Main characteristics of the SR included
| Study | Population | Intervention and comparator | Outcomes | Quality |
| Knee osteoarthritis | ||||
| Rutjes et al7 | IC: RCTs EC: not stated. | HA vs sham or no intervention | Primary: pain intensity Secondary: function, SAEs, withdrawal due to AEs | High |
| Newberry et al22 | IC: RCTs, SRs, OS, and CS* EC: non-English language studies and conference abstracts. | HA vs PBO or other HA | Primary: delay or avoidance of TKR Secondary: function, QoL, number of AE | High |
| Jüni et al23 | IC: RCT of patients treated with GC either IA or subacromial. EC: RCT including only patients with inflammatory arthritis | IA GC vs sham, PBO or SOC | Primary: pain and function at 4–6 weeks Secondary: pain and function at subsequent time points, QoL, JSN, SAEs, withdrawals due to AEs | High |
| Ding et al24 | IC: RCTs reporting ≥1 of the outcomes of interest. EC: use of PRP or MSC+surgery or lack of a non-cell-based control | MSC vs PBO, HA or IAGC | WOMAC, KOOS, VAS, SAEs without a prespecified hierarchy | Moderate |
| Bannuru et al4 | IC: RCTs of patients treated with HA with data on safety outcomes EC: non-RCT studies | HA vs HA or PBO | Number of AEs, SAEs, withdrawals due to AEs without a prespecified hierarchy | Moderate |
| Bannuru et al6 | IC: RCTs with data for ≥1 outcome measure of pain. EC: studies not including pain outcomes of interest | HA vs IAGC | Primary: pain according to a prespecified hierarchy at different time-points | Moderate |
| Bannuru et al5 | IC: RCTs of patients with primary KOA with data on ≥2 interventions of interest and on ≥1 measure of pain, function or stiffness. EC: not stated | HA vs PBO HA vs IAGC IAGC vs PBO | Primary: pain at 3 months according to a prespecified hierarchy Secondary: function and stiffness at 3 months | Moderate |
| Kanchanatawan et al25 | IC: RCTs of adults with primary KOA with ≥1 of the outcomes of interest and enough data to extract and pool EC: not stated | PRP vs HA or PBO or sham | WOMAC total and subscores, Lequesne score, EuroQol-VAS, IKDC subjective scores, number of AEs without a prespecified hierarchy | Moderate |
| Xu et al26 | IC: RCTs with ≥30 randomised patients, ≥1 month follow-up, quantitative outcome assessment, <20% of dropouts EC: not stated | PRP vs HA, PBO | Pain and function (VAS, WOMAC, IKDC, Lequesne) without a prespecified hierarchy | Moderate |
| Dai et al27 | IC: RCTs comparing PRP vs controls for prespecified outcomes EC: not stated | PRP vs HA or PBO | Primary: WOMAC pain and function scores. Secondary: WOMAC total score, IKDC, Lequesne, frequency of AE | Moderate |
| Arroll and Goodyear-Smith28 | IC: PBO-controlled RCTs assessing the efficacy of IAGC EC: not stated | IAGC vs PBO | Primary: improvement of symptoms Secondary: pain, response to the OA research scale | Moderate |
| Shen et al29 | IC: RCT comparing any PRP vs another IAT with ≥12 w follow-up EC: studies without IA control group, other PRP or PRP+surgery | PRP vs HA or PBO | Primary: WOMAC pain, function and total at 3, 6, and 12 months Secondary: number of patients with AEs | Moderate |
| Trojian et al30 | IC: RCTs in English including outcomes of interest at ≥8 and <16 weeks. EC: studies comparing IA GC or HA vs surgical procedures | HA vs PBO or IAGC IAGC vs PBO | OMERACT-OARSI response rates, mean change from baseline in WOMAC pain, stiffness or function, frequency of AE. Without hierarchy | Moderate |
| Gallagher et al31 | IC: RCTs with PBO control, ≥12 m follow-up, data on structural changes EC: not stated | HA or SOC vs PBO† | Primary: changes in JSW or cartilage volume. Secondary: WOMAC total score, WOMAC pain or VAS pain | Moderate |
| Di et al32 | IC: English-written RCTs EC: unknown methodology or patients with additional conditions‡ | PRP vs HA | Primary: WOMAC, IKDC, KOOS, EQ-VAS, Tegner score. Secondary: frequency of AE between groups | Low |
| Trigkilidas and Anand35 | IC: RCTs with ≥1 outcome measure on pain or function; freely available as full text from specified sources§ EC: non-RCT and language other than English | HA vs PBO or IAGC | VAS pain, Lequesne, WOMAC without a prespecified hierarchy | Low |
| Lo et al33 | IC: Blinded—RCTs comparing HA (≥3 injections) vs PBO with data on pain and 8-week minimum follow-up and drop-out rate of <50% EC: not stated | HA vs PBO | Pain according to a prespecified hierarchy | Low |
| Hip osteoarthritis | ||||
| Ali et al36 | IC: RCTs, with clinical and functional data with any follow-up EC: studies on animals and technical notes | PRP vs HA | VAS pain, WOMAC total, and HHS without a prespecified hierarchy | Moderate |
