<b>PURPOSE: </b>To compare the effectiveness of intraarticular (IA) multiple and single platelet-rich plasma (PRP) injections as well as hyaluronic acid (HA) injections in different stages of osteoarthritis (OA) of the knee.<b>METHODS: </b>A total of 162 patients with different stages of knee OA were randomly divided into four groups receiving 3 IA doses of PRP, one dose of PRP, one dose of HA or a saline injection (control). Then, each group was subdivided into two groups: early OA (Kellgren-Lawrence grade 0 with cartilage degeneration or grade I-III) and advanced OA (Kellgren-Lawrence grade IV). The patients were evaluated before the injection and at the 6-month follow-ups using the EuroQol visual analogue scale (EQ-VAS) and International Knee Documentation Committee (IKDC) subjective scores. Adverse events and patient satisfaction were recorded.<b>RESULTS: </b>There was a statistically significant improvement in the IKDC and EQ-VAS scores in all the treatment groups compared with the control group. The knee scores of patients treated with three PRP injections were significantly better than those patients of the other groups. There was no significant difference in the scores of patients injected with one dose of PRP or HA. In the early OA subgroups, significantly better clinical results were achieved in the patients treated with three PRP injections, but there was no significant difference in the clinical results of patients with advanced OA among the treatment groups.<b>CONCLUSION: </b>The clinical results of this study suggest IA PRP and HA treatment for all stages of knee OA. For patients with early OA, multiple (3) PRP injections are useful in achieving better clinical results. For patients with advanced OA, multiple injections do not significantly improve the results of patients in any group.<b>LEVEL OF EVIDENCE: </b>I.
BACKGROUND: The effectiveness of diclofenac versus paracetamol in primary care patients with pain caused by knee osteoarthritis is unclear.
AIM: To assess the effectiveness of diclofenac compared with paracetamol over a period of 2, 4, and 12 weeks in patients with knee osteoarthritis.
DESIGN AND SETTING: Randomised controlled trial in general practice.
METHOD: There were 104 patients included in the study, they were aged ≥45 years consulting their GP with knee pain caused by knee osteoarthritis. Patients were randomly allocated to diclofenac (n = 52) or paracetamol (n = 52) for at least 2 weeks. Primary outcomes were daily knee pain severity, and knee pain and function measured with the Knee Injury and Osteoarthritis Outcome Score (KOOS).
RESULTS: Over a period of 2- and 4-weeks follow-up, no significant difference in daily knee pain was found between the patient groups: estimated differences of 0.5 (95% CI = -0.2 to 1.3) and -0.2 (95% CI = -1.0 to 0.7), respectively. Over the 12-weeks follow-up, no significant differences were found between both groups for KOOS pain: estimated difference of -2.8 (95% CI = -10.7 to 5.1) and KOOS function of -2.7 (-10.6 to 5.0).
CONCLUSION: Over a period of 2- and 4-weeks follow-up no significant difference in daily measured knee pain severity was found between primary care patients with knee osteoarthritis taking paracetamol or diclofenac. Also, over a period of 12-weeks follow-up no significant differences were found regarding KOOS pain and KOOS function between both groups. Patients more frequently reported minor adverse events after taking diclofenac (64%) than paracetamol (46%).
The main goal of our study was to examine the effectiveness and safety of Fermathron plus, a specific brand of hyaluronic acid (HA), in patients with mild to moderate knee osteoarthritis. In a randomized, controlled, double-blind trial, 196 patients with symptomatic knee osteoarthritis (mean age ± SD, 59.4 ± 9.9 years, Kellgren-Lawrence grade 1-3) were given either 3 weekly intra-articular injections of HA or saline (placebo). Although pain and functional scores (WOMAC scale) improved significantly from baseline up to 6 months, HA was not superior to placebo at any follow-up (VAS pain 50 m walking from 56.4 to 38.1, P < .001, and 58.2 to 39.6, P < .001, respectively). No subgroup analysis resulted in superior outcomes. No serious adverse events were noticed.
IMPORTANCIA: La osteoartritis (OA) de rodilla es la forma más frecuente de artritis y una de las causas del dolor y la discapacidad. Los tratamientos no farmacológicos y farmacológicos combinados se recomiendan como el enfoque de tratamiento óptimo, pero no hay evidencia apoya la recomendación.
