Post-polio syndrome patients treated with intravenous immunoglobulin: a double-

blinded randomized controlled pilot study

E. Farbua, T. Rekanda, E. Vik-Moa, H. Lygrenc, N. E. Gilhusa, and J. A. Aarli

Presented by.dr.Cholis Nur Mutaslimah MPH

Puskesmas Mlati II

• Title / Judul :

“Post-polio syndrome patients treated with intravenous immunoglobulin: a double-blinded randomized controlled pilot study” 

• Author / Peneliti :

E. Farbua, T. Rekanda, E. Vik-Moa, H. Lygrenc, N. E. Gilhusa, and J. A. Aarli

• Publication by / Publikasi oleh :

European Journal of Neurology 2007, 14: 60–65

Background

• Post-polio syndrome (PPS) is characterized by new muscle weakness, atrophy, fatigue and pain developing several years after the acute polio. Some studies suggest an ongoing inflammation in the spinal cord in these patients. From this perspective, intravenous immunoglobulin (IvIg) could be a therapeutic option.

Method

s

• We performed a double-blinded randomized controlled pilot study with 20 patients to investigate the possible clinical effects of IvIg in PPS.

• Twenty patients were randomized to either IvIg 2 g/kg body weight or placebo. Primary endpoints were changes in pain, fatigue and muscle strength 3 months after treatment. Surrogate endpoints were changes in cerebrospinal fluid (CSF) cytokine levels. Secondary endpoints were pain, fatigue and isometric muscle strength after 6 months.

Alur Penelitian

Result

Patients receiving IvIg reported a significantimprovement in pain during the first 3 months, but no change was noted for subjectivefatigue and muscle strength.

CSF levels of tumour necrosis factor-a (TNF-a) wereincreased compared with patients with non-inflammatory neurological disorders

In conclusion, in this small pilot study no effect was seen with IvIg treatment on muscle strength and fatigue, however IvIg treated PPS patients reported significantly less pain3 months after treatment. TNF-a was increased in the CSF from PPS patients.

The results are promising, but not conclusive because of the low number of patients

studied.

CRITICAL APPRAISAL AN ARTICLE ON TREATMENT OR PREVENTION

PICO Question

DOES THIS STUDY ADDRESS A CLEAR QUESTION?1. Were the following clearly stated:

Yes No Can’t Tell

Patients Post-polio syndrome

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Intervention An intravenous immunoglobulin (IvIg)

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Comparison Intervention Placebo - -Outcome(s) Primary : changes

in pain, fatigue and muscle strength 3 months after treatmentSurogate : changes incerebrospinal fluid (CSF) cytokine levelsSecondary : pain, fatigue and isometric muscle strength after 6 months

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ValidityARE THE RESULTS OF THIS SINGLE TRIAL VALID?A. The main questions to answer:

 Yes

 No

 Can’t Tell

2. Was the assignment of patients to treatments randomised?Apakah penetapan pasien untuk mendapatkan pengobatan secara acak?

Yes – on page 2, 1st line under randomization and blinding :“The hospital pharmacy prepared a randomizationscheme with 20 notes marked with either IvIg or placebo”

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3. Was the randomisation list concealed? Can you tell?Apakah daftar pengacakan tersembunyi? Dapatkah Anda memberitahu?

Yes – on page 2, line 6-10 under randomization and blinding:“Study patients and study personnel were blinded throughout the study. The blinding scheme was kept by the pharmacy and was not broken during the trial, but there was a possibility for opening in case of absolute necessity (not done)”

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4. Were all subjects who entered the trial accounted for at it’s conclusion?Apakah semua subjek yang masuk penelitian diperhitungkan di kesimpulan?

Yes – on page 3, 1st line under Result : “Twenty patients (13 women and seven men) were included, and randomized to either IvIg or placebo with10 patients in each group. All of them completed thetrial (Fig. 1).” And Figure 1. Progress of post polio syndrome (PPS) patients enrolled in the study.

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5. Were they analysed in the groups to which they were randomised, i.e. intention-to-treat analysis?Apakah mereka dianalisis dalam kelompok-kelompok yang mereka diacak, yaitu intention-to-treat analysis? 

Yes – on page 3, line 4-6Under Statistical analyses: “The data were analysed using linear regression by randomization group and adjusted forbaseline value. Adverse events were analysed with unpaired t-tests. There was no adjustment for multiple comparisons.And Table 2 Clinical results before and after treatment of post polio syndrome (PPS) patients.

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6. Were subjects and clinicians ‘blind’ to which treatment was being received, i.e. could they tell?Apakah subjek dan dokter 'buta' terhadap pengobatan yang diterima, yaitu bisakah mereka ceritakan?

