Efficacy of Intra-Articular Botulinum Toxin Type A in Painful Knee Osteoarthritis: A Pilot Study

Department of Physical Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA.
PM&R (Impact Factor: 1.53). 04/2010; 2(4):268-76. DOI: 10.1016/j.pmrj.2010.02.011
Source: PubMed


To evaluate the efficacy and safety of botulinum toxin type A (BoNT-A) injected intra-articularly in 60 subjects with moderate pain and functional impairment secondary to knee osteoarthritis. The study investigators hypothesized that intra-articular BoNT-A would result in statistically significant improvements in pain and function at 8 weeks.
Double-blind, randomized, single tertiary care academic medical center trial with 6-month follow-up.
Sixty patients aged 40 years or older with painful osteoarthritis of the knee who had failed physical therapy, medications, and/or injection therapy presenting to the musculoskeletal or orthopedic outpatient clinics at a large tertiary care medical institution. All 60 patients completed 8-week follow-up, but only 32 patients completed the 26-week follow-up.
Subjects were randomized to receive a single injection of corticosteroid, low-dose BoNT-A (100 units), or high-dose BoNT-A (200 units). Outcome measures were compared at baseline, 4, 8, 12, and 26 weeks after injection.
The primary outcome measure was pain visual analog scale (VAS) at 8 weeks. Secondary outcome measures included Western Ontario McMaster Arthritis Index, Short Form-36 scores, patient global assessment, 40-meter timed walk, and adverse effects.
The primary end point was pain VAS score at 8 weeks, which decreased within each group but only reached statistical significance in the low-dose BoNT-A group. In the intra-articular corticosteroid group, VAS decreased from 6.4 +/- 1.8 to 5.4 +/- 2.3 (P = .15); for low-dose BoNT-A, from 6.6. +/- 1.9 to 4.5 +/- 2.2 (P = .01); and for high-dose BoNT-A, from 6.6 +/- 1.4 to 5.9 +/- 2.4 (P = .15). All groups showed statistically significant improvements in Western Ontario McMaster Arthritis Index scores (pain, stiffness, function) at 8 weeks. No serious adverse events were noted in any group.
This pilot study supports a possible role for BoNT-A as a treatment option for symptomatic knee osteoarthritis; however, larger double-blind randomized studies are needed to determine whether BoNT-A is more effective than placebo in this patient population.

