limb pain (tendonitis, osteoarthritis, plantar fasciitis ... mckinsey & company, and teva...
TRANSCRIPT
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Limb Pain (Tendonitis, Osteoarthritis, Plantar Fasciitis, Piriformis Syndrome)
Zahid H. Bajwa, M.D.Director, Boston Headache Institute Director, Clinical Research, Boston PainCareWaltham, MA [email protected] Board Certification American Board of Psychiatry and Neurology (ABPN-Neurology)Board Certified in Pain Medicine (ABA-ABPN)American Board of Pain MedicineBoard Certified in Headache Medicine
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Disclosures
§ Research support: Amgen plc § Contributor: to Up-to-Date, Headache and Pain
Sections and the textbook Principles and Practice of Pain Medicine, 3rd Ed by Mc-Graw Hill
§ Consultant: AstraZeneca, Depomed, Inc., GLG Pharma, Guidepoint Global LLC, Kaléo, Inc., MediaCorp, McKinsey & Company, and Teva Pharmaceuticals
§ Data and Safety Monitoring Board (DSMB): Boston Scientific for Spinal Cord Stimulator (SCS) Systems
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Questions
1. Which limb pain condition has the strongest literature supporting the use of botulinum toxin? a. Carpal tunnel syndrome b. Reflex sympathetic dystrophy c. Hip pain d. Lateral epicodylitis e. Shoulder pain
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Questions
2. What is the most common dose range of onabotulinumtoxinA used in clinical trials for joint pain? a. 5 to 10 units b. 25 to 50 units c. 50 to 100 units d. 100 to 200 units e. 300 to 500 units
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Questions
3. True or False. The most common side effect reported in clinical trials after botulinum toxin injections for epicodylitis was grip weakness. § True § False
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Questions
4. Given limited data regarding the use of botulinum toxin injections, what is most appropriate statement? a. There are no significant data supporting the use of
botulinum toxin in the treatment of non-spastic limb pain. b. Studies demonstrate promising results in the treatment
of arthritic joint pain. c. Botulinum toxin can be helpful in painful limb conditions
involving muscle, tendon, and/or fascia only. d. Joint injections are commonly associated with reported
limb weakness. e. Knee injections tend be associated with extensor and not
flexor weakness.
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Botulinum Toxin Therapy for Joint and Limb Pain
§ Shoulder Pain
§ Hip Pain, Piriformis Syndrome
§ Knee Pain
§ Epicondylitis
§ Plantar Fasciitis
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Shoulder Pain
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Long Term Effects of Intra-articular Botulinum Toxin A for Refractory Joint Pain
• Open label, prospective • 9 subjects (osteoarthritis, RA, and psoriatic arthritis)
• Onabot (Botox) 50-100 units intra-articular
• Duration of effect 3 to 12 months
• No immediate or delayed adverse effects
MohwaldML,etal.NeurotoxRes.2006Apr;9(2-3):179-188.
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Long Term Effects of Intra-articular Botulinum Toxin A for Refractory Joint Pain
67%
42%
Flexion AbducEon
IncreasedAc0veRangeofMo0on
(p<0.01)
MohwaldML,etal.NeurotoxRes.2006Apr;9(2-3):179-188.
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Long Term Effects of Intra-articular Botulinum Toxin A for Refractory Joint Pain
8.2
2.4
Pretreatment PosJreatment
Reduc0oninShoulderPain
(p<0.001)
MohwaldML,etal.NeurotoxRes.2006Apr;9(2-3):179-188.
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Intra-articular Botulinum Toxin Type A: A New Approach to Treat Arthritis Joint Pain
§ Double blind, placebo controlled
§ 36 Subjects with shoulder pain refractory to NSAIDS, intra-articular steroid injection
§ Onabot (Botox) 100 units+lidocaine vs saline+lidocaine (Intra-articular)
§ Response measured at 4 weeks
MahowaldML,etal.Toxicon.2009;54(5):658-667.
