Viscosupplementation for the treatment of osteoarthritis of the knee
N Bellamy, J Campbell, V Robinson, T Gee, R Bourne, G Wells, N Bellamy, J Campbell, V Robinson, T Gee, R Bourne, G Wells
Abstract
Background: Osteoarthritis (OA) is the most prevalent chronic joint disorder worldwide and is associated with significant pain and disability.
Objectives: To assess the effects of viscosupplementation in the treatment of OA of the knee. The products were hyaluronan and hylan derivatives (Adant, Arthrum H, Artz (Artzal, Supartz), BioHy (Arthrease, Euflexxa, Nuflexxa), Durolane, Fermathron, Go-On, Hyalgan, Hylan G-F 20 (Synvisc Hylan G-F 20), Hyruan, NRD-101 (Suvenyl), Orthovisc, Ostenil, Replasyn, SLM-10, Suplasyn, Synject and Zeel compositum).
Search strategy: MEDLINE (up to January (week 1) 2006 for update), EMBASE, PREMEDLINE, Current Contents up to July 2003, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched. Specialised journals and reference lists of identified randomised controlled trials (RCTs) and pertinent review articles up to December 2005 were handsearched.
Selection criteria: RCTs of viscosupplementation for the treatment of people with a diagnosis of OA of the knee were eligible. Single and double-blinded studies, placebo-based and comparative studies were eligible. At least one of the four OMERACT III core set outcome measures had to be reported (Bellamy 1997).
Data collection and analysis: Each trial was assessed independently by two reviewers for its methodological quality using a validated tool. All data were extracted by one reviewer and verified by a second reviewer . Continuous outcome measures were analysed as weighted mean differences (WMD) with 95% confidence intervals (CI). However, where different scales were used to measure the same outcome, standardized mean differences (SMD) were used. Dichotomous outcomes were analyzed by relative risk (RR).
Main results: Seventy-six trials with a median quality score of 3 (range 1 to 5) were identified. Follow-up periods varied between day of last injection and eighteen months. Forty trials included comparisons of hyaluronan/hylan and placebo (saline or arthrocentesis), ten trials included comparisons of intra-articular (IA) corticosteroids, six trials included comparisons of nonsteroidal anti-inflammatory drugs (NSAIDs), three trials included comparisons of physical therapy, two trials included comparisons of exercise, two trials included comparisons of arthroscopy, two trials included comparisons of conventional treatment, and fifteen trials included comparisons of other hyaluronans/hylan. The pooled analyses of the effects of viscosupplements against 'placebo' controls generally supported the efficacy of this class of intervention. In these same analyses, differential efficacy effects were observed for different products on different variables and at different timepoints. Of note is the 5 to 13 week post injection period which showed a percent improvement from baseline of 28 to 54% for pain and 9 to 32% for function. In general, comparable efficacy was noted against NSAIDs and longer-term benefits were noted in comparisons against IA corticosteroids. In general, few adverse events were reported in the hyaluronan/hylan trials included in these analyses.
Authors' conclusions: Based on the aforementioned analyses, viscosupplementation is an effective treatment for OA of the knee with beneficial effects: on pain, function and patient global assessment; and at different post injection periods but especially at the 5 to 13 week post injection period. It is of note that the magnitude of the clinical effect, as expressed by the WMD and standardised mean difference (SMD) from the RevMan 4.2 output, is different for different products, comparisons, timepoints, variables and trial designs. However, there are few randomised head-to-head comparisons of different viscosupplements and readers should be cautious, therefore, in drawing conclusions regarding the relative value of different products. The clinical effect for some products, against placebo, on some variables at some timepoints is in the moderate to large effect-size range. Readers should refer to relevant tables to review specific detail given the heterogeneity in effects across the product class and some discrepancies observed between the RevMan 4.2 analyses and the original publications. Overall, the analyses performed are positive for the HA class and particularly positive for some products with respect to certain variables and timepoints, such as pain on weight bearing at 5 to 13 weeks postinjection. In general, sample-size restrictions preclude any definitive comment on the safety of the HA class of products; however, within the constraints of the trial designs employed no major safety issues were detected. In some analyses viscosupplements were comparable in efficacy to systemic forms of active intervention, with more local reactions but fewer systemic adverse events. In other analyses HA products had more prolonged effects than IA corticosteroids. Overall, the aforementioned analyses support the use of the HA class of products in the treatment of knee OA.
Conflict of interest statement
The original review was externally supported by Genzyme Biosurgery [formerly Biomatrix, Inc] and Wyeth‐Ayerst as an unrestricted educational grant. Finances supported research staff to research this treatment area for all products, not just that manufactured by Genzyme BioSurgery [formerly Biomatrix, Inc]. The interpretation of the results are those of the reviewers who retain the right to publish.
Dr. Nicholas Bellamy and Dr. Robert Bourne participated in the Raynauld (Raynauld 2002) trial. Dr. Bellamy was a co‐investigator on the Steering Committee of the Raynauld (Raynauld 2002) trial, and previously provided consulting services to Biomatrix and Genzyme Inc.
Dr. Bourne was a clinical investigator in the Raynauld (Raynauld 2002) trial.
Product‐based analyses were circulated to each respective manufacturer prior to finalisation of the original review to permit any factual errors to be addressed. Comments were received from some but not all manufacturers.
Figures
Comparison 1 Adant versus Hyalgan, Outcome 1 Patient global assessment (number of patients excellent/good).
Comparison 1 Adant versus Hyalgan, Outcome 2 Safety: number of painful injections.
Comparison 2 Artz versus placebo, Outcome 1 Pain (100 mm VAS).
Comparison 2 Artz versus placebo, Outcome 2 Pain score (0‐3).
Comparison 2 Artz versus placebo, Outcome 3 WOMAC pain (0‐20 Likert).
Comparison 2 Artz versus placebo, Outcome 4 WOMAC function (0‐68 Likert).
Comparison 2 Artz versus placebo, Outcome 5 Lequesne Index (0‐24).
Comparison 2 Artz versus placebo, Outcome 6 Range of motion.
Comparison 2 Artz versus placebo, Outcome 7 Patient global assessment (number of patients improved).
Comparison 2 Artz versus placebo, Outcome 8 WOMAC stiffness (0‐8 Likert).
Comparison 2 Artz versus placebo, Outcome 9 Number of survivors (patients not requiring additional treatment for study knee) 45 to 52 weeks post‐injection.
Comparison 2 Artz versus placebo, Outcome 10 Number of clinical failures.
Comparison 2 Artz versus placebo, Outcome 11 Safety: total withdrawals overall.
Comparison 2 Artz versus placebo, Outcome 12 Safety: number of patients reporting adverse events (45 to 52 weeks post‐ injection).
Comparison 2 Artz versus placebo, Outcome 13 Safety: withdrawals due to adverse events.
Comparison 2 Artz versus placebo, Outcome 14 Safety: number of patients with local adverse reaction but study drug continued.
Comparison 2 Artz versus placebo, Outcome 15 Safety: number of adverse events probably/possibly related to treatment.
Comparison 2 Artz versus placebo, Outcome 16 Safety: number of serious adverse events (45 to 52 weeks post‐injection).
Comparison 2 Artz versus placebo, Outcome 17 Safety: total withdrawals overall (knees).
Comparison 3 Artzal versus Hylan G‐F 20 (Also see Hylan G‐F 20 versus hyaluronan, NRD‐101 versus Artz, SLM‐10 versus Artz), Outcome 1 Pain on weight bearing (0‐100 mm VAS).
Comparison 3 Artzal versus Hylan G‐F 20 (Also see Hylan G‐F 20 versus hyaluronan, NRD‐101 versus Artz, SLM‐10 versus Artz), Outcome 2 Lequesne Index (0‐24).
Comparison 3 Artzal versus Hylan G‐F 20 (Also see Hylan G‐F 20 versus hyaluronan, NRD‐101 versus Artz, SLM‐10 versus Artz), Outcome 3 Number of clinical failures.
Comparison 3 Artzal versus Hylan G‐F 20 (Also see Hylan G‐F 20 versus hyaluronan, NRD‐101 versus Artz, SLM‐10 versus Artz), Outcome 4 Number of survivors (patients not requiring additional treatment for study knee) (45 to 52 weeks post‐injectio.
Comparison 3 Artzal versus Hylan G‐F 20 (Also see Hylan G‐F 20 versus hyaluronan, NRD‐101 versus Artz, SLM‐10 versus Artz), Outcome 5 Safety: number of patients withdrawn due to adverse events (45 to 52 weeks post‐injection).
