Safety assessment of intra-articular 2.5% polyacrylamide hydrogel for treatment of knee osteoarthritis

Abstract

Purpose: There is a drought of available effective treatments of knee osteoarthritis (OA). However, new therapeutics and devices are being introduced, such as polyacrylamide gels. This study was conducted to retrospectively assess the safety and patient-reported treatment effect of intra-articular (IA) treatment of knee OA with a proprietary 2.5% cross-linked polyacrylamide gel (PAAG) in patients with knee OA. Methods: The safety evaluation encompassed a sample of patients who had been treated intra-articularly for knee OA symptoms with 2.5 % polyacrylamide hydrogel between March 2010 and February 2017. Safety assessments included the retrospective self-reported adverse events (AEs), medical record reviews, and a clinical examination of the treated knee. If any AEs or discomforts were reported, the patient was asked to describe its duration (“Days”, “Weeks”, “Months”) and severity (“Mild”, “Moderate”, “Severe”). For patients who since treatment had received knee arthroplasty surgery, the surgical records were reviewed for any description of abnormal observations. Patient-reported treatment effect vas measured via a transition questionnaire (Trans-Q), in which the patients scored the current knee status regarding ‘pain’, ‘function’, and ‘global’ in relation to pre-treatment status on a 15 points scale from −7 (‘Much worse’) to 7 (‘Much better’), with 0 being ‘No change’. The assessment was done at average 24 months after first treatment (range 4 to 87 months). Results: Of 126 patients invited to the safety assessment, 91 (72%) accepted the invitation. A majority of the study population (n = 66; 73%) reported no adverse events or discomfort after receiving single or multiple treatments with PAAG. Of the 25 patients who reported discomfort or adverse events, 15 reported a sensation of distention immediately after treatment. Most (n = 14 93%) described this as passing over a few days to weeks. 10 patients (67%) described this as mild. Two patients sought medical assistance (at the study clinic) after treatment for exacerbations of pain and inflammation, which were treated by oral analgesics and arthrocentesis resolving the symptoms within weeks. From the clinical examinations, the investigator found no signs of reduced knee ROM or other abnormalities than what is to be expected in a population of knee OA patients. 15 patients had received knee arthroplasty surgery since treatment of which 14 surgical reports were retrieved. In these we found no unexpected descriptions of abnormalities that could be associated with prior treatment with PAAG. In fact, none of the reports mention the presence of PAAG, unidentified foreign bodies or other findings not expected when inspecting an OA knee. The transition questionnaire describes an overall improvement on pain function and global improvement after treatment with PAAG corresponding to a score of 3 (“somewhat better”) for pain, 2 (“A little better”) for function, and 3 (“somewhat better”) for global. No adverse events causing hospitalizations (serious adverse events), intra-articular infections, or allergic reactions were reported. Conclusions: This retrospective safety assessment found no significant incidence of adverse events or serious adverse events related to the intra-articular treatment with a proprietary 2.5 % cross-linked polyacrylamide gel for the relief of knee osteoarthritis pain and disability. The safety of PAAG must be assessed further in a larger prospective study. However, these initial results suggest that the treatment may be regarded as safe.