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Intra-articular Botulinum Toxin Type A: A New Approach to Treat Arthritis Joint Pain
61%
31%
Onabot Saline
PainReduc0onat4WeeksPostTreatment
(p<0.002)
MahowaldML,etal.Toxicon.2009;54(5):658-667.
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Intra-articular Botulinum Toxin Type A: A New Approach to Treat Arthritis Joint Pain
61%
31%
Onabot Saline
>30%reduc0oninpain
MahowaldML,etal.Toxicon.2009;54(5):658-667.
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Intra-articular botulinum toxin A for Refractory Shoulder Pain: a Randomized, Double-blinded,
Placebo-controlled Trial
§ Double blind, placebo controlled
§ 43 Subjects with moderate-severe arthritis shoulder pain
§ Onabot (Botox) 100 units/lidocaine vs saline/lidocaine
§ Reduction of pain at one month s/p injection – Reduction in pain on VAS: Onabot -2.4 vs saline -0.8 (p=0.014)
– Improvement in SF-36 scores: Onabot (p</=0.035)
– Clinically meaningful pain relief: Onabot 61% vs saline 36% (p=0.22)
SinghJA,etal.TranslRes.2009;153(5):205-216.
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Hip Pain
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Piriformis Muscle
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Inflamed Sciatic Nerve
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Piriformis and Sciatic
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Piriformis Injection
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Botulinum toxin in Piriformis Syndrome
Authors Study Childers Martin K, et. al. *
Botulinum toxin type A use in piriformis muscle syndrome: A pilot study. Am J Phys Med Rehabil. 2002
Fishman Loren M. et. al. *
Botox and physical therapy in the treatment of piriformis syndrome. Am J Phys Med Rehabil. 2002
Lang Amy M. Botulinum Toxin Type B in Piriformis Syndrome. Am J Phys Med Rehabil. 2004
*RDBPC
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Study Design – Single center, double blind, single group, crossover – n=10 – Two 10 week treatment arms with 4 weeks washout – BoNT-A (Botox) 100 U vs. preservative free normal
saline
ChildersMKet.al.Am.J.Phys.Med.Rehabil.2002.81(10)751-9
BotulinumToxinUseinPiriformisSyndrome:APilotStudy
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BotulinumToxinUseinPiriformisSyndrome:APilotStudy
Assessment– VASreporEngof: PainIntensity
Spasm
InterferencewithAcEviEes
Distress
– H-reflexmeasurementside-side/pre-postBoNT/A
– Pain-on-moEonanalysis(painperceivedduringasteppingtask)
Am.J.Phys.Med.Rehabil.2002.81(10)751-9.ChildersMKet.al.Am.J.Phys.Med.Rehabil.2002.81(10)751-9
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§ Results – Functional improvement noted with BoNT/A injections
(p<0.05) – VAS decreases were detected under every category in
BoNT/A treated group (p<0.05) – Similarities in H reflex latencies between groups
• Before injection of study treatments • Following injection of study treatments
– Motion analyses also failed to detect differences between baseline and experimental groups
– No adverse events were reported § Authors’ Conclusions
– “VAS data suggest that intramuscular piriformis injection with 100 units of botulinum toxin type A (Botox) can reduce pain to a greater extent than similar injections with vehicle alone.”