Comparison 3 Artzal versus Hylan G‐F 20 (Also see Hylan G‐F 20 versus hyaluronan, NRD‐101 versus Artz, SLM‐10 versus Artz), Outcome 6 Safety: number of adverse events related to treatment (45 to 52 weeks post‐ injection).
Comparison 3 Artzal versus Hylan G‐F 20 (Also see Hylan G‐F 20 versus hyaluronan, NRD‐101 versus Artz, SLM‐10 versus Artz), Outcome 7 Safety: number of patients reporting adverse events (45 to 52 weeks post‐ injection).
Comparison 4 BioHy (Arthrease, Euflexxa) versus placebo, Outcome 1 Safety: total withdrawals overall.
Comparison 4 BioHy (Arthrease, Euflexxa) versus placebo, Outcome 2 Safety: number of adverse events for injection site pain.
Comparison 5 BioHy (Arthrease, Euflexxa) versus Hylan G‐F 20 (Synvisc), Outcome 1 WOMAC pain (0‐100 mm VAS).
Comparison 5 BioHy (Arthrease, Euflexxa) versus Hylan G‐F 20 (Synvisc), Outcome 2 WOMAC physical function (0‐100 mm VAS).
Comparison 5 BioHy (Arthrease, Euflexxa) versus Hylan G‐F 20 (Synvisc), Outcome 3 WOMAC stiffness (0‐100 mm VAS).
Comparison 5 BioHy (Arthrease, Euflexxa) versus Hylan G‐F 20 (Synvisc), Outcome 4 WOMAC pain (number of patients symptom free: VAS score below 20 mm).
Comparison 5 BioHy (Arthrease, Euflexxa) versus Hylan G‐F 20 (Synvisc), Outcome 5 WOMAC function (number of patients symptom free: VAS score below 20 mm).
Comparison 5 BioHy (Arthrease, Euflexxa) versus Hylan G‐F 20 (Synvisc), Outcome 6 Patient assessment of treatment (number of patients very satisfied or satisfied).
Comparison 5 BioHy (Arthrease, Euflexxa) versus Hylan G‐F 20 (Synvisc), Outcome 7 Rescue medication usage (number of patients using acetaminophen).
Comparison 5 BioHy (Arthrease, Euflexxa) versus Hylan G‐F 20 (Synvisc), Outcome 8 Safety: total withdrawals overall.
Comparison 5 BioHy (Arthrease, Euflexxa) versus Hylan G‐F 20 (Synvisc), Outcome 9 Safety: withdrawals due to adverse events.
Comparison 5 BioHy (Arthrease, Euflexxa) versus Hylan G‐F 20 (Synvisc), Outcome 10 Safety: withdrawals due to lack of efficacy.
Comparison 5 BioHy (Arthrease, Euflexxa) versus Hylan G‐F 20 (Synvisc), Outcome 11 Safety: number of patients with serious adverse events.
Comparison 5 BioHy (Arthrease, Euflexxa) versus Hylan G‐F 20 (Synvisc), Outcome 12 Safety: number of patients with joint effusion.
Comparison 5 BioHy (Arthrease, Euflexxa) versus Hylan G‐F 20 (Synvisc), Outcome 13 Safety: number of patients reporting adverse events.
Comparison 6 Durolane versus placebo, Outcome 1 Responder: reduction in the WOMAC pain score of at least 40% with an absolute improvement of at least 5 points.
Comparison 6 Durolane versus placebo, Outcome 2 Responder: patients only with knee OA, reduction in WOMAC pain score of at least 40%, abs improvement 5 points.
Comparison 6 Durolane versus placebo, Outcome 3 WOMAC pain (change from baseline; 0 to 20 Likert).
Comparison 6 Durolane versus placebo, Outcome 4 WOMAC stiffness (change from baseline; 0 to 8 Likert).
Comparison 6 Durolane versus placebo, Outcome 5 WOMAC physical function (change from baseline; 0 to 68 Likert).
Comparison 6 Durolane versus placebo, Outcome 6 Safety: total withdrawals overall.
Comparison 6 Durolane versus placebo, Outcome 7 Safety: withdrawals due to inefficacy.
Comparison 6 Durolane versus placebo, Outcome 8 Safety: withdrawals due to adverse events.
Comparison 6 Durolane versus placebo, Outcome 9 Safety: number of patients affected by device‐related adverse events.
Comparison 6 Durolane versus placebo, Outcome 10 Safety: number of patients with adverse events related to injection only.
Comparison 6 Durolane versus placebo, Outcome 11 Safety: number of patients with non‐serious treatment‐related adverse events.
Comparison 6 Durolane versus placebo, Outcome 12 Safety: number of patients with non‐serious adverse events.
Comparison 6 Durolane versus placebo, Outcome 13 Safety: number of patients with treated unrelated adverse events.
Comparison 6 Durolane versus placebo, Outcome 14 Safety: number of patients with serious treatment‐unrelated adverse events.
Comparison 7 Fermathron versus Hyalart, Outcome 1 Pain (0‐100 mm VAS).
Comparison 7 Fermathron versus Hyalart, Outcome 2 Lequesne Index (0‐24).
Comparison 7 Fermathron versus Hyalart, Outcome 3 Patient global assessment (number of patients much better/better).
Comparison 7 Fermathron versus Hyalart, Outcome 4 Safety: number of related adverse events.
Comparison 8 Hyalgan versus placebo, Outcome 1 Pain on weight bearing (walking) (0‐100 mm VAS).
Comparison 8 Hyalgan versus placebo, Outcome 2 Pain spontaneous (0‐100 mm VAS).
Comparison 8 Hyalgan versus placebo, Outcome 3 Pain at rest (0‐100 mm VAS).
Comparison 8 Hyalgan versus placebo, Outcome 4 Pain at night (0‐100 mm VAS).
Comparison 8 Hyalgan versus placebo, Outcome 5 WOMAC pain (0‐100 mm VAS).
Comparison 8 Hyalgan versus placebo, Outcome 6 Number of joints improved for walking pain.
Comparison 8 Hyalgan versus placebo, Outcome 7 Number of joints improved for pain under load.
Comparison 8 Hyalgan versus placebo, Outcome 8 Number of knee joints without rest pain.
Comparison 8 Hyalgan versus placebo, Outcome 9 Number of knee joints without night pain.
Comparison 8 Hyalgan versus placebo, Outcome 10 Number of joints with improvement in pain on touch.
Comparison 8 Hyalgan versus placebo, Outcome 11 Number of patients with moderate/marked pain.
Comparison 8 Hyalgan versus placebo, Outcome 12 Pain (number of patients improved).
Comparison 8 Hyalgan versus placebo, Outcome 13 WOMAC function (0‐100 mm VAS).
Comparison 8 Hyalgan versus placebo, Outcome 14 Lequesne Index (0‐24).
Comparison 8 Hyalgan versus placebo, Outcome 15 Flexion (degrees).
Comparison 8 Hyalgan versus placebo, Outcome 16 Synovial fluid volume (ml).
Comparison 8 Hyalgan versus placebo, Outcome 17 Joint space width (mm).
Comparison 8 Hyalgan versus placebo, Outcome 18 Patient global assessment (number of patients improved).
Comparison 8 Hyalgan versus placebo, Outcome 19 Patient global assessment (number of joints fairly good/good/very good).
Comparison 8 Hyalgan versus placebo, Outcome 20 Safety: total withdrawals overall.
Comparison 8 Hyalgan versus placebo, Outcome 21 Safety: withdrawals due to lack of efficacy.
Comparison 8 Hyalgan versus placebo, Outcome 22 Safety: withdrawals due to painful injection.
Comparison 8 Hyalgan versus placebo, Outcome 23 Safety: number of patients with local adverse reaction and study drug discontinued.
Comparison 8 Hyalgan versus placebo, Outcome 24 Safety: number of patients with local adverse reaction but study drug continued.
Comparison 8 Hyalgan versus placebo, Outcome 25 Safety: number of patients discontinued due to adverse events.
Comparison 8 Hyalgan versus placebo, Outcome 26 Safety: number of patients with serious or severe adverse events.
Comparison 8 Hyalgan versus placebo, Outcome 27 Safety: number of knee joints with local adverse reaction.
Comparison 8 Hyalgan versus placebo, Outcome 28 Safety: number of patients with injection site pain or painful intra‐articular injection.
Comparison 8 Hyalgan versus placebo, Outcome 29 Safety: number of patients with local joint pain or swelling.
Comparison 8 Hyalgan versus placebo, Outcome 30 Safety: number of patients with local skin rash or ecchymosis.
Comparison 8 Hyalgan versus placebo, Outcome 31 Safety: number of patients with gastrointestinal complaints.
Comparison 8 Hyalgan versus placebo, Outcome 32 Safety: number of patients with pruritis (local).