Objetivo: Evaluar los beneficios clínicos de una inyección de corticosteroides intraarticular dada antes de la terapia de ejercicio en pacientes con OA de la rodilla.
Diseño, lugar y participantes: Se realizó un ciego, ensayo clínico aleatorizado, controlado con placebo evaluando el beneficio de la inyección de corticosteroides intraarticular versus placebo inyección administrada antes de la terapia de ejercicio en una clínica ambulatoria OA del 1 de octubre de 2012 hasta el 2 de abril 2014. Los participantes tuvieron la confirmación radiográfica de OA clínica de la rodilla, los signos clínicos de la inflamación localizada en la rodilla, y dolor en la rodilla durante la marcha (puntuación> 4 en una escala de 0 a 10).
Intervenciones: Los participantes se asignaron al azar (1: 1) a una intra-articular de inyección de 1 ml de la rodilla con acetato de metilprednisolona (Depo-Medrol), 40 mg / mL, se disolvió en 4 ml de clorhidrato de lidocaína (10 mg / mL) (grupo de corticosteroides) o una inyección de solución salina isotónica 1 ml se mezcla con 4 ml de hidrocloruro de lidocaína (10 mg / mL) (grupo placebo). Dos semanas después de las inyecciones, todos los participantes comenzaron 12 semanas de programa de ejercicio supervisado.
PRINCIPALES RESULTADOS Y MEDIDAS: El resultado primario fue el cambio en la subescala de dolor de la osteoartritis de rodilla y lesión de resultados Score (KOOS) cuestionario (rango, 0-100; las puntuaciones más altas indican una mayor mejoría) en la semana 14. Los resultados secundarios incluyeron las subescalas KOOS restantes y medidas objetivas de la función física y la inflamación. Los resultados se midieron al inicio del estudio, la semana 2 (inicio del ejercicio), la semana 14 (parada de ejercicio), y la semana 26 (seguimiento).
RESULTADOS: Cien pacientes fueron asignados al azar al grupo de corticosteroides (n = 50) o el grupo de placebo (n = 50); 45 y 44 pacientes, respectivamente, completaron el ensayo. Las medias (SE) los cambios en la puntuación de la subescala KOOS Dolor en la semana 14 fueron de 13,6 (1,8) y 14,8 (1,8) puntos en los grupos de corticosteroides y placebo, respectivamente, lo que corresponde a una diferencia media estadísticamente insignificante de 1,2 puntos (IC del 95%, -3.8 a la 6.2; P = 0,64). No se encontraron diferencias entre los grupos estadísticamente significativas en ninguno de los resultados secundarios en cualquier punto del tiempo.
Conclusiones y relevancia: ningún resultado beneficios adicionales a partir de la adición de una inyección intra-articular de 40 mg de corticosteroides antes del ejercicio en pacientes con artrosis dolorosa de la rodilla. Se necesitan más investigaciones para establecer las combinaciones óptimas y potencialmente sinérgicos de los tratamientos conservadores.
Prueba de registro: Identificador clinicaltrialsregister.eu: 2012-002607-18; clinicaltrials.gov Identificador: NCT01945749.
BACKGROUND: Osteoarthritis (OA) is a common disease that will affect almost half the population at some point in their lives through pain and decreased functional capacity. New nonoperative options are being proposed to treat earlier stages of joint degeneration to provide symptomatic relief and delay surgical intervention.
PURPOSE: To evaluate the benefit provided by platelet-rich plasma (PRP) injections to treat knee joint degeneration in comparison with hyaluronic acid (HA), the most common injective treatment currently adopted for this condition.
STUDY DESIGN: Randomized controlled trial; Level of evidence, 1.
METHODS: A total of 443 patients were screened, and 192 of them were enrolled in the study according to the following inclusion criteria: (1) unilateral symptomatic knee with history of chronic pain (at least 4 months) or swelling and (2) imaging findings of degenerative changes (Kellgren-Lawrence score of 0-3 at radiographs or MRI evidence of degenerative chondropathy). Patients underwent 3 weekly intra-articular injections of either PRP or HA. Patients were prospectively evaluated at baseline and then at 2, 6, and 12 months of follow-up using the International Knee Documentation Committee (IKDC) subjective score (main outcome), Knee injury and Osteoarthritis Outcome Score, EuroQol visual analog scale, and Tegner score. Range of motion, transpatellar circumference, patient satisfaction, and adverse events were also recorded.