| McCabe et al38 | IC: RCTs with patients with HOA (clinical and radiographic) EC: studies without a control group | IAGC vs PBO | Primary: pain according to a prespecified hierarchy Secondary: WOMAC function, Lequesne Index, safety profile | Moderate |
| Liao et al37 | IC: RCTs of patients with primary HOA EC: stated as the opposite to IC | HA vs PBO | Primary: self-reported pain according to a prespecified hierarchy Secondary: function, OMERACT-OARSI responder index | Moderate |
| Medina-Porqueres41 | IC: English or Spanish-written studies of PRP applied in isolation in ≥1 arm to patients with any grade of HOA as per the ACR criteria EC: studies including only children or animals; non-OA injuries, OA in other joints or previous surgery | PRP vs IA control (any) | Primary: VAS pain, HHS, and WOMAC function. Secondary: growth factor’s concentration, AE and imaging evaluations | Low |
| Ye et al42 | IC: RCTs comparing PRP with HA EC: studies without a control group, full-text versions or outcomes data | PRP vs HA | Primary: WOMAC total score, VAS pain, and Harris hip score (HHS) Secondary: n of AE | Low |
| Leite et al40 | IC: RCT with ≥1 of the outcomes of interest EC: RCT comparing HOA vs other sites and HA vs non-IA controls | HA vs IA-injection comparators | Primary: pain Secondary: QoL, OMERACT-OARSI Response, frequency of AEs | Low |
| Shoulder capsulitis | ||||
| Sun et al45 | IC: RCTs comparing IAGC vs no or sham injection or SOC EC: injection volume >0.10 mL (classified as IAGC+distention) | IAGC vs sham or SOC | Primary: VAS pain Secondary: passive external rotation, abduction, flexion, internal rotation,and functional scores and frequency of AEs | Moderate |
| Buchbinder et al43 | IC: RCTs of shoulder pain comparing IAGC vs PBO, another intervention or different IAGC dosages EC: pain duration <3 weeks, RA, polymyalgia rheumatica, and fracture | IAGC vs PBO, other interventions | Pain, ROM, function, strength, and return to work or school without a prespecified hierarchy | Moderate |
| Lee et al44 | IC: RCT of capsulitis (confirmed clinically or by US), clearly documenting IC and EC, symptom duration and follow-up >4 weeks EC: uncontrolled studies | HA vs SOC | Pain, ROM, and function/disability scores >1 month after administration, frequency of AEs without a prespecified hierarchy | Moderate |
| Rheumatoid arthritis | ||||
| Heuft-Dorenbosch et al46 | IC: RCTs of RA patients with knee arthritis, enough quality as per the Delphi list. Language restrictions applied¶ EC: not stated | Yttrium synovectomy vs PBO or TH | Knee circumference, ROM, fixed flexion, pain (Likert scale), subjective change, knee effusion, radiological assessment without prespecified hierarchy | Moderate |
| Silvinato and Bernardo34 | IC: RCTs of patients with RA and knee arthritis EC: not stated | MPA vs TA, TH, prednisolone | Primary: flare time at 24 weeks, Secondary: patient-reported pain and swelling, ROM, frequency of AEs | Low |
| Saito and Kotake47 | IC: English or Japanese-written RCTs of patients with RA and knee arthritis including pain assessment EC: studies with animals or only describing the injection technique | HA vs PBO | Primary: global pain measured with Likert scale at 1 week Secondary: inflammation measured with Likert scale. Condition of the knee with Likert scale, safety profile | Low |
*Only data from RCTs were retrieved for the analyses on the present study.
†Only data for the HA vs PBO comparison were retrieved.
‡Additional conditions included meniscal tears, inflammatory arthritis, among others.
§Free full-texts available from the Warwick University Library or Google Scholar.
¶Articles written in Dutch, English, French, German, or Spanish.
AE, adverse events; CS, case series; EC, exclusion criteria; EQ-VAS, Euro Quality of Life – Visual Analogue Scale; freq of AE, frequency of adverse events; GC, glucocorticoids; HA, hyaluronic acid; HHS, Harris Hip Score; HOA, hip osteoarthritis; IA, intra-articular; IAT, intra-articular therapies; IC, inclusion criteria; IKDC, International Knee Documentation Committee; JSN, joint space narrowing; JSW, joint space width; KOA, Knee Osteoarthritis Index; KOOS, Knee injury and Osteoarthritis Outcome Score ; MPA, methylprednisolone acetate; MSC, mesenchymal stem cells; OS, observational studies; PBO, placebo; PRP, platelet-rich plasma; QoL, quality of life; RCT, randomised-controlled trials; ROM, range of motion; SAE, serious adverse events; SoC, standard of care; TA, triamcinolone acetonide; TH, triamcinolone hexacetonide; TKR, total knee replacement; US, ultrasonography; VAS, Visual Analogue Scale; WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index.