Comparison 8 Hyalgan versus placebo, Outcome 33 Safety: number of patients with treatment related adverse events.
Comparison 8 Hyalgan versus placebo, Outcome 34 Safety: number of patients reporting adverse events.
Comparison 8 Hyalgan versus placebo, Outcome 35 Number of patients with none/slight/mild pain.
Comparison 8 Hyalgan versus placebo, Outcome 36 Joint space width (mm) (after three courses of treatment and stratified subgroups).
Comparison 9 Hyalgan versus arthroscopy, Outcome 1 Pain (0‐10 cm VAS).
Comparison 9 Hyalgan versus arthroscopy, Outcome 2 Knee Society Function scale.
Comparison 9 Hyalgan versus arthroscopy, Outcome 3 Lequesne Index (0‐24).
Comparison 9 Hyalgan versus arthroscopy, Outcome 4 Clinical outcome (number of patients requiring further intervention).
Comparison 9 Hyalgan versus arthroscopy, Outcome 5 Safety: total withdrawals overall.
Comparison 9 Hyalgan versus arthroscopy, Outcome 6 Safety: number of patients with pain at injection site.
Comparison 10 Hyalgan versus NSAID, Outcome 1 Pain after 50 foot walk (0‐100 mm VAS).
Comparison 10 Hyalgan versus NSAID, Outcome 2 Number of patients with moderate or marked pain.
Comparison 10 Hyalgan versus NSAID, Outcome 3 Number of patients with none/slight/mild pain.
Comparison 10 Hyalgan versus NSAID, Outcome 4 Safety: total withdrawals overall.
Comparison 10 Hyalgan versus NSAID, Outcome 5 Safety: withdrawals due to lack of efficacy.
Comparison 10 Hyalgan versus NSAID, Outcome 6 Safety: number of patients withdrawn due to gastrointestinal events.
Comparison 10 Hyalgan versus NSAID, Outcome 7 Safety: number of patients withdrawn due to injection site pain.
Comparison 10 Hyalgan versus NSAID, Outcome 8 Safety: number of patients with injection site pain.
Comparison 10 Hyalgan versus NSAID, Outcome 9 Safety: number of patients with local joint pain or swelling.
Comparison 10 Hyalgan versus NSAID, Outcome 10 Safety: number of patients with local skin rash.
Comparison 10 Hyalgan versus NSAID, Outcome 11 Safety: number of patients with gastrointestinal complaints.
Comparison 10 Hyalgan versus NSAID, Outcome 12 Safety: number of patients with pruritis (local).
Comparison 11 Hyalgan versus methylprednisolone acetate, Outcome 1 Spontaneous pain intensity (0‐100 mm VAS).
Comparison 11 Hyalgan versus methylprednisolone acetate, Outcome 2 Number of joints with moderate or severe walking pain.
Comparison 11 Hyalgan versus methylprednisolone acetate, Outcome 3 Number of patients with moderate or severe pain under load.
Comparison 11 Hyalgan versus methylprednisolone acetate, Outcome 4 Number of joints with moderate or severe pain under load.
Comparison 11 Hyalgan versus methylprednisolone acetate, Outcome 5 Number of patients with at least moderate or greater night pain.
Comparison 11 Hyalgan versus methylprednisolone acetate, Outcome 6 Number of patients with moderate or greater rest pain.
Comparison 11 Hyalgan versus methylprednisolone acetate, Outcome 7 Function: range of motion (flexion in degrees).
Comparison 11 Hyalgan versus methylprednisolone acetate, Outcome 8 Patient global (number of patients very good or good, excellent or /good).
Comparison 11 Hyalgan versus methylprednisolone acetate, Outcome 9 Safety: total withdrawals overall.
Comparison 11 Hyalgan versus methylprednisolone acetate, Outcome 10 Safety: number of patients withdrawn due to lack of efficacy.
Comparison 11 Hyalgan versus methylprednisolone acetate, Outcome 11 Safety: number of patients withdrawn due to adverse events.
Comparison 11 Hyalgan versus methylprednisolone acetate, Outcome 12 Safety: number of patients with local or systemic reactions.
Comparison 11 Hyalgan versus methylprednisolone acetate, Outcome 13 Safety: number of joints with local reactions but continued in trial.
Comparison 12 Hyalgan versus triamcinolone hexacetonide, Outcome 1 Pain on nominated activity (0‐100 mm VAS).
Comparison 12 Hyalgan versus triamcinolone hexacetonide, Outcome 2 Pain at rest (0‐100 mm VAS).
Comparison 12 Hyalgan versus triamcinolone hexacetonide, Outcome 3 Pain at night (0‐100 mm VAS).
Comparison 12 Hyalgan versus triamcinolone hexacetonide, Outcome 4 Safety: total withdrawals overall.
Comparison 12 Hyalgan versus triamcinolone hexacetonide, Outcome 5 Safety: wIthdrawals due to lack efficacy.
Comparison 12 Hyalgan versus triamcinolone hexacetonide, Outcome 6 Safety: wIthdrawals due to adverse events.
Comparison 13 Hyalgan versus mucopolysaccharide polysulfuric acid ester, Outcome 1 Pain (0‐30) change.
Comparison 13 Hyalgan versus mucopolysaccharide polysulfuric acid ester, Outcome 2 Function (0‐30) change.
Comparison 13 Hyalgan versus mucopolysaccharide polysulfuric acid ester, Outcome 3 Range of motion (0‐10) change.
Comparison 13 Hyalgan versus mucopolysaccharide polysulfuric acid ester, Outcome 4 Total Larson rating score (0‐77) change.
Comparison 13 Hyalgan versus mucopolysaccharide polysulfuric acid ester, Outcome 5 Patient global (number of patients symptom free or markedly improved).
Comparison 13 Hyalgan versus mucopolysaccharide polysulfuric acid ester, Outcome 6 Safety: total withdrawals overall.
Comparison 13 Hyalgan versus mucopolysaccharide polysulfuric acid ester, Outcome 7 Safety: adverse events due to study medication.
Comparison 14 (Hyalgan plus exercise plus ultrasound) versus control warmup exercise, Outcome 1 Pain (0‐10 cm VAS).
Comparison 14 (Hyalgan plus exercise plus ultrasound) versus control warmup exercise, Outcome 2 Lequesne Index (0‐26).
Comparison 14 (Hyalgan plus exercise plus ultrasound) versus control warmup exercise, Outcome 3 Range of motion (degrees).
Comparison 14 (Hyalgan plus exercise plus ultrasound) versus control warmup exercise, Outcome 4 Ambulation speed (metres per minute).
Comparison 14 (Hyalgan plus exercise plus ultrasound) versus control warmup exercise, Outcome 5 Safety: total withdrawals overall.
Comparison 15 (Hyalgan plus exercise plus ultrasound) versus exercise, Outcome 1 Pain (0‐10 cm VAS).
Comparison 15 (Hyalgan plus exercise plus ultrasound) versus exercise, Outcome 2 Lequesne Index (0‐26).
Comparison 15 (Hyalgan plus exercise plus ultrasound) versus exercise, Outcome 3 Range of motion (degrees).
Comparison 15 (Hyalgan plus exercise plus ultrasound) versus exercise, Outcome 4 Ambulation speed (metres per minute).
Comparison 15 (Hyalgan plus exercise plus ultrasound) versus exercise, Outcome 5 Safety: total withdrawals overall.
Comparison 16 (Hyalgan plus exercise plus ultrasound) versus (exercise plus ultrasound), Outcome 1 Pain (0‐10 cm VAS).
Comparison 16 (Hyalgan plus exercise plus ultrasound) versus (exercise plus ultrasound), Outcome 2 Lequesne Index (0‐26).
Comparison 16 (Hyalgan plus exercise plus ultrasound) versus (exercise plus ultrasound), Outcome 3 Range of motion (degrees).
Comparison 16 (Hyalgan plus exercise plus ultrasound) versus (exercise plus ultrasound), Outcome 4 Ambulation speed (metres per minute).
Comparison 16 (Hyalgan plus exercise plus ultrasound) versus (exercise plus ultrasound), Outcome 5 Safety: total withdrawals overall.
Comparison 17 Hyalgan versus conventional therapy (three courses of treatment), Outcome 1 Pain overall (0‐100 mm VAS).
Comparison 17 Hyalgan versus conventional therapy (three courses of treatment), Outcome 2 Lequesne Index (0‐24).
Comparison 17 Hyalgan versus conventional therapy (three courses of treatment), Outcome 3 Joint space width (mm).
Comparison 17 Hyalgan versus conventional therapy (three courses of treatment), Outcome 4 Quality of life (AIMS: total of 12 items).