RESULTS: Two patients reported severe pain and swelling after HA injections, while no major adverse events were noted in the PRP group. However, PRP presented overall significantly more postinjection swelling and pain. Both treatments proved to be effective in improving knee functional status and reducing symptoms: the IKDC score in the PRP group rose from 52.4 ± 14.1 to 66.2 ± 16.7 at 12 months (P < .0005), and in the HA group it rose from 49.6 ± 13.0 to 64.2 ± 18.0 at 12 months (P < .0005). A similar trend was observed for all the clinical scores used. The comparative analysis of the 2 treatments showed no significant intergroup difference at any follow-up evaluation in any of the clinical scores adopted.
CONCLUSION: PRP does not provide a superior clinical improvement with respect to HA, and therefore it should not be preferred to viscosupplementation as injective treatment of patients affected by knee cartilage degeneration and OA.
BACKGROUND: Celecoxib is an effective treatment for osteoarthritis (OA). However, information on its efficacy and safety profile in different racial/ethnic groups is limited. Noticeable differences among racial groups are found in other disease states, but a thorough investigation of OA is lacking. The objective of this study was to determine if celecoxib 200 mg once daily is as effective as naproxen 500 mg twice daily in the treatment of OA of the knee in Hispanic patients.
METHODS: Hispanic patients aged ≥45 years with knee OA were randomized to receive celecoxib 200 mg once daily, naproxen 500 mg twice daily, or placebo for 6 weeks. The primary efficacy variable was the change in Patient's Assessment of Arthritis Pain at 6 weeks compared with baseline. Secondary variables were change in Patient's and Physician's Global Assessments of Arthritis from baseline to week 6/early termination, change in Western Ontario and McMaster Universities OA Index (WOMAC) from baseline to week 6/early termination, change in American Pain Society pain score, Pain Satisfaction Scale, Patient Health Questionnaire (PHQ-9), and measurements of upper gastrointestinal tolerability.
RESULTS: In total, 239 patients completed the trial (96 celecoxib, 96 naproxen, 47 placebo). Celecoxib was as effective as naproxen in reducing OA pain (least squares mean change from baseline [standard error] -39.7 [2.7] for celecoxib and -36.9 [2.6] for naproxen). Patient's and Physician's Global Assessments of Arthritis, WOMAC scores, upper gastrointestinal tolerability, Pain Satisfaction Scale, and PHQ-9 showed no statistically significant differences between the celecoxib and naproxen groups. The incidence of adverse events and treatment-related adverse events were similar among the treatment groups.
CONCLUSION: Celecoxib 200 mg once daily was as effective as naproxen 500 mg twice daily in the treatment of signs and symptoms of knee OA in Hispanic patients. Celecoxib was shown to be safe and well tolerated in this patient population.
<b>PURPOSE: </b>To assess the efficacy and safety of one and two intra-articular (IA) injections of the new viscosupplement, hylastan, compared with a single IA corticosteroid injection for pain due to knee osteoarthritis (OA). Hylastan is a high-molecular-weight hyaluronan derivative prepared from bacterial fermented sodium hyaluronate that was developed to remain in the joint for longer than most other viscosupplements.<b>METHODS: </b>This 6-month, double-blind, randomized, parallel group, multicenter trial enrolled patients aged ≥40 years who met American College of Rheumatology criteria for knee OA and had continued pain despite conservative treatment. Patients were randomized 1:1:1 to one of three arms: 2 × 4 mL hylastan (n = 129; arthrocentesis then IA hylastan Day 0, same treatment Week 2); 1 × 4 mL hylastan (n = 130; arthrocentesis then IA hylastan Day 0, arthrocentesis only Week 2); steroid (n = 132; arthrocentesis then IA methylprednisolone acetate 40 mg Day 0, arthrocentesis only Week 2). Participants and evaluators were blinded to treatment. The primary clinical outcome measure was change from baseline in WOMAC A pain score over all postbaseline visits to Week 26.<b>RESULTS: </b>Statistically significant pain reduction was observed in all three arms, with similar mean (95 % CI) changes in WOMAC A: 2 × 4 mL hylastan -0.9 (-1.0, -0.7); 1 × 4 mL hylastan -0.8 (-0.9, -0.7); steroid -0.9 (-1.0, -0.8); all P < 0.0001 versus baseline. Changes in secondary outcomes (OMERACT-OARSI and WOMAC A responder rates, patient/clinical observer global assessments, and WOMAC A1 walking pain) were similar in all three arms. Target knee adverse events were comparable for all treatments.<b>CONCLUSIONS: </b>Both IA hylastan injection regimens were effective in relieving pain with an acceptable safety profile. IA hylastan did not show a difference versus IA corticosteroid; therefore, the hypothesis of superior pain relief was not met. Further research is needed to compare the efficacy and safety of hylastan with other viscosupplements.
