Multiple collagenase injections effective, safe for treating ‘frozen shoulder’

Patients regained shoulder function and motion, and experienced pain relief through one-year follow-up.

CHICAGO — A short period of collagenase injections can restore shoulder motion and function and provide long-term pain relief in adhesive capsulitis patients, according to investigators at Stony Brook University Hospital and Medical Center in Stony Brook, N.Y.

Sixty patients enrolled in the randomized, placebo-controlled, double-blind, dose response investigation after suffering from adhesive capsulitis (frozen shoulder) for a mean of 17 months.

Researchers injected 15 patients with placebo and 45 patients with either a low-, medium- or high-dose injection of collagenase. However, they found a single injection at any dose was not sufficient. Twenty-three patients required an additional high-dose injection and another 20 patients required two additional injections.

“Open-label repeat injections showed clear improvement,” Marie A. Badalamente, PhD, of Stony Brook University, said at the American Academy of Orthopaedic Surgeons 73rd Annual Meeting.

Badalamente conducted the study with colleague Edward Wang, MD. “Improvements were not short-lived and there were no recurrences. This technique had a high degree of patient satisfaction and we continue to study it based on the FDA regulatory process,” she said.

Injection method

The study included 47 men and 13 women with a mean age of 52 years. Researchers injected placebo patients with 0.9% saline/2 mM CaCl₂, Badalamente said. Patients injected with collagenase were evenly subdivided by dose: 16 received 0.145 mg, 15 received 0.29 mg and 14 received 0.58 mg.

The researchers first injected patients with lidocaine anesthesia. They then used a Sprotte 22-gauge noncutting needle to administer placebo or collagenase via extra-articular injections in the anterior shoulder capsule.

“In passive external rotation, the biceps tendon in the bicipital groove was palpated, as well as the coracoid,” Badalamente said. “The injection site was midway between these two landmarks.” The researchers verified the injection method on cadavers prior to treating study patients, she noted.

ASES scores

Using the American Society for Shoulder and Elbow Surgeons’ (ASES) Evaluation Form, researchers measured the patients’ ranges of motion, pain scores and function scores at follow-up days 1, 2, 4, 7, 14 and 30, Badalamente said.

At one month following the first injection, the researchers found that collagenase-treated patients significantly improved in four of eight ASES outcome scores compared to placebo patients (P<.05). High-dose (0.58 mg) collagenase-treated patients showing the most improvement, as follows:

Active elevation: 124.5 for placebo patients vs. 139.7 for high-dose collagenase patients;
Passive external rotation: 44.5 for placebo patients vs. 59.5 for high-dose collagenase patients; and
Function score: 43 for placebo patients vs. 49.8 for high-dose patients.

However, patients in the medium-dose (0.29 mg) collagenase group showed better improvement in active external rotation. These patients had a mean score of 52.6 compared to 42.4 for placebo patients, 42.3 for low-dose (0.145 mg) collagenase patients and to 48.6 for high-dose collagenase patients.

Second and third injections

Researchers offered patients the option of additional high-dose injections if they did not show a significant improvement in shoulder motion, pain and function scores. They limited additional injections to a maximum of four within a five- to six-week interval, Badalamente said. Most patients did opt for additional injections due to insufficient improvement, but three patients received an additional injection to treat their other shoulder.

Badalamente and her colleagues measured the ASES scores of 46 patients with unaffected contralateral shoulders to determine “normality” before frozen shoulder developed. They the compared these measures with the affected shoulder after treatment.

Beginning at postinjection day 1, patients treated with additional high-dose injections dramatically improved in shoulder motion, pain and function (P<.05). “The parameters approached normal at one month, based on the means of the unaffected contralateral shoulders,” Badalamente said.

Patients maintained improvements at long-term follow-up of a mean 1.8 years.

Some patients experienced adverse events, including infection area tenderness, biceps ecchymosis and mild edema, all of which resolved within seven to 14 days, Badalamente said.

No adverse immune effects were found using specific anticoagulated IgA and IgG assays, she noted.

For more information:
Badalamente M, Wang E. Enzymatic capsulotomy for adhesive capsulitis: Collagenase injection therapy. #433. Presented at the American Academy of Orthopaedic Surgeons 73rd Annual Meeting. March 22-26, 2006. Chicago.