Comparison 17 Hyalgan versus conventional therapy (three courses of treatment), Outcome 5 Arthroscopy overall assessment (0‐100 mm VAS).
Comparison 17 Hyalgan versus conventional therapy (three courses of treatment), Outcome 6 SFA scoring (0‐100 mm VAS).
Comparison 17 Hyalgan versus conventional therapy (three courses of treatment), Outcome 7 Safety: total withdrawals.
Comparison 18 Hyalgan versus Hylan G‐F 20, Outcome 1 Safety: number of patients with local reaction (acute inflammation and pain).
Comparison 19 Hyalgan versus Hyalgan, Outcome 1 Patient global (number of patients assessing response as satisfactory).
Comparison 20 Hylan G‐F 20 versus placebo, Outcome 1 Pain on weight bearing (0‐100 mm VAS).
Comparison 20 Hylan G‐F 20 versus placebo, Outcome 2 Pain walking (0‐100 mm VAS).
Comparison 20 Hylan G‐F 20 versus placebo, Outcome 3 WOMAC pain.
Comparison 20 Hylan G‐F 20 versus placebo, Outcome 4 Pain at night (0‐100 mm VAS).
Comparison 20 Hylan G‐F 20 versus placebo, Outcome 5 Pain at rest (0‐100 mm VAS).
Comparison 20 Hylan G‐F 20 versus placebo, Outcome 6 Pain overall (0‐100 mm VAS).
Comparison 20 Hylan G‐F 20 versus placebo, Outcome 7 WOMAC physical function.
Comparison 20 Hylan G‐F 20 versus placebo, Outcome 8 Lequesne Index (0‐24).
Comparison 20 Hylan G‐F 20 versus placebo, Outcome 9 Function: improvment in most painful knee movement (0‐100 mm VAS).
Comparison 20 Hylan G‐F 20 versus placebo, Outcome 10 15 metre walking time.
Comparison 20 Hylan G‐F 20 versus placebo, Outcome 11 WOMAC stiffness (2 to 10 Likert).
Comparison 20 Hylan G‐F 20 versus placebo, Outcome 12 Patient global assessment (0‐100 mm VAS; where 100 is worst severity).
Comparison 20 Hylan G‐F 20 versus placebo, Outcome 13 Patient global assessment (number of patients good or very good) 5 to 13 weeks post‐injection.
Comparison 20 Hylan G‐F 20 versus placebo, Outcome 14 Patient global evaluation of efficacy due to treatment.
Comparison 20 Hylan G‐F 20 versus placebo, Outcome 15 Physician global assessment (0‐100 mm VAS; where 100 is worst severity).
Comparison 20 Hylan G‐F 20 versus placebo, Outcome 16 Number of survivors (patients not requiring additional treatment for study knee).
Comparison 20 Hylan G‐F 20 versus placebo, Outcome 17 Number of clinical failures.
Comparison 20 Hylan G‐F 20 versus placebo, Outcome 18 Need for paracetamol (pill count).
Comparison 20 Hylan G‐F 20 versus placebo, Outcome 19 Safety: total withdrawals overall.
Comparison 20 Hylan G‐F 20 versus placebo, Outcome 20 Safety: number of patients withdrawn due to noncomplinance.
Comparison 20 Hylan G‐F 20 versus placebo, Outcome 21 Safety: number of patients with local reaction.
Comparison 20 Hylan G‐F 20 versus placebo, Outcome 22 Safety: number of patients with local adverse reactions but study drug continued.
Comparison 20 Hylan G‐F 20 versus placebo, Outcome 23 Safety: number of patients with one or more probable or possible related systemic adverse events.
Comparison 20 Hylan G‐F 20 versus placebo, Outcome 24 Safety: number of patients reporting systemic reactions.
Comparison 21 Hylan G‐F 20 versus NSAID, Outcome 1 Pain on motion (0‐100 mm VAS).
Comparison 21 Hylan G‐F 20 versus NSAID, Outcome 2 WOMAC pain (0‐100 mm VAS).
Comparison 21 Hylan G‐F 20 versus NSAID, Outcome 3 Pain at rest (0‐100 mm VAS).
Comparison 21 Hylan G‐F 20 versus NSAID, Outcome 4 Pain at night (0‐100 mm VAS).
Comparison 21 Hylan G‐F 20 versus NSAID, Outcome 5 Pain overall (0‐100 mm VAS).
Comparison 21 Hylan G‐F 20 versus NSAID, Outcome 6 WOMAC function (0‐100 mm VAS).
Comparison 21 Hylan G‐F 20 versus NSAID, Outcome 7 Lequesne Index (0‐24).
Comparison 21 Hylan G‐F 20 versus NSAID, Outcome 8 Patient overall assessment of treatment (number of patients excellent, very good, good).
Comparison 21 Hylan G‐F 20 versus NSAID, Outcome 9 Safety: total withdrawals overall.
Comparison 21 Hylan G‐F 20 versus NSAID, Outcome 10 Safety: number of patients with local reactions.
Comparison 21 Hylan G‐F 20 versus NSAID, Outcome 11 Safety: number of patients with probable or possible related systemic adverse events.
Comparison 21 Hylan G‐F 20 versus NSAID, Outcome 12 Safety: withdrawals due to adverse events.
Comparison 22 (Hylan G‐F 20 + NSAID + arthrocentesis) versus (NSAID + arthrocentesis), Outcome 1 Pain on motion (0‐100 mm VAS).
Comparison 22 (Hylan G‐F 20 + NSAID + arthrocentesis) versus (NSAID + arthrocentesis), Outcome 2 Pain at rest (0‐100 mm VAS).
Comparison 22 (Hylan G‐F 20 + NSAID + arthrocentesis) versus (NSAID + arthrocentesis), Outcome 3 Pain at night (0‐100 mm VAS).
Comparison 22 (Hylan G‐F 20 + NSAID + arthrocentesis) versus (NSAID + arthrocentesis), Outcome 4 Pain overall (0‐100 mm VAS).
Comparison 22 (Hylan G‐F 20 + NSAID + arthrocentesis) versus (NSAID + arthrocentesis), Outcome 5 Patient overall assessment of treatment (number of patients excellent, very good, or good).
Comparison 22 (Hylan G‐F 20 + NSAID + arthrocentesis) versus (NSAID + arthrocentesis), Outcome 6 Safety: total withdrawals overall.
Comparison 23 Hylan G‐F 20 versus betamethasone, Outcome 1 Safety: total withdrawals overall.
Comparison 23 Hylan G‐F 20 versus betamethasone, Outcome 2 Safety: wIthdrawals due to lack of efficacy.
Comparison 23 Hylan G‐F 20 versus betamethasone, Outcome 3 Safety: wIthdrawals due to acute local reaction.
Comparison 24 Hylan G‐F 20 versus triamcinolone hexacetonide, Outcome 1 WOMAC pain walking on a flat surface (Question 1: 0‐4 Likert).
Comparison 24 Hylan G‐F 20 versus triamcinolone hexacetonide, Outcome 2 WOMAC physical function subscale (0‐68 Likert).
Comparison 24 Hylan G‐F 20 versus triamcinolone hexacetonide, Outcome 3 WOMAC total score (0‐96 Likert).
Comparison 24 Hylan G‐F 20 versus triamcinolone hexacetonide, Outcome 4 Patient global overall assessment (0‐100 mm VAS).
Comparison 24 Hylan G‐F 20 versus triamcinolone hexacetonide, Outcome 5 Number of responders (greater than or equal to one category on WOMAC pain Q1).
Comparison 24 Hylan G‐F 20 versus triamcinolone hexacetonide, Outcome 6 Analgesic usage.
Comparison 24 Hylan G‐F 20 versus triamcinolone hexacetonide, Outcome 7 Safety: total withdrawals overall.
Comparison 24 Hylan G‐F 20 versus triamcinolone hexacetonide, Outcome 8 Safety: withdrawals due to adverse event.
Comparison 24 Hylan G‐F 20 versus triamcinolone hexacetonide, Outcome 9 Safety: withdrawals due to lack of efficacy.
Comparison 25 Hylan G‐F 20 versus physical therapy, Outcome 1 Spontaneous pain (0‐100 mm VAS).
Comparison 25 Hylan G‐F 20 versus physical therapy, Outcome 2 WOMAC pain.
Comparison 25 Hylan G‐F 20 versus physical therapy, Outcome 3 WOMAC physical function.
Comparison 25 Hylan G‐F 20 versus physical therapy, Outcome 4 SF‐36 pain.
Comparison 25 Hylan G‐F 20 versus physical therapy, Outcome 5 SF‐36 physical functioning.