Abstract OBJECTIVE: NSAIDs, such as diclofenac, are the most commonly used medications to treat osteoarthritis (OA), but they are associated with dose-related adverse events (AEs). Low-dose submicron diclofenac was developed using a new, proprietary dry milling process that creates submicron drug particles (SoluMatrix Fine Particle Technology * ), enabling effective treatment at lower doses than other commercially available diclofenac drug products. This phase 3 study evaluated the efficacy and safety of low-dose submicron diclofenac 35 mg three times daily (tid) and twice daily (bid) in patients with OA pain. RESEARCH DESIGN AND METHODS: This double-blind study enrolled patients >=40 years of age with clinically and radiographically confirmed (Kellgren-Lawrence grade II-III) hip or knee OA. Eligible patients were chronic NSAID and/or acetaminophen (APAP) users with baseline Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC) pain subscale scores >=40 mm by visual analog scale and an OA flare (>=15 mm increase in WOMAC pain subscale score following discontinuation of NSAIDs/APAP at screening). Patients were randomized to submicron diclofenac 35 mg tid, submicron diclofenac 35 mg bid, or placebo for 12 weeks. ClinicalTrials.gov identifier: NCT01461369. MAIN OUTCOME MEASURES: Efficacy parameters included mean change from baseline in WOMAC pain subscale score at week 12 (primary efficacy parameter) and in average total WOMAC score over 12 weeks. RESULTS: Submicron diclofenac 35 mg tid significantly improved WOMAC pain subscale scores from baseline at 12 weeks (-44.1; p = 0.0024) compared with placebo (-32.5). Submicron diclofenac 35 mg bid provided numerical improvement in pain at week 12 that did not reach statistical significance (-39.0; p = 0.0795) compared with placebo. Submicron diclofenac 35 mg tid (-35.9; p = 0.0002) and 35 mg bid (-30.3; p = 0.0363) improved the average total WOMAC score in treated patients over 12 weeks compared with placebo (-23.2). The most frequent AEs in the submicron diclofenac-treated groups were diarrhea, headache, nausea, and constipation. The inclusion of patients with a documented requirement for analgesic therapy (OA 'flare') at baseline and the high rates of rescue medication usage in the placebo group may have impacted the study outcome for the submicron diclofenac treatment groups. CONCLUSIONS: Low-dose submicron diclofenac is an effective therapeutic option for the treatment of OA pain.
<b>OBJECTIVE: </b>NASHA hyaluronic acid is administered as a single intra-articular injection to treat the symptoms of osteoarthritis (OA). In a previous trial, post-hoc analysis indicated that NASHA provides significantly greater pain relief than saline in patients with OA confined to the study knee. We aimed to evaluate the safety and efficacy of NASHA in patients with unilateral knee OA.<b>RESEARCH DESIGN AND METHODS: </b>This was a randomized, double-blind, saline-controlled trial. All patients had knee OA confirmed by American College of Rheumatology criteria and a WOMAC pain score of 7-17 in the study knee, but no pain in the previous 3 months in the non-study knee. Treatment comprised a single intra-articular injection of NASHA or saline control. The follow-up period was 6 weeks.<b>Clinical Trial Registration: </b>ClinicalTrials.gov NCT01806207.<b>MAIN OUTCOME MEASURES: </b>The primary efficacy endpoint was the responder rate, defined as the percentage of patients with ≥40% improvement from baseline in WOMAC pain score and an absolute improvement of ≥5 points.<b>RESULTS: </b>A total of 218 patients received study treatment (NASHA: 108, saline: 110). In the main intention-to-treat (ITT) analysis, no statistically significant difference in responder rate was found between the two groups at 6 weeks (NASHA: 30.6%; saline: 26.4%). A post-hoc subgroup analysis of patients without clinical effusion in the study knee at baseline showed a significantly higher 6 week responder rate with NASHA than with saline: 40.6% versus 19.7% (p = 0.0084). A total of 68 adverse events were reported among 44 patients in the NASHA group, compared with 69 adverse events among 44 patients in the saline group. The main weakness of the study was the short, 6 week follow-up duration. In addition, image guidance was not used to ensure injection as intended into the intra-articular space.<b>CONCLUSIONS: </b>Single-injection NASHA was well tolerated and, although there was no significant benefit versus saline control in the primary analysis, post-hoc analysis showed a statistically significant improvement in pain relief at 6 weeks among patients without clinical effusion at baseline.
