Single intra-articular injection of lightly cross-linked hyaluronic acid reduces knee pain in symptomatic knee osteoarthritis: a multicenter, double-blind, randomized, placebo-controlled trial

Abstract

Purpose

The primary objective was to demonstrate the safety and effectiveness of Monovisc™ in the relief of joint pain in patients with idiopathic knee OA compared to saline injection. It was hypothesized that patient success, defined as ≥ 50% improvement from baseline and ≥ 20 mm absolute improvement from baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) visual analog scale (VAS) pain score, would be greater in the Monovisc™ group compared to the Saline control group.

Methods

In this multicenter, double-blind, randomized, placebo-controlled trial, patients with idiopathic, symptomatic, knee OA were randomized to either 4 ml single injection of Monovisc™ or 4 ml injection of 0.9% saline. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was used to assess patient outcomes at 2, 4, 8, 12, 20, and 26 weeks post-injection. The primary effectiveness endpoint was a 50% improvement and ≥ 20 mm improvement from baseline in the WOMAC pain through 26 weeks. Secondary outcome measures included a ≥ 20 mm improvement from baseline on the WOMAC physical function, patient global assessment, evaluator global assessment, and knee range of motion.

Results

369 patients (154 male, 215 female) were randomized to either Monovisc™ or saline. The Monovisc™ group had a significantly greater rate of patient success (e.g. ≥ 50% improvement and ≥ 20 mm absolute improvement from baseline in the WOMAC pain through Week 26) compared to saline (p = 0.043).

Conclusions

Monovisc™, a single-injection intra-articular HA device, is a safe and effective treatment for providing a clinically meaningful reduction in knee pain within 2 weeks. The results of this study support the use of a single injection of hyaluronic acid (Monovisc™) for patients with symptomatic knee OA in patients older than 45 years, as a safe and effective alternative for patients who may want an alternative treatment modality or may not be candidates for partial or total knee replacement.

Level of evidence

I, multicenter, double-blind, randomized, placebo-controlled trial.

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Fig. 1

Abbreviations

OA:

Osteoarthritis

WOMAC:

Western Ontario and McMaster Universities Osteoarthritis Index

VAS:

Visual analog scale

US:

United States

NSAIDS:

Non-steroidal anti-inflammatory medications

HA:

Hyaluronic acid

USD:

United States dollar

AAOS:

American Academy of Orthopaedics

IRB:

Institutional Review Board

GCP:

Good clinical practice

ICH:

International Conference on Harmonization

BMI:

Body mass index

K–L:

Kellgren–Lawrence

MedDRA:

Medical Dictionary for Regulatory Activities

ITT:

Intent-to-treat

PP:

Per protocol

GEE:

Generalized estimating equations

MCID:

Minimum clinically important differences

ROM:

Range of motion

ACR:

American College of Rheumatology

OARSI:

Osteoarthritis Research Society International

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Acknowledgements

The authors would like to personally thank all the principal investigators and study coordinators for their help with subject recruitment and data collection. Special thanks go to Dr. Baraf, Dr. Covall, Dr. Kivitz, and Dr. Neustadt for their assistance in the completion of this manuscript and to Gary Stevens for his assistance with the data analysis.

Funding

This manuscript is based upon clinical trial results from a study sponsored by Anika Therapeutics.

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Drs. Stephanie Petterson and Kevin Plancher were responsible for all aspects of manuscript development and submission.

Corresponding author

Correspondence to Kevin D. Plancher.

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Grants or other financial support were received from Anika Therapeutics.

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Ethics committee approvals were obtained.

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Petterson, S.C., Plancher, K.D. Single intra-articular injection of lightly cross-linked hyaluronic acid reduces knee pain in symptomatic knee osteoarthritis: a multicenter, double-blind, randomized, placebo-controlled trial. Knee Surg Sports Traumatol Arthrosc 27, 1992–2002 (2019). https://doi.org/10.1007/s00167-018-5114-0

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Keywords

  • Monovisc™
  • Hyaluronic acid
  • Knee osteoarthritis
  • Intra-articular injection
  • Knee joint pain