Comparison 26 (Hylan G‐F 20 + physiotherapy) versus physiotherapy, Outcome 1 Lequesne Index (0‐24).
Comparison 26 (Hylan G‐F 20 + physiotherapy) versus physiotherapy, Outcome 2 Safety: total withdrawls overall.
Comparison 26 (Hylan G‐F 20 + physiotherapy) versus physiotherapy, Outcome 3 Safety: number of patients with adverse events.
Comparison 27 Hylan G‐F 20 versus progressive knee exercises, Outcome 1 Pain during activity.
Comparison 27 Hylan G‐F 20 versus progressive knee exercises, Outcome 2 Pain at rest.
Comparison 27 Hylan G‐F 20 versus progressive knee exercises, Outcome 3 Pain during climbing stairs.
Comparison 27 Hylan G‐F 20 versus progressive knee exercises, Outcome 4 Pain during transfer activity.
Comparison 27 Hylan G‐F 20 versus progressive knee exercises, Outcome 5 Walking distance.
Comparison 27 Hylan G‐F 20 versus progressive knee exercises, Outcome 6 Range of motion (degrees).
Comparison 27 Hylan G‐F 20 versus progressive knee exercises, Outcome 7 Hospital for Special Surgery Knee Score (100 points).
Comparison 27 Hylan G‐F 20 versus progressive knee exercises, Outcome 8 Safety: total withdrawals overall.
Comparison 28 Hylan G‐F 20 versus appropriate care, Outcome 1 WOMAC pain (0‐20 Likert).
Comparison 28 Hylan G‐F 20 versus appropriate care, Outcome 2 WOMAC pain (0‐100 mm VAS).
Comparison 28 Hylan G‐F 20 versus appropriate care, Outcome 3 Pain on walking (0‐100 mm VAS).
Comparison 28 Hylan G‐F 20 versus appropriate care, Outcome 4 WOMAC function (0‐68 Likert).
Comparison 28 Hylan G‐F 20 versus appropriate care, Outcome 5 WOMAC function (0‐100 mm VAS).
Comparison 28 Hylan G‐F 20 versus appropriate care, Outcome 6 Lequesne Index (0‐24).
Comparison 28 Hylan G‐F 20 versus appropriate care, Outcome 7 WOMAC total score (0‐100 mm VAS).
Comparison 28 Hylan G‐F 20 versus appropriate care, Outcome 8 Patient global assessment (number of patients improved in study knee).
Comparison 28 Hylan G‐F 20 versus appropriate care, Outcome 9 Patient global evaluation of effectiveness (good or satisfactory).
Comparison 28 Hylan G‐F 20 versus appropriate care, Outcome 10 Number of responders (20% decrease in pain on walking).
Comparison 28 Hylan G‐F 20 versus appropriate care, Outcome 11 Safety: total withdrawals overall.
Comparison 28 Hylan G‐F 20 versus appropriate care, Outcome 12 Safety: wIthdrawals due to lack of effectiveness.
Comparison 28 Hylan G‐F 20 versus appropriate care, Outcome 13 Safety: wIthdrawals due to adverse events.
Comparison 28 Hylan G‐F 20 versus appropriate care, Outcome 14 Safety: number of patients reporting mild, moderate or severe side effects at month 12.
Comparison 28 Hylan G‐F 20 versus appropriate care, Outcome 15 Safety: total number of patients reporting side effects from baseline.
Comparison 28 Hylan G‐F 20 versus appropriate care, Outcome 16 Safety: number of patients with gastrointestinal adverse events.
Comparison 29 Hylan G‐F 20 versus gaseous oxygen, Outcome 1 Pain under load (0‐100 mm VAS).
Comparison 29 Hylan G‐F 20 versus gaseous oxygen, Outcome 2 Pain at rest (0‐100 mm VAS).
Comparison 29 Hylan G‐F 20 versus gaseous oxygen, Outcome 3 WOMAC pain (0‐20 Likert).
Comparison 29 Hylan G‐F 20 versus gaseous oxygen, Outcome 4 WOMAC physical function (0‐68 Likert).
Comparison 29 Hylan G‐F 20 versus gaseous oxygen, Outcome 5 WOMAC stiffness (0‐8 Likert).
Comparison 29 Hylan G‐F 20 versus gaseous oxygen, Outcome 6 Safety: total number of withdrawals.
Comparison 29 Hylan G‐F 20 versus gaseous oxygen, Outcome 7 Safety: number of patients having total knee replacements.
Comparison 30 Hylan G‐F 20 versus hyaluronan (Also see Artzal, BioHy (Arthrease), Hyalgan and Orthovisc versus Hylan G‐F 20), Outcome 1 Pain on weight bearing (0‐100 mm VAS).
Comparison 30 Hylan G‐F 20 versus hyaluronan (Also see Artzal, BioHy (Arthrease), Hyalgan and Orthovisc versus Hylan G‐F 20), Outcome 2 Pain at night (0‐100 mm VAS).
Comparison 30 Hylan G‐F 20 versus hyaluronan (Also see Artzal, BioHy (Arthrease), Hyalgan and Orthovisc versus Hylan G‐F 20), Outcome 3 Function: improvement in knee movement (0‐100 mm VAS).
Comparison 30 Hylan G‐F 20 versus hyaluronan (Also see Artzal, BioHy (Arthrease), Hyalgan and Orthovisc versus Hylan G‐F 20), Outcome 4 Patient global evaluation of treatment efficacy (improvement: 0‐100 mm VAS).
Comparison 30 Hylan G‐F 20 versus hyaluronan (Also see Artzal, BioHy (Arthrease), Hyalgan and Orthovisc versus Hylan G‐F 20), Outcome 5 Safety: total withdrawals overall.
Comparison 30 Hylan G‐F 20 versus hyaluronan (Also see Artzal, BioHy (Arthrease), Hyalgan and Orthovisc versus Hylan G‐F 20), Outcome 6 Safety: number of patients with local reactions.
Comparison 31 NRD‐101 (Suvenyl) versus placebo (saline plus oral placebo), Outcome 1 Pain (0‐100 mm VAS) change between baseline and 45 to 52 weeks post‐injection.
Comparison 31 NRD‐101 (Suvenyl) versus placebo (saline plus oral placebo), Outcome 2 Lequesne Index (0‐100 modified scale) change between baseline and 45 to 52 weeks post‐injection.
Comparison 31 NRD‐101 (Suvenyl) versus placebo (saline plus oral placebo), Outcome 3 Patient global assessment (0‐100 mm VAS) change between baseline and 45 to 52 weeks post‐injection.
Comparison 31 NRD‐101 (Suvenyl) versus placebo (saline plus oral placebo), Outcome 4 Percentage of painful days (0‐100 mm VAS) change between baseline and 45 to 52 weeks post‐injection.
Comparison 31 NRD‐101 (Suvenyl) versus placebo (saline plus oral placebo), Outcome 5 Patient assessment of treatment efficacy (no. of patients rating very good or good versus mod, bad or very bad.
Comparison 31 NRD‐101 (Suvenyl) versus placebo (saline plus oral placebo), Outcome 6 Joint space width (percentage of progressors: joint space narrowing greater than 0.5 mm).
Comparison 31 NRD‐101 (Suvenyl) versus placebo (saline plus oral placebo), Outcome 7 Safety: total withdrawals overall.
Comparison 31 NRD‐101 (Suvenyl) versus placebo (saline plus oral placebo), Outcome 8 Safety: withdrawals due to inefficacy.
Comparison 31 NRD‐101 (Suvenyl) versus placebo (saline plus oral placebo), Outcome 9 Safety: number of withdrawals due to adverse events.
Comparison 31 NRD‐101 (Suvenyl) versus placebo (saline plus oral placebo), Outcome 10 Safety: number of patients reporting knee pain during or after IA injection.
Comparison 31 NRD‐101 (Suvenyl) versus placebo (saline plus oral placebo), Outcome 11 Safety: number of patients reporting diarrhoea.
Comparison 32 NRD‐101 (Suvenyl) versus Diacerein, Outcome 1 Pain (0‐100 mm VAS) change between baseline and 45 to 52 weeks post‐injection.
Comparison 32 NRD‐101 (Suvenyl) versus Diacerein, Outcome 2 Lequesne Index (0‐100 modified scale) change between baseline and 45 to 52 weeks post‐injection.
Comparison 32 NRD‐101 (Suvenyl) versus Diacerein, Outcome 3 Patient global assessment (0‐100 mm VAS) change between baseline and 45 to 52 weeks post‐injection.
Comparison 32 NRD‐101 (Suvenyl) versus Diacerein, Outcome 4 Percentage of painful days (0‐100 mm VAS) change between baseline and 45 to 52 weeks post‐injection.
