Botulinum Toxin Type A May Do More than Make You Look Younger, May Make Your Joints Feel Younger Too

Newswise — A single injection of intra-articular botulinum toxin Type A may significantly decrease pain and improve shoulder function in osteoarthritis sufferers, according to researches presented this week at the American College of Rheumatology Annual Scientific Meeting in Boston, Mass.

Osteoarthritis is the most common joint disease affecting middle-age and older people. It is characterized by progressive damage to the joint cartilage—the slippery material at the end of long bones—and causes changes in the structures around the joint. These changes can include fluid accumulation, bony overgrowth, and loosening and weakness of muscles and tendons, all of which may limit movement and cause pain and swelling.

Injection of botulinum neurotoxin (commonly referred to by the brand name Botox) into joints is a promising new approach for treating sustained shoulder pain brought on by arthritis. An injection of neurotoxin in the joint may work by decreasing the release of certain proteins from the nerves in the joints—thereby decreasing the pain sensation in the joint.

Researchers recently studied the effectiveness of intra-articular botulinum neurotoxin versus placebo in patients with chronic shoulder pain, due to osteoarthritis or rheumatoid arthritis, who did not respond to corticosteroids or pain medication. These patients also were not candidates for shoulder arthroplasty.

Forty-three patients with moderate to severe arthritis pain (categorized as greater than 4.5 on a scale of zero to 10 with zero as no pain and 10 as the worst pain) were randomly placed in two groups and assessed at one, three and six months. The first group received intra-articular neurotoxin and lidocaine, while the second group received saline and lidocaine.

By comparing pain levels before beginning treatment to pain levels 28 days after the treatment, researchers found that pain levels were significantly lower in the patients receiving neurotoxin compared to placebo. Thirty-eight percent of patients receiving the injection of botulinum neurotoxin into the joint had at least a 30 percent reduction in pain score compared to only nine percent of patients in the placebo group. There was a trend toward a greater improvement in shoulder function in the botulinum toxin group, as compared to the placebo group at 28 days.

"This study provides the initial 'proof of concept' of effectiveness of botulinum toxin injection for relief of shoulder joint pain," says investigator in the study, Jasvinder Singh, MBBS, MPH; staff physician, Minneapolis VA Medical Center; assistant professor of medicine, University of Minnesota; visiting scientist and K -12 scholar, Mayo Clinic School of Medicine. "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."

The American College of Rheumatology is the professional organization for rheumatologists and health professionals who share a dedication to healing, preventing disability and curing arthritis and related rheumatic and musculoskeletal diseases. For more information on the ACR's annual meeting, see http://www.rheumatology.org/annual.

Editor's Notes: Dr. Singh will present this research during the ACR Annual Scientific Meeting at the Boston Convention and Exhibition Center from 9:00 " 11:00 am ET on Friday, November 9, 2007, in the Exhibit Hall.

Presentation Number: L4

Intra-articular Botulinum Toxin Type A (IA-BoNT/A) Significantly Decreases Shoulder Pain in Patients with Refractory Shoulder Pain due to Osteoarthritis: A Randomized Double-Blind Placebo-Controlled Trial

Jasvinder A. Singh, Maren L. Mahowald, Siamak Noorbaloochi. Minneapolis VA Medical center, Minneapolis, MN

Persistent shoulder pain is very common problem affecting over 5% of adult Americans each year. IA Neurotoxin injection for sustained analgesia is a promising new approach to persistent joint pain (J Neurotox Res: 2006;9:179-88), which may act by inhibiting vesicle release of neuropeptides such as Substance P and CGRP and disrupting nociceptor function to decrease pain.

Purpose: To report the efficacy data from the Double-blinded RCT of IA-BoNT/A vs. IA-placebo in patients with chronic, shoulder osteoarthritis (OA) pain refractory to intra-articular corticosteroids and oral analgesics, who were not candidates for shoulder arthroplasty.

Methods: 43 patients with moderate to severe OA pain (>4.5 on 0-10 numeric rating scale (NRS)) were randomized to two groups and assessed at baseline, 1-, 3- and 6-months: (1) 100 units IA-BoNT/A + lidocaine (BoNT/A group); or (2) saline + lidocaine (Placebo group). 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 and Shoulder Pain and Disability Index (SPADI) 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 >=30% pain relief (=clinically meaningful pain relief). We compared baseline to day 28 changes by using paired student's t-tests for continuous and chi-square for categorical outcomes.

Results: 43 shoulder joint in 37M (5 with bilateral shoulder joint injections) and 1F with mean age (Standard deviation) of 71±10 yrs were randomized: 21 BoNT/A, 22 Placebo. Both groups were comparable with regards to demographic and outcome variables at baseline. [Figure 1, Outcomes at Day 28 post-shoulder joint injection, available on request]

Primary Outcome Measure: At day 28, pain as measured by VAS pain, day pain on NRS and SPADI pain score were all significantly lower in the BoNT/A vs. placebo group (Table).

Secondary Outcome Measures: SPADI disability score was better at Day 28 in BoNT/A vs. placebo group with trend towards significance. 38% patients in BoNT/A vs. 9% in placebo group had >=30% reduction in SPADI pain score. A detailed analysis of adverse effects and duration of effects is in progress.

Conclusion: A single injection of IA-BoNT/A produced statistically significant and clinically meaningful decrease in moderate/severe refractory OA shoulder pain and tended to improve shoulder function. These data are very promising and provide further evidence supporting the efficacy of this novel neurotoxin therapy. A multi-center RCT is needed to confirm these findings.

Disclosure Block: J.A. Singh, TAP, Abbott, 2 Research grants; Travel grants from Allergan, 9 Other.