BOSTON, Massachusetts—Botulinum toxin type A (BoNT/A), the active ingredient in Botox®, might soothe arthritic joints as well as smoothing the face, according to a proof-of-concept trial reported as a late-breaking poster at the American College of Rheumatology annual meeting.¹

A research team from the Minneapolis VA Medical Center, led by Jasvinder Singh, MBBS, MPH, found that a single injection of intra-articular (IA) BoNT/A into the shoulder joint reduced pain by at least 30% in patients with shoulder osteoarthritis (OA) for at least 28 days.

The study compared 21 patients randomized to BoNT/A (100 units plus lidocaine) and 22 patients randomized to placebo (saline plus lidocaine); the study extends the researchers' previous work in knee and ankle OA, according to Dr. Singh, staff physician at the Minneapolis VA Medical Center, assistant professor of medicine at the University of Minnesota, and visiting scientist and K-12 scholar at the Mayo Clinic School of Medicine. All patients had a 6-month history of shoulder pain refractory to IA corticosteroids and oral analgesics and were not candidates for shoulder arthroplasty.

At baseline, patients with moderate-to-severe OA pain scored >4.5 on a 0-10 numeric rating scale (NRS). At 28 days after the single injection, their daytime pain NRS was 5.11 with BoNT/A and 6.54 with placebo (P = .036); visual analog scale (VAS) pain was 4.12 versus 6.54 (P = .006).

"We were surprised to see, in such a small study, a difference that was statistically significant at day 28," Dr. Singh told Musculoskeletal Report.

Dr. Singh reported efficacy data for 43 joints in 38 patients (including five patients who had injections in both shoulders). Thirty-eight percent of joints injected with BoNT/A had >30% reduction in pain score compared with only 9% of joints injected with placebo. There was a trend toward a greater improvement in shoulder function in the BoNT/A group compared with the placebo group at 28 days. Durability of the pain relief is still under study, but Dr. Singh said that relief lasting 6 months had been observed in an uncontrolled, unblinded study of similar injections for knee and ankle OA pain.

Dr. Singh said that giving this type of injection is not technically difficult. "There are no arteries, veins, or muscles in the way. If you miss your target, the worst thing that happens is you hit bone, at which point the patient says, ‘Ouch!' and you redirect the needle."  The injection is generally done from a posterior approach, about 1 cm below the acromium angle, with the needle directed toward the midclavicle. "This is mainly for patient comfort. If you cannot see the needle, you have less anticipation anxiety."

Patients were assessed at baseline, 1-, 3-, and 6-months. The primary efficacy outcome measures of pain severity at 1 month were Visual Analog Scale (VAS, 0-10 cm), day pain on 0-10 NRS, Shoulder Pain and Disability Index (SPADI), and pain subscale score (0-100 mm, higher score = worse). Secondary outcomes included validated measures: SPADI Disability Index (0-100 mm scale; higher score = worse) and proportion of patients achieving >e;30% pain relief, an improvement that is considered to be clinically meaningful.

The proposed mechanism of action is that the injection of neurotoxin in the joint may decrease the release of neuropeptides required for nociceptor function, thus decreasing the pain sensation in the joint.

"IA neurotoxin injection for sustained analgesia is a promising new approach to persistent joint pain, which may act by inhibiting vesicle release of neuropeptides such as substance P and CGRP [calcitonin gene-related peptide] and disrupting nociceptor function to decrease pain," Dr. Singh said. "This study provides the initial ‘proof of concept' of effectiveness of botulinum toxin injection for relief of shoulder joint pain. A more sophisticated, larger, multicenter, randomized study is needed to assess efficacy, safety, mode of action, optimal dose and frequency of this novel treatment option."

Outcomes at Day 28 Postshoulder Joint Injection

IA-Botulinum toxin group (n = 21) mean or proportion (standard deviation) IA-Placebo group (n = 22) mean or proportion (standard deviation) Difference between groups (95% confidence interval) P value Primary Outcomes VAS Pain (0-10 cm) 4.12 (2.71) 6.54 (2.43) -2.43 (-4.12, -0.73) 0.006 Daytime Pain (0-10 NRS) 5.11 (2.6) 6.74 (2.17) -1.63 (-3.15, -0.11) 0.036 SPADI Pain Score (0-100) 49.67 (18.4) 65.79 (18.39) -16.12 (-27.68, -4.57) 0.007 Secondary Outcomes SPADI Disability Score (0-100) 66.77 (19) 78.26 (17.9) -11.49 (-23.12, 0.14) 0.053 Proportion with >e;30% decrease in SPADI pain score 38.1% (10.6%) 9.1% (6.1%) -29% (-3%, -58%) 0.05 Proportion with >e;30% decrease in daytime pain score VAS, visual analog scale; SPADI, Shoulder Pain and Disability Index, a validated measure for shoulder disorders

Adapted from Singh JA, et al. American College of Rheumatology Meeting, 2007.¹

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