Pharmacological prevention of arthrofibrosis: a systematic review.

Background and aims: Arthrofibrosis is a complication of intra-articular knee surgery which is caused by intra-articular fibrosis. To date, several preventive therapies for arthrofibrosis have been reported. This systematic review aims to summarize current knowledge about pharmacological arthrofibrosis prevention.

Methods: A systematic literature search was conducted in Medline, Web of Science, and Cochrane library using the search term 'Arthrofibrosis AND prevention'. Subsequently, articles reporting the effects of a preventive pharmacological intervention against arthrofibrosis were included in this review.

Results: 16 studies investigated the pharmacological prevention of arthrofibrosis of which 13 were conducted in animal models. Several drugs improved the range of motion (ROM) in animal models. Bevacizumab (ROM +39.4 degrees), nonsteroidal anti-inflammatory drugs (ROM +18.0-31.2 degrees), and rosiglitazone (ROM +19.5 degrees) significantly increased the ROM. Artesunate, mitomycin c, bevacizumab, hyaloglide, and botulinum toxin A significantly reduced adhesion scores. None of the drugs tested in humans improved the functional outcomes after joint arthroplasty. Methodological differences limited the ability to compare outcomes and, due to poor reporting of methodology, many studies had an unclear risk of bias.

Conclusion: This review identified several drugs as potential candidates for arthrofibrosis prevention. These drugs modulate inflammation or alter the activity of fibroblasts. Most studies are conducted in experimental animal models and none of these results are currently translated into a clinical application. Moreover, the methodology and route of administration varied between studies. Nor were dose dependency studies conducted. Future studies should adopt a standardized approach to determine the effects of preventive pharmacological interventions on arthrofibrosis.