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    • "In three RCTs of a single IA injection of botulinum toxin in to 43-60 painful joints each (with painful OA or painful arthroplasty with OA as the underlying condition), clinically and statistically significant improvements in primary outcome of pain as well as extremity function (on WOMAC and shoulder indices) were noted in IA botulinum toxin group (with or without lidocaine) compared to control treatment (saline or saline plus lidocaine) [29-31]. In another RCT, IA botulinum toxin had efficacy similar to IA corticosteroid [32]. Botulinum toxin is known to inhibit substance P and calcitonin-gene related protein [33-36], the main mediators of neurogenic inflammation, a phenomenon of vasodilatation, protein extravasation, and stimulation of inflammatory cells induced by antidromic stimulation of primary afferent fiber [37]. "
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    ABSTRACT: Osteoarthritis (OA), the most common type of arthritis in the world, is associated with suffering due to pain, productivity loss, decreased mobility and quality of life. Systemic therapies available for OA are mostly symptom modifying and have potential gastrointestinal, renal, hepatic, and cardiac side effects. BMC Musculoskeletal Disorders recently published a study showing evidence of reparative effects demonstrated by homing of intra-articularly injected autologous bone marrow stem cells in damaged cartilage in an animal model of OA, along with clinical and radiographic benefit. This finding adds to the growing literature showing the potential benefit of intra-articular (IA) bone marrow stem cells. Other emerging potential IA therapies include IL-1 receptor antagonists, conditioned autologous serum, botulinum toxin, and bone morphogenetic protein-7. For each of these therapies, trial data in humans have been published, but more studies are needed to establish that they are safe and effective. Several additional promising new OA treatments are on the horizon, but challenges remain to finding safe and effective local and systemic therapies for OA. Please see related article:
    BMC Medicine 05/2012; 10(1):44. DOI:10.1186/1741-7015-10-44 · 7.25 Impact Factor
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    • "Recently, the efficacy and safety of botulinum toxin type A (BoNT-A) injected IA have been evaluated in 60 patients with moderate pain and functional impairment secondary to knee OA In this double-blind, randomized, single tertiary care academic medical center trial with 6-month follow-up, patients were randomized to receive a single injection of corticosteroid, low-dose BoNT-A (100 units), or high-dose BoNT-A (200 units) It was observed that VAS score decreased within each group, reaching statistical significance (p = 0.01) only in the low-dose BoNT-A group at 8 weeks In addition, all groups showed statistically significant improvements in WOMAC OA index scores (pain, stiffness, function) at 8 weeks (p-value not available), and no serious adverse events were noted in any group.[98] "
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    ABSTRACT: Osteoarthritis (OA), also called degenerative joint disease, is the most frequently occurring chronic musculoskeletal disease, particularly affecting the aging population. The use of viscosupplementation, i.e. intra-articular (IA) hyaluronic acid (HA) drug therapy, to treat OA, is growing worldwide, due to important results obtained from several clinical trials, which reported IA HA-related improvements in functional activity and pain management. This review is an update of the IA use of this compound in the treatment of OA, with clinical evidence from the last few years being discussed and used to delineate new trends for the future.
    12/2010; 11(1):13-27. DOI:10.2165/11539760-000000000-00000
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    • "Similar results were found in a randomized placebo-controlled trial of BoNT/A in chronic severe shoulder pain.17 Another randomized controlled trial found that intra-articular BoNT/A was as effective as intra-articular corticosteroids for chronic knee pain.28 Krug et al have reported significant analgesic effects of intra-articular BoNT/A in murine models of chronic inflammatory arthritis.16 "
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    ABSTRACT: To evaluate the analgesic effectiveness of intra-articular botulinum toxin Type B (BoNT/B) in a murine model of chronic degenerative arthritis pain. Chronic arthritis was produced in adult C57Bl6 mice by intra-articular injection of Type IV collagenase into the left knee. Following induction of arthritis, the treatment group received intra-articular BoNT/B. Arthritic control groups were treated with intra-articular normal saline or sham injections. Pain behavior testing was performed prior to arthritis, after induction of arthritis, and following treatments. Pain behavior measures included analysis of gait impairment (spontaneous pain behavior) and joint tenderness evaluation (evoked pain response). Strength was measured as ability to grasp and cling. Visual gait analysis showed significant impairment of gait in arthritic mice that improved 43% after intra-articular BoNT/B, demonstrating a substantial articular analgesic effect. Joint tenderness, measured with evoked pain response scores, increased with arthritis induction and decreased 49.5% after intra-articular BoNT/B treatment. No improvement in visual gait scores or decrease in evoked pain response scores were found in the control groups receiving intra-articular normal saline or sham injections. Intra-articular BoNT/B was safe, and no systemic effects or limb weakness was noted. This study is the first report of intra-articular BoNT/B for analgesia in a murine model of arthritis pain. The results of this study validate prior work using intra-articular neurotoxins in murine models. Our findings show chronic degenerative arthritis pain can be quantitated in a murine model by measuring gait impairment using visual gait analysis scores (spontaneous pain behavior) and joint tenderness scores (evoked pain responses). Reduction of joint pain seen in this study is consistent with our hypothesis of inhibition of release of pain mediators by intra-articular BoNT/B, supporting further investigation of this novel approach to treatment of arthritis pain with intra-articular neurotoxins.
    Journal of Pain Research 09/2010; 3:161-8. DOI:10.2147/JPR.S12520
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