Comparison 32 NRD‐101 (Suvenyl) versus Diacerein, Outcome 5 Patient assessment of treatment efficacy (no. of patients rating very good or good versus mod, bad or very bad.
Comparison 32 NRD‐101 (Suvenyl) versus Diacerein, Outcome 6 Joint space width (percentage progressors: joint space narrowing greater than 0.5 mm).
Comparison 32 NRD‐101 (Suvenyl) versus Diacerein, Outcome 7 Safety: total withdrawals overall.
Comparison 32 NRD‐101 (Suvenyl) versus Diacerein, Outcome 8 Safety: withdrawals due to inefficacy.
Comparison 32 NRD‐101 (Suvenyl) versus Diacerein, Outcome 9 Safety: number of withdrawlals due to adverse events.
Comparison 32 NRD‐101 (Suvenyl) versus Diacerein, Outcome 10 Safety: number of patients reporting knee pain during or after IA injection.
Comparison 32 NRD‐101 (Suvenyl) versus Diacerein, Outcome 11 Safety: number of patients reporting diarrhoea.
Comparison 33 NRD‐101 (Suvenyl) versus Artz (end of treatment), Outcome 1 Spontaneous pain (number of patients improved).
Comparison 33 NRD‐101 (Suvenyl) versus Artz (end of treatment), Outcome 2 Pain during the night (number of patients improved).
Comparison 33 NRD‐101 (Suvenyl) versus Artz (end of treatment), Outcome 3 Pressure pain (number of patients improved).
Comparison 33 NRD‐101 (Suvenyl) versus Artz (end of treatment), Outcome 4 Passive movement pain (number of patients improved).
Comparison 33 NRD‐101 (Suvenyl) versus Artz (end of treatment), Outcome 5 Passive flexion (degrees).
Comparison 33 NRD‐101 (Suvenyl) versus Artz (end of treatment), Outcome 6 Passive extension (degrees).
Comparison 33 NRD‐101 (Suvenyl) versus Artz (end of treatment), Outcome 7 Patient global assessment.
Comparison 33 NRD‐101 (Suvenyl) versus Artz (end of treatment), Outcome 8 Safety: total withdrawals overall.
Comparison 33 NRD‐101 (Suvenyl) versus Artz (end of treatment), Outcome 9 Safety: number of adverse events.
Comparison 34 Orthovisc versus placebo, Outcome 1 WOMAC pain (5 to 25 Likert).
Comparison 34 Orthovisc versus placebo, Outcome 2 WOMAC pain (number of patients who improved).
Comparison 34 Orthovisc versus placebo, Outcome 3 WOMAC pain (number of patients who achieved greater than 5 unit improvement (relative to baseline score)).
Comparison 34 Orthovisc versus placebo, Outcome 4 Number of patients with a 20% improvement from baseline in WOMAC pain score.
Comparison 34 Orthovisc versus placebo, Outcome 5 Number of patients with a 40% improvement from baseline in WOMAC pain score.
Comparison 34 Orthovisc versus placebo, Outcome 6 Number of patients with a 50% improvement from baseline in WOMAC pain score.
Comparison 34 Orthovisc versus placebo, Outcome 7 WOMAC pain on standing (0 to 100 mm VAS; change from baseline).
Comparison 34 Orthovisc versus placebo, Outcome 8 WOMAC physical function (17 to 85 Likert).
Comparison 34 Orthovisc versus placebo, Outcome 9 Range of motion: flexion (degrees).
Comparison 34 Orthovisc versus placebo, Outcome 10 25 metre walking time (sec).
Comparison 34 Orthovisc versus placebo, Outcome 11 Knee circumference (mm).
Comparison 34 Orthovisc versus placebo, Outcome 12 WOMAC stiffness (2 to 10 Likert).
Comparison 34 Orthovisc versus placebo, Outcome 13 WOMAC total score (0 to 100 mm VAS; change from baseline).
Comparison 34 Orthovisc versus placebo, Outcome 14 Patient global assessment (0 to 100 mm VAS; where 100 is worst severity).
Comparison 34 Orthovisc versus placebo, Outcome 15 Patient global assessment (0 to 100 mm VAS; change from baseline).
Comparison 34 Orthovisc versus placebo, Outcome 16 Patient global assessment (number patients rating treatment as effective or very effective).
Comparison 34 Orthovisc versus placebo, Outcome 17 Physician global assessment (0 to 100 mm VAS; where 100 is worst severity).
Comparison 34 Orthovisc versus placebo, Outcome 18 Physician global assessment (0 to 100 VAS; change from baseline).
Comparison 34 Orthovisc versus placebo, Outcome 19 Synovial fluid effusion volume (ml).
Comparison 34 Orthovisc versus placebo, Outcome 20 Interleukin 6 level in the synovial fluid (pg/ml).
Comparison 34 Orthovisc versus placebo, Outcome 21 Interleukin 8 level in the synovial fluid (pg/ml).
Comparison 34 Orthovisc versus placebo, Outcome 22 Tumor necrosis factor alpha levels in synovial fluid.
Comparison 34 Orthovisc versus placebo, Outcome 23 Safety: total withdrawals overall.
Comparison 34 Orthovisc versus placebo, Outcome 24 Safety: withdrawals due to lack of efficacy.
Comparison 34 Orthovisc versus placebo, Outcome 25 Safety: number of patients with treatment related adverse events.
Comparison 34 Orthovisc versus placebo, Outcome 26 Safety: number of patients withdrawn due to noncompliance.
Comparison 34 Orthovisc versus placebo, Outcome 27 Safety: number of patients with reported musculoskeletal adverse events.
Comparison 34 Orthovisc versus placebo, Outcome 28 Safety: number of patients with general body adverse events.
Comparison 34 Orthovisc versus placebo, Outcome 29 Safety: number of patients with local skin rash.
Comparison 34 Orthovisc versus placebo, Outcome 30 Safety: number patients with gastrointestinal complaints.
Comparison 34 Orthovisc versus placebo, Outcome 31 Safety: number of patients with reported respiratory adverse events.
Comparison 34 Orthovisc versus placebo, Outcome 32 Safety: number of patients with nervous system adverse events.
Comparison 34 Orthovisc versus placebo, Outcome 33 Safety: number of patients with urinary adverse events.
Comparison 34 Orthovisc versus placebo, Outcome 34 Safety: number of patients withdrawn due to local adverse events.
Comparison 35 Orthovisc versus betamethasone, Outcome 1 WOMAC function (0‐100 mm VAS).
Comparison 35 Orthovisc versus betamethasone, Outcome 2 Flexion (degrees).
Comparison 35 Orthovisc versus betamethasone, Outcome 3 Patient global assessment (number of patients good or very good).
Comparison 35 Orthovisc versus betamethasone, Outcome 4 Safety: total withdrawals overall.
Comparison 35 Orthovisc versus betamethasone, Outcome 5 Safety: number of patients withdrawn due to adverse events.
Comparison 35 Orthovisc versus betamethasone, Outcome 6 Safety: number of patients with local adverse events.
Comparison 35 Orthovisc versus betamethasone, Outcome 7 Safety: number of patients with systemic adverse events.
Comparison 36 Orthovisc versus 6‐methylprednisolone acetate, Outcome 1 Pain on weight bearing (0‐100 mm VAS).
Comparison 36 Orthovisc versus 6‐methylprednisolone acetate, Outcome 2 Pain at rest (0‐100 mm VAS).
Comparison 36 Orthovisc versus 6‐methylprednisolone acetate, Outcome 3 Pain on walking (0‐100 mm VAS).
Comparison 36 Orthovisc versus 6‐methylprednisolone acetate, Outcome 4 Lequesne Index (0‐24).
Comparison 36 Orthovisc versus 6‐methylprednisolone acetate, Outcome 5 Flexion (active range in degrees).
Comparison 36 Orthovisc versus 6‐methylprednisolone acetate, Outcome 6 Safety: total withdrawals overall.
Comparison 36 Orthovisc versus 6‐methylprednisolone acetate, Outcome 7 Safety: number of patients withdrawn due to increased pain.
Comparison 36 Orthovisc versus 6‐methylprednisolone acetate, Outcome 8 Safety: number of patients reporting musculoskeletal adverse events.
Comparison 36 Orthovisc versus 6‐methylprednisolone acetate, Outcome 9 Safety: number of patients reporting skin adverse events.
Comparison 36 Orthovisc versus 6‐methylprednisolone acetate, Outcome 10 Safety: number of patients reporting gastrointestinal adverse events.
Comparison 36 Orthovisc versus 6‐methylprednisolone acetate, Outcome 11 Safety: number of patients reporting general adverse events.
