Nelly Ziade-Zoghbi, MD, MPH Rheumatology department, Hotel-Dieu de France IV therapy for radicular pain A literature review and retrospective analysis

Nelly Ziade-Zoghbi, MD, MPH

Rheumatology department, Hotel-Dieu de France

IV therapy for radicular pain

A literature review and retrospective analysis of a case series at HDF

1- Literature review of IV treatments in radiculopathies

2- Case series at HDF: IV pentoxifylline in radiculopathies

Agenda2



Agenda3

4

www.pubmed.com

NSAIDs

Ketoprofene 100 mg / 8hrs for 3 days transcient effect

5

Etienne JC. Gaz Med 1986

Corticosteroids

RCT, sciatica < 6 weeks 65 patients

High-dose pulse methylprednisolone (500mg)

Transcient effect / small magnitude No effect on functional disability

6

Finckh et al, Spine 2006

Anti-TNF alpha

Role of anti-TNF alpha in the pathogenesis of the disco-radicular conflict

[Rannou F, Revel M. L’actualite rhumatologique 2005] [Mulleman et al. Joint Bone Spine 2006]

One RCT: 40 pts suffering from LS (2-12 wks) one infliximab infusion 1-year follow-up Improvement 67% versus 63% (p 0.72) Benefit+with Modic changes at symptomatic level 20% surgery

[Korhonen, Spine 2005]

7

What about Pentoxifyllin?

PTX is a PDE4 inhibitor increasing intracellular cAMP and stimulating PKA activity.

Primary actions: PTX increases red blood cell deformability, reduces blood viscosity and decreases the potential for platelet aggregation and thrombus formation

It is also a known inhibitor of TNF-alpha

8

Marques et al. Am J Respir Critic Care Med 1999

Evidence from PTX

Effects in experimental nerve injury Intraperitoneal PTX in rats with crushed

sciatic nerve Electrophysiologic studies 3 weeks later:

better amplitudes of compound muscle action potentials

Suggests positive effect on axon regeneration

9

Baykal el al. Turk J Med Sci 2002.

Evidence from PTX

Effects on nerve conduction velocity and blood flow in diabetic rats 2 weeks PTX Diabetic deficits in sciatic motor and

saphenous sensory nerve conduction velocity were 56.5% and 69.8% corrected, respectively

Sciatic endoneurial blood flow was 50.4% corrected

10

Flint et al. Int J Experimental Diab Res 2000



Agenda11

12

Baseline demographic characteristics

Age in years (SD) 57.64 (13.68 )

Male sex 8 [28.6%]

Smoking 4 [14.3%]

Diabetes 3 [10.7%]

13

Baseline clinical characteristics

Duration of symptoms in weeks [range]

45.68 [2-160]

SLR (Lasegue) sign < 30 degrees 6 [21%]

Controlateral SLR (Lasegue) sign < 30 degrees 2 [7%]

Sensory deficit 3 [11%]

Motor deficit (but => 3/5) 12 [43%]

Urine incontinence 2 [7%]

At least one reflex absent 10 [36%]

29%

18%

7%18%

14

PreviousTreatments

Protocols

Protocol N (%)

PTX 900 mg/day IV for 3 days followed by 1200 mg po /day

13 (46.4%)


3 (10.7%)


8 (29%)

PTX 900 mg/day IV for 3 or 4 days 4 (14.3%)Associated treatment N (%)

NSAIDs 14 (50%)

Analgesics 19 (67.8%)

Muscle relaxants 6 (21.4%)

Local injections (epidural / foraminal) 10 (35.7%)

Corticosteroids (oral / IV) 7 (25%)

15

Δ VAS (%)

-60

-50

-40

-30

-20

-10

0

Δ VAS radicular pain Δ VAS back pain

Immediately

At one month

Last Follow-up

16

38 months[3-84]

VAS response categories over time

0%

20%

40%

60%

80%

100%

Immediately At one month Last Follow-up

80-100%

60-79%

40-59%

20-39%

0-19%

17

Outcomes

Mean time to improvement

N (SD)

2.2 weeks (3.1)(36% in the following

week)

Mean time to returning to normal activities

3.56 weeks (4.1)

Willingness to repeat treatment if needed

48%

Surgery during follow-up 4 patients (14%)

18

Adverse events

AE N (%) N leading to discontinuation

Nausea / Vomiting

6 (21%) 1

Hypotension 3 (11%) 1

Tremor 1 (4%) 0

Skin rash (1) 4% 1

Fatigue (2) 7% 0

At least one AE

9 (32%) 3 (11%)

19

Who benefits more?

