produce recommendations for specific patient categories, combining best available scientific evidence with the collective judgement of a panel of experts. Results: A total of 144 scenarios were developed based on five factors: cell source (bone marrow vs. adipose tissue), age (<50 vs. 50–65 vs. 66–80 vs. >80 years), joint involvement (prevalent tibio-femoral vs. patello-femoral), OA level (Kellgren–Lawrence [KL] Grade 0–I vs. II–III vs. IV) and body mass index (BMI) (<18.5 vs. 18.5–35 vs. >35 kg/m2). Following two voting rounds, agreement was reached for all 144 (100%) scenarios: the indication was considered appropriate in 11.8%, inappropriate in 34.7% and uncertain in 53.5%. The parameters with the highest appropriateness were OA Grade II–III (35.4% appropriate scenarios), age <50 years (22.2% appropriate) and BMI 18.5–35 kg/m2 (20.8% appropriate). The parameters with the highest inappropriateness were age >80 years (88.9% inappropriate), OA grade IV (62.5% inappropriate) and BMI > 35 kg/m2 (50.0% inappropriate). Conclusions: This ESSKA–ICRS expert consensus provides recommendations on the appropriateness of cell-based injectable therapies for knee OA. POC-CBT may be considered, after failure of other non-operative and injectable options, in patients aged ≤65 years with BMI ≤ 35 kg/m2 and KL Grade II–III OA. Unlike bone marrow–derived CBT, adipose-derived CBT was also considered appropriate in patients 66–80 years old with BMI 18.5–35 kg/m2 and KL Grade II–III OA. On the other hand, CBT was considered inappropriate in patients over 80 years old and in those with KL Grade IV OA. These findings may help improve patient selection, although they should not be interpreted as a rigid treatment algorithm but rather as expert-informed guidance for the use of POC-CBT in knee OA. Level of Evidence: Level I.