Comparison 36 Orthovisc versus 6‐methylprednisolone acetate, Outcome 12 Safety: number of patients reporting knee pain after injection.
Comparison 37 Orthovisc versus (Orthovisc plus triamcinolone acetonide), Outcome 1 Pain (0‐100 mm VAS).
Comparison 37 Orthovisc versus (Orthovisc plus triamcinolone acetonide), Outcome 2 WOMAC pain (0‐20 Likert).
Comparison 37 Orthovisc versus (Orthovisc plus triamcinolone acetonide), Outcome 3 WOMAC physical function (0‐68 Likert).
Comparison 37 Orthovisc versus (Orthovisc plus triamcinolone acetonide), Outcome 4 50 foot walking time (seconds).
Comparison 37 Orthovisc versus (Orthovisc plus triamcinolone acetonide), Outcome 5 Range of motion (degrees).
Comparison 37 Orthovisc versus (Orthovisc plus triamcinolone acetonide), Outcome 6 WOMAC stiffness (0‐8 Likert).
Comparison 37 Orthovisc versus (Orthovisc plus triamcinolone acetonide), Outcome 7 WOMAC total score (0‐96 Likert).
Comparison 37 Orthovisc versus (Orthovisc plus triamcinolone acetonide), Outcome 8 Safety: total withdrawals overall.
Comparison 37 Orthovisc versus (Orthovisc plus triamcinolone acetonide), Outcome 9 Safety: withdrawals due to lack of efficacy.
Comparison 37 Orthovisc versus (Orthovisc plus triamcinolone acetonide), Outcome 10 Safety: number of patients reporting adverse events (local reactions).
Comparison 38 Orthovisc versus (Orthovisc plus lidocaine trigger point injection)(1 week post‐injection), Outcome 1 Pain at rest (0 to 4 point scale).
Comparison 38 Orthovisc versus (Orthovisc plus lidocaine trigger point injection)(1 week post‐injection), Outcome 2 Pain/restrictions walking (0 to 4 point scale).
Comparison 38 Orthovisc versus (Orthovisc plus lidocaine trigger point injection)(1 week post‐injection), Outcome 3 Pain/restrictions going up or down stairs (0 to 4 point scale).
Comparison 38 Orthovisc versus (Orthovisc plus lidocaine trigger point injection)(1 week post‐injection), Outcome 4 Range of motion (degrees).
Comparison 38 Orthovisc versus (Orthovisc plus lidocaine trigger point injection)(1 week post‐injection), Outcome 5 Safety: total withdrawals overall.
Comparison 39 Orthovisc versus physical therapy, Outcome 1 Spontaneous pain (0‐100 mm VAS).
Comparison 39 Orthovisc versus physical therapy, Outcome 2 WOMAC pain.
Comparison 39 Orthovisc versus physical therapy, Outcome 3 WOMAC physical function.
Comparison 39 Orthovisc versus physical therapy, Outcome 4 SF‐36 pain.
Comparison 39 Orthovisc versus physical therapy, Outcome 5 SF‐36 physical functioning.
Comparison 40 (Orthovisc + physiotherapy) versus physiotherapy, Outcome 1 Activity pain (0‐100 mm VAS).
Comparison 40 (Orthovisc + physiotherapy) versus physiotherapy, Outcome 2 Spontaneous pain (0‐100 mm VAS).
Comparison 40 (Orthovisc + physiotherapy) versus physiotherapy, Outcome 3 Night pain (0‐100 mm VAS).
Comparison 40 (Orthovisc + physiotherapy) versus physiotherapy, Outcome 4 Lequesne (0‐24).
Comparison 40 (Orthovisc + physiotherapy) versus physiotherapy, Outcome 5 25 m walk time (sec).
Comparison 40 (Orthovisc + physiotherapy) versus physiotherapy, Outcome 6 Flexion (degrees).
Comparison 40 (Orthovisc + physiotherapy) versus physiotherapy, Outcome 7 Patient global assessment (number of patients evaluating treatment as effective or very effective).
Comparison 40 (Orthovisc + physiotherapy) versus physiotherapy, Outcome 8 Safety: total withdrawals overall.
Comparison 40 (Orthovisc + physiotherapy) versus physiotherapy, Outcome 9 Safety: number of patients with local reactions.
Comparison 40 (Orthovisc + physiotherapy) versus physiotherapy, Outcome 10 Safety: number of patients withdrawn due to adverse events.
Comparison 40 (Orthovisc + physiotherapy) versus physiotherapy, Outcome 11 Safety: number of patients with systemic adverse events.
Comparison 41 (Orthovisc + physiotherapy) versus (Hylan G‐F 20 + physiotherapy), Outcome 1 Lequesne Index (0‐24).
Comparison 42 Orthovisc versus hylan G‐F 20, Outcome 1 WOMAC pain (0‐20 or 5‐25 Likert).
Comparison 42 Orthovisc versus hylan G‐F 20, Outcome 2 Spontaneous pain (0‐100 mm VAS).
Comparison 42 Orthovisc versus hylan G‐F 20, Outcome 3 SF‐36 pain.
Comparison 42 Orthovisc versus hylan G‐F 20, Outcome 4 Hospital for Special Surgery Knee Score.
Comparison 42 Orthovisc versus hylan G‐F 20, Outcome 5 Pain during activity (Hospital for Special Surgery).
Comparison 42 Orthovisc versus hylan G‐F 20, Outcome 6 Pain at rest (Hospital for Special Surgery).
Comparison 42 Orthovisc versus hylan G‐F 20, Outcome 7 Pain during climbing stairs (Hospital for Special Surgery).
Comparison 42 Orthovisc versus hylan G‐F 20, Outcome 8 Pain during transfer activity (Hospital for Special Surgery).
Comparison 42 Orthovisc versus hylan G‐F 20, Outcome 9 WOMAC physical function (0‐68 or 17‐85 Likert).
Comparison 42 Orthovisc versus hylan G‐F 20, Outcome 10 SF‐36 physical functioning.
Comparison 42 Orthovisc versus hylan G‐F 20, Outcome 11 Range of motion (degrees).
Comparison 42 Orthovisc versus hylan G‐F 20, Outcome 12 Walking distance.
Comparison 42 Orthovisc versus hylan G‐F 20, Outcome 13 Patient global assessment (0‐100 mm VAS where 100 is worst severity).
Comparison 42 Orthovisc versus hylan G‐F 20, Outcome 14 Physician global assessment (0‐100 mm VAS where 100 is worst severity).
Comparison 42 Orthovisc versus hylan G‐F 20, Outcome 15 WOMAC stiffness (0‐8 or 2‐10 Likert).
Comparison 42 Orthovisc versus hylan G‐F 20, Outcome 16 Synovial fluid intercellular adhesion molecule‐1 (ICAM‐1).
Comparison 42 Orthovisc versus hylan G‐F 20, Outcome 17 Synovial fluid vascular cell adhesion molecule‐1 (VCAM‐1).
Comparison 42 Orthovisc versus hylan G‐F 20, Outcome 18 Safety: total withdrawals overall.
Comparison 42 Orthovisc versus hylan G‐F 20, Outcome 19 Safety: withdrawals due to lack of efficacy.
Comparison 42 Orthovisc versus hylan G‐F 20, Outcome 20 Safety: number of patients with local adverse event.
Comparison 42 Orthovisc versus hylan G‐F 20, Outcome 21 Safety: withdrawals due to noncompliance.
Comparison 43 Orthovisc versus Orthovisc, Outcome 1 WOMAC total score (0 to 100 mm VAS; change from baseline).
Comparison 43 Orthovisc versus Orthovisc, Outcome 2 Patient global assessment (0 to 100 mm VAS; change from baseline).
Comparison 43 Orthovisc versus Orthovisc, Outcome 3 Physician global assessment (0 to 100 mm VAS; change from baseline).
Comparison 43 Orthovisc versus Orthovisc, Outcome 4 WOMAC pain on standing (0 to 100 mm VAS; change from baseline).
Comparison 43 Orthovisc versus Orthovisc, Outcome 5 Number of patients with a 20% improvement from baseline in WOMAC pain score.
Comparison 43 Orthovisc versus Orthovisc, Outcome 6 Number of patients with a 40% improvement from baseline in WOMAC pain score.
Comparison 43 Orthovisc versus Orthovisc, Outcome 7 Number of patients with a 50% improvement from baseline in WOMAC pain score.
Comparison 43 Orthovisc versus Orthovisc, Outcome 8 Safety: total withdrawals overall.
Comparison 43 Orthovisc versus Orthovisc, Outcome 9 Safety: total withdrawals due to lack of efficacy.