ChildersMKet.al.Am.J.Phys.Med.Rehabil.2002.81(10)751-9
BotulinumToxinUseinPiriformisSyndrome:APilotStudy
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BoNT-A and Physical Therapy in the Treatment of Piriformis Syndrome
§ Study Design – Double blind, placebo controlled, clinical trial – n=87, (n=67 after exclusion of those with <2 follow up visits) – BoNT/A (Allergan) 200 U, Lidocaine with steroid, or placebo – Standard physical therapy protocol twice weekly X 12 weeks – Examinations every 2 weeks – 1o endpoint: VAS Responses at two last visits (10 and 12 weeks)
§ Patient Selection – Piriformis syndrome was diagnosed when there were significant
discrepancies between anatomic position and FAIR position (per Snow BJ et. al. Neurology 1990;40(suppl 1):382)
Fishmanet.al.AmJPhysMedRehabil2002;81(12):936-42
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*T/L=triamcinoloneandlidocaine**Percentofsubjectswith50%ormoreimprovementateach
oftheirlasttwovisits
Injection No. of Patients
No. Improved % Improved **
T/L* 31 10 32
BoNT/A (Allergan) 21 13 65
Placebo 15 1 6
Fishmanet.al.AmJPhysMedRehabil2002;81(12):936-42
Results
BoNT-A and Physical Therapy in the Treatment of Piriformis Syndrome
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FishmanLM,et.al.BotoxandPhysicalTherapyintheTreatmentofPiriformisSyndrome
Authors’Conclusion:“BotoxandPhysicalTherapyweremoreeffecTveintreaTngPiriformisSyndromethaneitherT/LorplaceboinjecTonsinconjuncTonwithPhysicalTherapy.”NoAdverseeventswerereportedinthisstudy.
AmJPhysMedRehabil2002;81(12):936-42.Fishmanet.al.AmJPhysMedRehabil2002;81(12):936-42
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BoNT-B in Piriformis Syndrome
Study Design – Single center, outpatient, open label study – n = 20 – Follow ups at 2,4,8,12, and 16 weeks – 5000 units per piriformis (up to 10,000 units total dose
if bilateral injection) infiltrated with EMG guidance – Endpoints:
• Mean VAS for buttock and hip pain and for low back pain. • VAS for general and low back pain, pain radiating into lower
limbs, and tingling.
LangAM.AmJPhysMedRehabil.2004;83(3):198-202
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Results – Significant reductions in VAS – Patient rated pain improvement:
• 95% - fair to excellent • 75% - good to excellent
– Investigator rated efficacy: • 90% - fair to excellent • 55% - good to excellent
LangAM.AmJPhysMedRehabil.2004;83(3):198-202
BoNT-B in Piriformis Syndrome
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Safety – Six patients(30%) experienced mild to severe dry
mouth – Two patients (10%) experienced mild to moderate
flu like symptoms – Two patients (10%) reported visual disturbance
(10%) – One patient (5%) reported dizziness – One patient (5%) reported nausea – One patient (5%) reported GERD
LangAM.AmJPhysMedRehabil.2004;83(3):198-202
BoNT-B in Piriformis Syndrome
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Efficacy of Botulinum Toxin Type A Treatment of Functional Impairment of Degenerative Hip Joint:
Preliminary Results
§ Open label, prospective § 39 Subjects (41-82 y/0) with hip pain and osteoarthritis § Abobot (Dysport) 400 units injected into the ipsilateral
adductor longus/adductor magnus muscles
§ Improvement in Harris Hip Score at 2, 4, and 12 wks (p<0.0001)
§ Decrease in VAS pain scores at 2, 4, and 12 wks (p<0.001)
§ Improved hip mobility noted on exam
MarchiniCe,tal.JRehabilMed.2010:42(7):691-693.
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Knee Pain
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An Open Label Pilot Investigation of the Efficacy Of Botulinum Toxin Type A [Dysport] Injection in the
Rehabilitation of Chronic Anterior Knee Pain
§ Open label Pilot Study § 8 Subjects with >6 months of anterior knee pain, who
had failed conservative therapy § Obabot (Dysport) 300-500 units into distal 2/3 of VL
followed by home exercise program to improve recruitment of the VM
§ Subjects reported reduced knee pain and brace dependency
§ Subjects reported increased participation in sporting and daily living activities
SingerBJ,etal.DisabilRehabil.2006Jun15;28(11):707-713.