<b>OBJECTIVE: </b>To compare NASHA hyaluronic acid gel as single-injection intra-articular (IA) treatment for knee osteoarthritis (OA) against methylprednisolone acetate (MPA).<b>DESIGN: </b>This was a prospective, multi-centre, randomized, active-controlled, double-blind, non-inferiority clinical trial. A unique, open-label extension phase (OLE) was undertaken to answer further important clinical questions. Subjects with painful unilateral knee OA were treated and followed for 26 weeks (blinded phase). All patients attending the clinic at 26 weeks were offered NASHA treatment, with a subsequent 26-week follow-up period (extension phase). The primary objective was to show non-inferiority of NASHA vs MPA in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain responder rate (percentage of patients with ≥40% improvement from baseline in WOMAC pain score and an absolute improvement of ≥5 points) at 12 weeks.<b>RESULTS: </b>In total, 442 participants were enrolled. The primary objective was met, with NASHA producing a non-inferior response rate vs MPA at 12 weeks (NASHA: 44.6%; MPA: 46.2%; difference [95% CI]: 1.6% [-11.2%; +7.9%]). Effect size for WOMAC pain, physical function and stiffness scores favoured NASHA over MPA from 12 to 26 weeks. In response to NASHA treatment at 26 weeks, sustained improvements were seen in WOMAC outcomes irrespective of initial treatment. No serious device-related adverse events (AEs) were reported.<b>CONCLUSIONS: </b>This study shows that single-injection NASHA was well tolerated and non-inferior to MPA at 12 weeks. The benefit of NASHA was maintained to 26 weeks while that of MPA declined. An injection of NASHA at 26 weeks conferred long-term improvements without increased sensitivity or risk of complications. STUDY IDENTIFIER: NCT01209364 (www.clinicaltrials.gov).
To compare the effectiveness of intraarticular (IA) multiple and single platelet-rich plasma (PRP) injections as well as hyaluronic acid (HA) injections in different stages of osteoarthritis (OA) of the knee.
METHODS:
A total of 162 patients with different stages of knee OA were randomly divided into four groups receiving 3 IA doses of PRP, one dose of PRP, one dose of HA or a saline injection (control). Then, each group was subdivided into two groups: early OA (Kellgren-Lawrence grade 0 with cartilage degeneration or grade I-III) and advanced OA (Kellgren-Lawrence grade IV). The patients were evaluated before the injection and at the 6-month follow-ups using the EuroQol visual analogue scale (EQ-VAS) and International Knee Documentation Committee (IKDC) subjective scores. Adverse events and patient satisfaction were recorded.
RESULTS:
There was a statistically significant improvement in the IKDC and EQ-VAS scores in all the treatment groups compared with the control group. The knee scores of patients treated with three PRP injections were significantly better than those patients of the other groups. There was no significant difference in the scores of patients injected with one dose of PRP or HA. In the early OA subgroups, significantly better clinical results were achieved in the patients treated with three PRP injections, but there was no significant difference in the clinical results of patients with advanced OA among the treatment groups.
CONCLUSION:
The clinical results of this study suggest IA PRP and HA treatment for all stages of knee OA. For patients with early OA, multiple (3) PRP injections are useful in achieving better clinical results. For patients with advanced OA, multiple injections do not significantly improve the results of patients in any group.
LEVEL OF EVIDENCE:
I.
Diseño del estudio»Ensayo controlado aleatorizado (ECA)