Comparison 43 Orthovisc versus Orthovisc, Outcome 10 Safety: number of patients reporting adverse events.
Comparison 43 Orthovisc versus Orthovisc, Outcome 11 Safety: number of patients with gastrointestinal adverse events.
Comparison 43 Orthovisc versus Orthovisc, Outcome 12 Safety: number of patients with general body adverse events.
Comparison 43 Orthovisc versus Orthovisc, Outcome 13 Safety: number of patients with infections.
Comparison 43 Orthovisc versus Orthovisc, Outcome 14 Safety: number of patients with musculoskeletal adverse events.
Comparison 43 Orthovisc versus Orthovisc, Outcome 15 Safety: number of patients with nervous system adverse events.
Comparison 43 Orthovisc versus Orthovisc, Outcome 16 Safety: number of patients with respiratory adverse events.
Comparison 43 Orthovisc versus Orthovisc, Outcome 17 Safety: number of patients with skin adverse events.
Comparison 44 Replasyn versus placebo, Outcome 1 Safety: Number of patients with local adverse reaction but study drug continued.
Comparison 45 SLM‐10 versus Artz (end of treatment), Outcome 1 Pain in movement (number of patients improved).
Comparison 45 SLM‐10 versus Artz (end of treatment), Outcome 2 Pain when resting (number of patients improved).
Comparison 45 SLM‐10 versus Artz (end of treatment), Outcome 3 Pressure pain (number of patients improved).
Comparison 45 SLM‐10 versus Artz (end of treatment), Outcome 4 Patient global assessment (number of patients better or much better).
Comparison 45 SLM‐10 versus Artz (end of treatment), Outcome 5 Safety: total withdrawals overall.
Comparison 45 SLM‐10 versus Artz (end of treatment), Outcome 6 Safety: local adverse events related to study drug resulting in withdrawals.
Comparison 45 SLM‐10 versus Artz (end of treatment), Outcome 7 Safety: local adverse events no specific causal relationship to study drug and continuation in trial.
Comparison 46 Suplasyn versus placebo: 1 week post‐injection, Outcome 1 Pain after walking (0‐10 cm VAS).
Comparison 46 Suplasyn versus placebo: 1 week post‐injection, Outcome 2 WOMAC pain (0‐10 cm VAS).
Comparison 46 Suplasyn versus placebo: 1 week post‐injection, Outcome 3 Pain at rest (0‐10 cm VAS).
Comparison 46 Suplasyn versus placebo: 1 week post‐injection, Outcome 4 WOMAC function (0‐10 cm VAS).
Comparison 46 Suplasyn versus placebo: 1 week post‐injection, Outcome 5 Walk time (sec).
Comparison 46 Suplasyn versus placebo: 1 week post‐injection, Outcome 6 Safety: total withdrawals overall.
Comparison 47 Suplasyn versus NSAID: 1 week post‐injection, Outcome 1 Pain after walking (0‐10 cm VAS).
Comparison 47 Suplasyn versus NSAID: 1 week post‐injection, Outcome 2 WOMAC pain (0‐10 cm VAS).
Comparison 47 Suplasyn versus NSAID: 1 week post‐injection, Outcome 3 Pain at rest (0‐10 cm VAS).
Comparison 47 Suplasyn versus NSAID: 1 week post‐injection, Outcome 4 WOMAC function (0‐10 cm VAS).
Comparison 47 Suplasyn versus NSAID: 1 week post‐injection, Outcome 5 Walk time (sec).
Comparison 47 Suplasyn versus NSAID: 1 week post‐injection, Outcome 6 Safety: total withdrawals overall.
Comparison 48 (Suplasyn + NSAID) versus NSAID: 1 week post‐injection, Outcome 1 Pain after walking (0‐10 cm VAS).
Comparison 48 (Suplasyn + NSAID) versus NSAID: 1 week post‐injection, Outcome 2 WOMAC pain (0‐10 cm VAS).
Comparison 48 (Suplasyn + NSAID) versus NSAID: 1 week post‐injection, Outcome 3 Pain at rest (0‐10 cm VAS).
Comparison 48 (Suplasyn + NSAID) versus NSAID: 1 week post‐injection, Outcome 4 WOMAC function (0‐10 cm VAS).
Comparison 48 (Suplasyn + NSAID) versus NSAID: 1 week post‐injection, Outcome 5 Walk time (sec).
Comparison 48 (Suplasyn + NSAID) versus NSAID: 1 week post‐injection, Outcome 6 Safety: total withdrawals overall.
Comparison 49 Zeel compositum versus Hyalart (end of treatment (5 weeks)), Outcome 1 Pain during movement (0‐100 mm VAS ).
Comparison 49 Zeel compositum versus Hyalart (end of treatment (5 weeks)), Outcome 2 Pain during the night (0‐100 mm VAS).
Comparison 49 Zeel compositum versus Hyalart (end of treatment (5 weeks)), Outcome 3 Patient global: number of patients with noticeable improvements in symptoms.
Comparison 49 Zeel compositum versus Hyalart (end of treatment (5 weeks)), Outcome 4 Patient assessment of improvement (0‐100 mm VAS).
Comparison 49 Zeel compositum versus Hyalart (end of treatment (5 weeks)), Outcome 5 Patient assessment of tolerance (0‐100 mm VAS).
Comparison 49 Zeel compositum versus Hyalart (end of treatment (5 weeks)), Outcome 6 Safety: number of patients with side effects.
Comparison 49 Zeel compositum versus Hyalart (end of treatment (5 weeks)), Outcome 7 Safety: number of patients withdrawn due to lack of efficacy.
Comparison 50 HA/hylan versus placebo, Outcome 1 Pain on weight bearing (0‐100 mm VAS).
Comparison 50 HA/hylan versus placebo, Outcome 2 Pain at rest (0‐100 mm VAS).
Comparison 50 HA/hylan versus placebo, Outcome 3 WOMAC pain.
Comparison 50 HA/hylan versus placebo, Outcome 4 WOMAC physical function.
Comparison 50 HA/hylan versus placebo, Outcome 5 Lequesne Index (0‐24).
Comparison 50 HA/hylan versus placebo, Outcome 6 Patient global assessment (number of patients improved).
Comparison 50 HA/hylan versus placebo, Outcome 7 Flexion (degrees).
Comparison 50 HA/hylan versus placebo, Outcome 8 Safety: total withdrawals overall.
Comparison 50 HA/hylan versus placebo, Outcome 9 Safety: number of patients with local adverse reaction and study drug discontinued.
Comparison 50 HA/hylan versus placebo, Outcome 10 Safety: number of patients with local adverse reaction but study drug continued.
Comparison 50 HA/hylan versus placebo, Outcome 11 Safety: number of patients discontinued due to adverse events.
Comparison 50 HA/hylan versus placebo, Outcome 12 Safety: withdrawals due to lack of efficacy.
Comparison 50 HA/hylan versus placebo, Outcome 13 Safety: number of adverse events for injection site pain.
Comparison 50 HA/hylan versus placebo, Outcome 14 Safety: number of adverse events local skin rash.
Comparison 50 HA/hylan versus placebo, Outcome 15 Safety: number of patients with gastrointestinal complaints.
Comparison 50 HA/hylan versus placebo, Outcome 16 Safety: number of patients with treatment related adverse events.
Comparison 50 HA/hylan versus placebo, Outcome 17 Safety: number of patients with possible study medication related events.
Comparison 50 HA/hylan versus placebo, Outcome 18 Safety: number of serious adverse events.
Comparison 50 HA/hylan versus placebo, Outcome 19 Safety: number of adverse events probably or possibly related to treatment.
Comparison 50 HA/hylan versus placebo, Outcome 20 Safety: number of patients reporting adverse events.
Comparison 51 HA/hylan versus NSAID, Outcome 1 Pain after walking (0‐100 mm VAS).
Comparison 51 HA/hylan versus NSAID, Outcome 2 Patient general satisfaction wtih treatment (excellent or good vs satisfactory or bad).
Comparison 51 HA/hylan versus NSAID, Outcome 3 Safety: total withdrawals overall.
Comparison 51 HA/hylan versus NSAID, Outcome 4 Safety: number of withdrawals due to inefficacy.
Comparison 52 HA/hylan versus Methylprednisolone acetate, Outcome 1 Function: range of motion (active flexion in degrees).
Comparison 53 HA versus HA, Outcome 1 Pain in movement (number of patients improved).
Comparison 53 HA versus HA, Outcome 2 Pressure pain (number of patients improved).
Comparison 53 HA versus HA, Outcome 3 Lequesne Index (0‐24).
Comparison 53 HA versus HA, Outcome 4 Patient global assessment.
Source: PubMed