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Intra-articular Botulinum Toxin Type A: a New Approach to Treat Arthritis Joint Pain
§ Double blind, placebo controlled § 42 Subjects with knee pain refractory to NSAIDS, intra-
articular steroid injection § Onabot (Botox) 100 units+lidocaine vs saline+lidocaine
§ Knee pain reduction on McGill Pain Joint Inventory Scale: – Onabot superior to saline:
• 1 month (p=0.011) • 3 months (p=0.002)
MahowaldML,etal.Toxicon.2009;54(5):658-667.
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Intraarticular Botulinum Toxin A For Refractory Painful Total Knee Arthroplasty: A Randomized Controlled Trial
§ Randomized, Placebo controlled, triple-blinded
§ 49 subjects with painful total knee arthroplasty, – mean duration 4.5 years
§ Onabot (Botox) 100 units vs saline
§ Single intra-articular injection into painful knee
SingJA,etal.JRheumatol.2010Nov;37(11):2377-2386.
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Intraarticular Botulinum Toxin A For Refractory Painful Total Knee Arthroplasty: A Randomized Controlled Trial
§ Reduction in VAS rated pain:
– Onabot 71% vs saline 35% – s/p 2 months (p=0.28) s/p 3 and 4 months (p=0.019)
§ Duration of meaningful pain relief : – Onabot 39.6 days vs saline 15.7 days (p=0.045)
§ Onabot superior to saline: – Western Ontario McMaster Osteoarthritis Index physical function (p=0.026)
• Reduction in stiffness (p=0.004) and total score (p=0.024) – Reduction of pain subscale score on SF-36 (p=0.049)
SingJA,etal.JRheumatol.2010Nov;37(11):2377-2386.
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Treatment of Refractory Anterior Knee Pain Using Botulinum Toxin Type A (Dysport) Injection to the Distal Vastus Lateralis
Muscle: A Randomized Placebo Controlled Crossover Trial
§ Randomized placebo controlled crossover § 24 subjects with refractory anterior knee pain § Abobot (Dysport) 500 units vs saline injections the
vastus lateralis followed by home exercises focusing on re-training the vastus medialis
SingerBJ,etal.BrJSportsMed.2011Jun;45(8):640-645.
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Treatment of Refractory Anterior Knee Pain Using Botulinum Toxin Type A (Dysport) Injection to the Distal Vastus Lateralis
Muscle: A Randomized Placebo Controlled Crossover Trial
§ 14 subjects received BoNT-A and 10 placebo injection.
§ Improvement at 12 weeks was significantly greater for Abobot compared with placebo-injected subjects for:
§ AKPS (p<0.03) § pain on kneeling (p<0.004), § squatting (p<0.02) § level walking (p<0.04).
SingerBJ,etal.BrJSportsMed.2011Jun;45(8):640-645.
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Plantar Fasciitis
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Plantar Fascia Injection
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Treatment of Pain Attributed to Plantar Fasciitis with Botulinum Toxin A: A Short Term, Randomized, Placebo Controlled, Double-Blind Study
§ Double blind, placebo controlled
§ 27 Subjects (43 feet)
§ Onabot (Botox) 70 units
BabcockMS,et.al.AmJPhysMedRehabil.2005Sep;84(9):649-654.
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Treatment of Pain Attributed to Plantar Fasciitis with Botulinum Toxin A: A Short Term, Randomized, Placebo Controlled, Double-Blind Study
Improvement in all measurements at 3 & 8 weeks At 3 weeks: 39% decrease on the Pain Visual Analog Scale (p<0.005)
34% improvement of the Maryland Foot Score (p< 0.001)
40% increase in pressure algometry response (p<0.003)
Maintained at 8 weeks
No side effects reported
BabcockMS,etal.AmJPhysMedRehabil.2005Sep;84(9):649-654.
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Ultrasonographic Guided Botulinum Toxin Type A Treatment for Plantar Fasciitis: An Outcome-Based Investigation for Treating Pain and Gait Changes
§ Double blind, placebo controlled § 50 subjects with unilateral plantar fasciitis § Onabot (Botox) 50 units vs saline § Pain reduction on VAS in Onabot group superior to
placebo at 3 wks and 3 months (p<0.001) § Center of pressure velocity during loading in Onabot
group increased compared to placebo (p<0.05) § Fat pad thickness remained unchanged
HuangYC,etal.JRehabilMed.2010Feb;42(2):136-140.