Yes – on page 2, line 6-10 under randomization and blinding:“Study patients and study personnel were blinded throughout the study. The blinding scheme was kept by the pharmacy and was not broken during the trial, but there was a possibility for opening in case of absolute necessity (not done)”

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7. Aside from the experimental treatment, were the groups treated equally?Selain dari pengobatan eksperimental, apakah kelompok diperlakukan sama?

Yes – on page 2, one paragraph under Study visits“There were five scheduled visits. All patients were screened for serum IgA before entry. The patients were again examined 3 and6 months after treatment. The same investigations wereperformed, but no CSF examination. One physiotherapist performed all muscle strength measurements forall the patients.”

   

8. Were the groups similar at the start of the trial?Apakah kelompoknya yang sama pada awal percobaan?    

Yes – on page 3,Figure 1. Progress of post polio syndrome (PPS) patients enrolled in the study. And Table 2 Clinical results before and after treatment of post polio syndrome (PPS) patients.

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Importance     

9. How large was the treatment effect?How were the results expressed .seberapa besar efek pengobatan?Bagaimana hasil diungkapkan.

Besarnya efek terapi IvIg terukur dari nilai p dan CI yang tercantum pada tabel 2. Clinical results before and after treatment of post polio syndrome (PPS) patients halaman 4 dan tabel 3. TNF-a, and IL-6 before and after treatment of post polio syndrome (PPS) patients halaman 5. Efek terapi di ukur dari tiga outcome atau hasilnya; Primary endpoint : perubahan nyeri, fatigue dan kekuatan otot setelah 3 bulan. Hasil statistik pada skala nyeri pada saat 3 bulan setelah terapi mengalami perubahan yang signifikan terlihat dari nilai p: 0,0001 (p< 0,05) dan CI 1.7–4.2, Untuk perubahan fatigue dan kekuatan otot tidak mengalami perubahan yang signifikan terlihat dari nilai p : 0,44 > 0,05 dan CI 18.4–108.3Surogate endpoint: perubahan level sitokin pada LCS. Hasil Statistik pada tabel 3 menunjukan ada perubahan yang signifikan pada TNF tumour necrosis factor-a (TNF-a) di LCS nilai p 0,028, Secondary endpoint : perubahan nyeri, fatigue dan isometrik otot setelah 6 bulan. Tidak terdapat perbedaan yang signifikan antara permberian IvIg dengan placebo.

10. How precise were the results?Were the results presented with confidence intervals?Bagaimana ketepatan hasilnya?Apakah hasil yang disajikan dengan interval kepercayaan? 

Ya. Hasil disajikan dengan interval kepercayaan di tabel 2 dan tabel 3.CI pada tiap hasil statistik di tabel 3 menunjukkan angka yang sempit. Hal ini menunjukkan sampel penelitian ini mewakili populasi target atau populasi umum. CI pada tiap hasil statistik di tabel 2 menunjukkan angka yang lebar. Hal ini menunjukkan sampel penelitian ini tidak mewakili populasi target atau inferensi lemah. 

   

CAN I APPLY THESE VALID, IMPORTANT RESULTS TO MY PATIENT?

Yes No Can’t tell

11. Do these results apply to my patient?Is my patient so different from those in the trial thatthe results don’t apply?How great would the benefit of therapy be for myparticular patient? 11. Apakah hasil ini dapat diaplikasikan untuk pasien saya?Apakah pasien saya begitu berbeda dengan yang ada di percobaan yang hasil tidak berlaku?seberapa besar akan manfaat terapi bagi pasien tertentu?   

Ya. Hasil penelitian ini bisa di aplikasikan pada pasien saya, dari hasil penelitian ini kita bisa menjelaskan bahwa terapi IvIg pada PPS memberikan hasil signifikan pada perubahan nyeri setelah 3 bulan terapi.

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12. Are my patient’s values and preferences satisfied bythe intervention offered?Do I have a clear assessment of my patient’s valuesand preferences?Are they met by this regimen and its potentialconsequences? 12. Apakah nilai dan pilihan/keinginan pasien dipuaskan dengan intervensi yang ditawarkan?Apakah saya memiliki penilaian yang jelas dari nilai-nilai pasien saya dan keinginannya?Apakah mereka dipenuhi oleh regimen ini dan potensinyakonsekuensi?

- Tidak. Hasil penelitian ini belum bisa memuaskan keinginan pasien karena terapi IvIg belum bisa mengurangi nyeri, fatigue dan meningkatkan kekuatan otot pada pasien PPS.

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Applicable

Conclusions

• Valid, Importance, Not applicable

TERIMAKASIH