Baseline characteristics Good Responders*

Non responders

**

p

Age (years) 55 60 0.18

Male Sex (%) 36 18 0.41

Smokers (%) 0 40 0.03

Diabetics (%) 7 18 0.22

Duration of symptoms (weeks) 8.14 14.4 0.28

Motor deficit (%) 57 27 0.44

Sensory deficit (%) 21 0 0.08

SLR (Lasegue sign) < 30 deg (%)

29 18 0.12

Previous NSAIDs (%) 79 55 0.05

Previous local injections (%) 36 55 0.27

20

*Good responders = Δ VAS above median (higher range of response)**Non-responders = Δ VAS below median

Differences in Protocols

Good Responders*

Non responders**

p

PTX Protocol (% 5 days PTX + po)

14 45 0.58

Associated loca injection (%) 43 36 0.29

Associated muscle relaxants (%)

21 18 0.34

Associated analgesics (%) 64 82 0.69

Associated NSAIDs (%) 71 27 0.02

21


Role of associated NSAIDsBaseline characteristics NSAIDs + (14

pts)NSAIDs – (14

pts)P

Age (years) 53.43 61.86 0.10

Male Sex (%) 43 14 0.21

Smokers (%) 21 7 0.60

Diabetics (%) 7 14 0.33




Lasegue sign < 30 deg (%) 36 7 0.17


Previous epidural inj (mean nb) 36 50 0.70

22

Outcomes NSAIDs + NSAIDs - p

Δ VAS radicular pain (immediate) -53.85% -40.83% 0.77

Δ VAS radicular pain (at one month) -66.15% -45.42% 0.45

Δ VAS radicular pain (last follow-up) -72.69% -32.50% 0.02

Summary of main results

Δ VAS radicular pain around 50% (immediate and late response)

Good responders tend to be younger, male and non-smokers

Response at least partially explained by associated / previous NSAIDs

23

Study limitations

Retrospective analysis (recall bias) Small number of patients Different treatment protocols Different treatments associations (open study) No placebo arm / No blinded treatment

24

Study strenghts

Very few lost to follow-up (10.7%)

Evaluation of initial hospital chart + telephone contact with patients

Careful identification of all associated treatments

Careful identification of tolerability profile

25

Conclusion

Need in practice for a safe and efficacious treatment in resistant radiculopathies

Pentoxifylline / Anti-TNF family needs further dedicated well-designed studies, that takes into account associated treatments, especially NSAIDs

26

Thank you for your attention

28

Back-up29

Immediate response


Non responders

**

p

Age (years) 57 57.8

Male Sex (%) 20 40

Smokers (%) 0 40

Diabetics (%) 13 10

Duration of symptoms (weeks) 10.8 11.1

Motor deficit (%) 73 0

Sensory deficit (%) 20 0

Lasegue sign < 30 deg (%) 7 50

Previous NSAIDs (%) 60 80

Previous epidural inj 47 40

30


Immediate response

Good Responders*

Non responders**

p

PTX Protocol (5 days PTX + po)

20 36

Associated Epidural injection

33 50

Associated NSAIDs 47 60

Associated muscle relaxants

13 30

Associated analgesics 60 90

31


One month response


Non responders

**

p

Age (years) 53.60 61.33

Male Sex (%) 31 25

Smokers (%) 0 33

Diabetics (%) 8 17

Duration of symptoms (weeks) 11.23 10.58

Motor deficit (%) 69 17

Sensory deficit (%) 23 0

Lasegue sign < 30 deg (%) 15 33

Previous NSAIDs (%) 77 58

Previous epidural inj (mean nb) 38 50

32


One month response

Good Responders*

Non responders**

p


23 33


38 42

Associated NSAIDs 62 42


23 17

Associated analgesics 61 83

33


Who benefits more?


Non responders

**

p

Age (years) 55.3 57.9 0.64

Male Sex (%) 36 20 0.4

Smokers (%) 0 40 0.0095

Diabetics (%) 7 10 0.8




Lasegue sign < 30 deg (%) 20 29 0.77


Previous epidural inj (mean nb) 0.79 1.7 0.51*Good responders = Δ VAS above median (higher range of response)**Non-responders = Δ VAS below median

34

Differences in protocols

Good Responders*

Non responders**

p


14% 50% 0.17


43% 30% 0.52

Associated NSAIDs 71% 30% 0.044


21% 20% 0.93

Associated analgesics 64% 90% 0.15

35

Mean Δ VAS radicular pain: No increase in response with PTX dose

36

Median ΔVAS response over time

37

Responders categories38

MEDIAN50%50%

90%90%

70%70%

Documents

Nelly Ziade-Zoghbi, MD, MPH Rheumatology department, Hotel-Dieu de France IV therapy for radicular pain A literature review and retrospective analysis