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Randomized Controlled Study of the Efficacy of the Injection of Botulinum Toxin Type A versus Corticosteroids in
Chronic Plantar Fasciitis: Results at One and Six Months
§ Single blind, placebo controlled § 52 subjects § Onabot (Botox) vs corticosteroids § Outcomes based on Foot Health Square
Questionnaire results at 1 and 6 months
§ one month (improvement with botulinum toxin vs. corticosteroid: – pain 19.10/-6.84 (P = 0.001) – function 16.00/-8.80 (P < 0.001) – footwear 13.48/-7.95 (P = 0.004) – self-perceived foot health 25.44/-5.41 (P < 0.001).
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Treatment of Chronic Plantar Fasciitis with Botulinum Toxin A--An Open Pilot Study on 25 Patients
with a 14-Week-Follow-Up
§ Open label pilot study § 25 subjects refractory to conservative therapy § Dose finding: 6 subjects injected with Abobot
(Dysport) 100 units and 6 subjects injected with Abobot (Dysport) 200 units.
§ 13 subjects then injected with Abobot (Dysport) 200 units
§ A significant reduction of maximum and continuous pain was seen 2 weeks after injection in the group of 19 patients treated with 200 units BoNT A and persisted until the end of the follow-up
§ No adverse reactions reports
PlaczekR,etal.ZOrthopIhreGrenzgeb.2006Jul-Aug;144(4):405-409.Díaz-LlopisIV,etal,.ClinRehabil.2012Jul;26(7):594-606.
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Tennis Elbow
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Lateral Epicondyle Injection
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Treatment of Lateral Epicondylitis with Botulinum Toxin: A Randomized, Double-blind, Placebo-controlled Trial
§ Double blind, placebo controlled § 60 subjects
§ Onabot (Botox), 60 units vs. saline
§ Decreased pain at weeks 4 & 12
§ Mean decreased VAS 65 to 25 (p<0.006) at 4 wks
§ No significant difference in grip strength
§ 60% reported some weakness
WongSM,etal.AnnInternMed.2005Dec6;143(11):793-797.
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Onabot 60 units vs. Placebo Lateral Epicodylitis
65.5
25.3 23.5
66.2
50.5
43.5
0
10
20
30
40
50
60
70
Baseline 4wks 12wks
Onabot Placebo
WongSM,etal,AnnInternMed.2005Dec6;143(11):793-797.
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Botulinum Toxin Injection in the Treatment of Tennis Elbow: A Double-blind, Randomized, Controlled,
Pilot Study
§ Double blind, placebo controlled
§ 40 subjects (Failed steroid injection)
§ Onabot (Botox) 50 units vs. saline
§ IM injections were performed 5 cm distal to the maximum point of tenderness at the lateral epicondyle
§ Trend toward improvement at 3 months
§ No significant difference in grip strength
§ 60% reported some weakness § 12/18 reported extensor weakness
HaytonMJ,etal.JBoneJointSurgAm.2005Mar;87(3):503-507.
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Treatment of Chronic Radial Epicondylitis with Botulinum Toxin A: A Double-blind, Placebo-controlled,
Randomized Multicenter Study
§ Double blind, placebo controlled
§ 130 subjects
§ Abobot (Dysport) 60 units vs. saline
§ Decreased pain (VAS) at 2, 6, 12, and 18 weeks (=0.003)
§ Subjective improvement at 6 and 18 weeks (<0.001)
§ Improved grip strength in both groups
§ Extensor weakness at 2 weeks
PlaczekR,etal.JBoneJointSurgAm.2007Feb;89(2):255-260.
