Osteoarthritis - Emerging treatments

Extracorporeal shockwave therapy (ESWT)

Extracorporeal shockwave therapy has been demonstrated to reduce pain and improve functionality in patients with OA of the knee at up to 12 months, with only minor adverse effects.[224][225][226] However, there remains a lack of clarity regarding the frequency and dose levels of ESWT required to achieve the maximum improvement.[226] Further long-term trials are needed.

Autologous conditioned serum (ACS)

Randomised controlled trials and observational studies suggest that autologous conditioned serum may be of some benefit with respect to pain control and functional recovery in patients with OA, but a disease-modifying effect has not been convincingly demonstrated.[227][228][229][230]

Platelet-rich plasma (PRP) intra-articular injections

Meta-analyses suggest that PRP intra-articular injections may provide symptomatic relief in OA.[231][232][233][234][235][236][237] The UK National Institute for Health and Care Excellence reports that evidence on PRP injections for knee OA is limited in quality, and therefore, this procedure should only be used with special arrangements for clinical governance, consent, and audit or research.[238] The American College of Rheumatology (ACR) does not recommend PRP intra-articular injections for patients with knee or hip OA.[7] Meta-analyses comparing PRP with hyaluronic acid and other injectable options in patients with OA of the knee suggest that PRP is either more beneficial than hyaluronic acid and other injectables, or patients can expect a similar beneficial short-term outcomes with PRP compared with hyaluronic acid.[239][240][241][242] The benefits of PRP for the treatment of knee OA may increase over time, becoming clinically significant after 6-12 months.[242] However, the improvement remains partial and is supported by low-level evidence. Further research is needed to confirm the benefits of PRP and identify the best formulation and indications for PRP injections in knee OA.[239][242] Evidence on the effectiveness of PRP to treat OA of the ankle varies. One meta-analysis demonstrated an improvement of pain and function for patients with OA of the ankle in the short term (12 weeks), while a second meta-analysis reported no improvement of symptoms or function for PRP at 52 weeks compared with placebo.[237][243]

Radiofrequency ablation

Radiofrequency ablation, a minimally invasive treatment option, employs a high temperature probe to target nervous tissue of interest. Meta-analyses report significant improvement in pain for up to 12 months when used to treat knee OA.[244][245][246][247][248][249][250] Concerns exist regarding procedural protocols, study sample size and quality, and patient follow-up; further, high-quality studies are warranted.[248] Genicular nerve thermal radiofrequency ablation has been demonstrated to be more effective compared with non-steroidal anti-inflammatory drugs and intra-articular corticosteroid injections at reducing pain, improving function and quality of life in patients with OA of the knee.[251] Two subsequent meta-analyses found that genicular artery embolisation is an effective treatment for reducing pain for patients with mild, moderate, or severe knee OA refractory to conservative management, without any serious complications.[252][253]

Tapentadol

Tapentadol is a centrally acting analgesic mu-opioid receptor agonist and norepinephrine (noradrenaline) reuptake inhibitor. Pooled analysis of two double-blind, randomised, placebo- and oxycodone (controlled release)-controlled studies found that prolonged-release tapentadol provided significantly more effective pain relief than oxycodone (controlled release) in patients with moderate-to-severe chronic OA knee pain.[254] Tapentadol appears to be associated with reduced risk for vomiting, constipation, nausea, somnolence, and pruritus compared with oxycodone.[254] [ ]

Ketorolac

Randomised controlled trials suggest that intra-articular ketorolac injection provides comparable improvement in patient-reported outcome measures to intra-articular corticosteroid in patients with knee or hip OA.[255][256] In one trial, pain remained significantly decreased from baseline at 24 weeks in both treatment arms.[256]

Cell-mediated gene therapy

Phase 2 and phase 3 studies of cell-mediated gene therapy in patients with knee OA report statistically significant improvements in function and pain.[257][258] Larger, multicentre trials are required.

Stem cell therapy

Meta-analyses suggest that intra-articular mesenchymal stem cell therapy reduces pain in patients with OA of the knee, but that evidence of disease-modifying effects (e.g., cartilage repair) remains limited.[259][260][261][262][263][264][265] The ACR does not recommend stem cell injections for patients with knee or hip OA.[7]

Combined intra-articular injections

One systematic review reported that combined intra-articular injections of a corticosteroid and hyaluronic acid reduced WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) pain scores at 2 to 4 weeks, 24 to 26 weeks, and 52 weeks, compared with hyaluronic acid injections alone in patients with OA of the knee.[266] A comparison of combined intra-articular injections of PRP and hyaluronic acid reported that the combined intra-articular injection improved patient-reported outcomes compared with hyaluronic acid alone, but it was not more effective when compared with PRP alone for patients with OA of the knee.[267] One meta-analysis demonstrated that combined intra-articular injection of mesenchymal stem cells (MSCs) with PRP improved pain and function scores at 6 months, but not at 12 months, compared with hyaluronic acid or PRP alone in patients with OA of the knee.[268]

Anti-nerve growth factor antibodies

Fasinumab, an anti-nerve growth factor monoclonal antibody, appeared to improve pain and function in a 36-week phase 2b/3 double-blind, placebo-controlled, randomised trial of patients with knee or hip OA with history of inadequate response or intolerance to analgesics.[269] The US National Library of Medicine clinical trials register suggests that there are no active clinical trials of fasinumab in patients with OA.[270] The US Food and Drug Administration's Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory Committee considered that the risk for joint destruction or rapidly progressive osteoarthritis (RPOA) associated with tanezumab, a humanised anti-nerve growth factor monoclonal antibody (for moderate to severe OA pain in adults for whom the use of other analgesics is ineffective or inappropriate) was too great. The European Medicines Agency's Committee for Medicinal Products for Human Use also recommended refusing a marketing application for tanezumab.