<p><em>Clostridium histolyticum</em> (AA4500) for the Treatment of Adhesive Capsulitis of the Shoulder: A Randomised Double-Blind, Placebo-Controlled Study for the Safety and Efficacy of Collagenase – Single Site Report</p>

Abstract

Background/Hypothesis: Adhesive capsulitis of the shoulder results in pain and restricted movement of the glenohumeral joint. Hypothesis: There would be a difference in active range of movement in the affected shoulder of patients with adhesive capsulitis after receiving a series of injections of collagenase Clostridium histolyticum (CCH) compared to placebo. Methods: This study reports the results from a single site that was part of a 321-participant, multicenter, double-blind, prospective parallel-group, randomized controlled clinical trial. Inclusion criteria: over 18 years of age, unilateral idiopathic adhesive capsulitis for >3 months, but <12 months. Exclusion criteria: recent physical therapy, injections, subacromial impingement, calcific tendonitis or glenohumeral joint arthritis in the affected shoulder. Subjects were randomized 3:1 to receive CCH 0.58 mg or placebo under ultrasound guidance. Injections were on days 1, 22, and 43. The primary outcome measure was a functional assessment of active range of movement. Results: Overall, 37 patients were screened, 26 subjects were excluded, and 11 subjects were randomly assigned to the treatment group (n=9) or the control group (n=2). Both control and treatment groups showed improvement in ROM between baseline and day 95. In the treatment group, AROM improved from the baseline of 272.89°(SD 86.25) to 462.11°(SD 96.89) and the control group from 246.00°(SD 5.66) to 451.50°(SD 50.20) at day 95 with no statistical difference between groups p=0.78. Site data were in line with the whole study findings. Treatment-related adverse events at the injection site, including haematoma (bruising) and localised pain and swelling, were common. Conclusion: Although the participants showed improvement in function, statistical significance was neither reached in the site nor the overall study cohort. Given the adverse events and the potential risks of the procedure, we would not recommend this drug for the treatment of adhesive capsulitis of the shoulder. Level of Evidence: 2, cohort from one site of RCT.

Human bone marrow mesenchymal stem cell-derived extracellular vesicles inhibit shoulder stiffness via let-7a/Tgfbr1 axis

“…Some animal studies have performed collagenase injection to treat SS, which resulted in good outcomes [ [51] , [52] , [53] ]. However, as collagen is an indispensable part of the extracellular matrix, it is not clear whether collagenase could be utilized in clinical practice or not [ 54 ]. Alternatively, we proved the possibility of collagen secretion inhibition by BMSC-EVs, of which the effect relied on TGF-β/Smad signaling.…”

Frozen shoulder

“…CCH is typically given in a series of 3 injections over 6 weeks. A randomized study showed improvement in subjective function with CCH but no notable increase in ROM compared with placebo 151 . Another study found a greater improvement in ROM at 3 months with CCH than with exercise therapy alone 143 .…”

The Versatility of Collagen in Pharmacology: Targeting Collagen, Targeting with Collagen

“…While CCH has shown relative safety and efficacy, it can trigger the production of neutralizing antibodies in patients [ 47 ]. Additionally, AA4500 has proven ineffective in treating other fibrotic conditions, such as adhesive capsulitis of the shoulder [ 48 ]. Potential future applications abound.…”