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Use of Anatomic Measurement to Guide Injection of Botulinum Toxin for the Management of Chronic
Lateral Epicondylitis: A Randomized, Controlled Trial
§ Double blind, placebo controlled
§ 60 subjects (refractory lateral epicondylitis)
§ Onabot (Botox), 60 units vs. saline
§ VAS (100 mm scale) at 4, 8, & 16 wks.
EspandarR,etal.CMAJ.2010May18;182(8):768-773.
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Pain score at rest
Baseline 48.8(23.7)
46.4(16.2)
2.3(−9.5to14.2) 0.010*
Week4 20.4(15.9)
34.5(12.2)
14.1(5.8to22.3)
Week8 17.9(18.0)
29.4(14.5)
11.5(2.0to21.4)
Week16 3.9(6.0)
16.7(10.5)
12.6(7.7to17.8)
Outcomemeasure
Group;mean(SD) Differenceinmean(95%CI)
pvalue(repeatedmeasurement)
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Pain score during maximum grip
Outcomemeasure
Group;mean(SD)Differenceinmean(95%CI)
pvalue(repeated
measurement)
Baseline 65.8(22.0) 65.0(18.3) 0.8(−10.9to12.6) 0.22
Week4 52.0(23.3) 57.4(18.2) 5.3(−6.8to17.5)
Week8 43.8(23.1) 51.5(20.1) 7.8(−4.8to20.4)
Week16 18.8(10.0) 30.6(15.6) 11.8(4.2to19.4)
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Pain score during maximum pinch
Baseline 42.6(26.5) 45.1(19.0) 2.4(−11.0to15.9) 0.004*
Week4 17.2(16.8) 32.7(12.6) 15.4(6.8to24.1)
Week8 12.2(14.9) 26.6(11.3) 14.4(6.8to22.2)
Week16 5.1(9.7) 13.6(8.3) 8.5(3.1to13.9)
Outcomemeasure
Group;mean(SD) Differenceinmean(95%CI)
pvalue(repeatedmeasurement)
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Reported Adverse Reactions
Adverse reaction; time frame
Group; no. of patients Botulinum toxin Placebo
Pain at injection site After injection 3 2 Weeks 0–4 7 2 Weeks 4–8 0 0 Weeks 8–16 0 0 Tingling sensation around injection site After injection 0 0 Weeks 0–4 5 0 Weeks 4–8 0 0 Weeks 8–16 0 0 Subjective feeling of muscle spasm around injection site
After injection 0 0 Weeks 0–4 8 0 Weeks 4–8 0 0 Weeks 8–16 0 0 Total 23 4
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Botulinum Toxin Therapy for Joint and Limb Pain Summary
§ Good data for BTX use in lateral
epicondylitis and knee pain
§ Evolving data for BTX in plantar fasciitis and shoulder pain
§ Minimal data for BTX in hip pain, Except Piriformis Syndrome
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Questions
1. Which limb pain condition has the strongest literature supporting the use of botulinum toxin? a. Carpal tunnel syndrome b. Reflex sympathetic dystrophy c. Hip pain d. Lateral epicodylitis e. Shoulder pain
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Questions
2. What is the most common dose range of onabotulinumtoxinA used in clinical trials for joint pain? a. 5 to 10 units b. 25 to 50 units c. 50 to 100 units d. 100 to 200 units e. 300 to 500 units
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Questions
3. True or False. The most common side effect reported in clinical trials after botulinum toxin injections for epicodylitis was grip weakness. § True § False
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Questions
4. Given limited data regarding the use of botulinum toxin injections, what is most appropriate statement? a. There are no significant data supporting the use of
botulinum toxin in the treatment of non-spastic limb pain. b. Studies demonstrate promising results in the treatment
of arthritic joint pain. c. Botulinum toxin can be helpful in painful limb conditions
involving muscle, tendon, and/or fascia only. d. Joint injections are commonly associated with reported
limb weakness. e. Knee injections tend be associated with extensor and not
flexor weakness.
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Thank You