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Subcutaneous immunoglobulin in CIDP and MMN: a different long-term clinical response?
  1. Dario Cocito1,
  2. Aristide Merola1,
  3. Alberto Romagnolo1,
  4. Erdita Peci1,
  5. Antonio Toscano2,
  6. Anna Mazzeo2,
  7. Luca Gentile2,
  8. Massimo Russo2,
  9. Raffaella Fazio3,
  10. Massimiliano Filosto4,
  11. Gabriele Siciliano5,
  12. Erica Schirinzi5,
  13. Eduardo Nobile-Orazio6,
  14. Leonardo Lopiano1
  1. 1 Department of Neuroscience, University of Turin, Torino, Italy
  2. 2 Department of Neuroscience, Psychiatry and Anesthesiology, A.O.U. Policlinico “G. Martino”, Messina, Italy
  3. 3 Department of Neurology, IRCCS San Raffaele, Milano, Italy
  4. 4 Neuromuscular Diseases and Neuropathies Section, University and Neurological Clinic, A.O “Spedali Civili” of Brescia, Brescia, Italy
  5. 5 Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
  6. 6 Department of Translational Medicine, Neurology 2, University of Milano, IRCCS Istituto Clinico Humanitas, Rozzano, Milano, Italy
  1. Correspondence to Dr Dario Cocito, Department of Neuroscience University of Turin, Via Cherasco 15, 10126 Torino, Italy; dariococito101{at}

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Subcutaneous immunoglobulin (SCIg) has been recently proposed as an effective alternative to intravenous immunoglobulin (IVIg) for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN) treatment. The non-inferiority of SCIg over IVIg has been recently confirmed by a 4-month multicentre Italian observational study,1 where a similar efficacy was observed between the two therapies, with the SCIg showing possible advantages of stable plasmatic concentration2 and independence from hospital care. Here we report the 2-year experience of six Italian Neurological Centres, describing the long-term clinical outcomes of 66 patients (45 CIDP and 21 MMN) who were shifted from IVIg to SCIg.


All the CIDP and MMN patients treated with SCIg between 2009 and 2014 were considered, including patients with a previous documented response to IVIg (at least 6 months), and a wear-off effect between each IVIg infusion documented by a worsening of at least 1 point at the Overall Neuropathy Limitation Scale (ONLS).

Adherence to therapy was the primary outcome measure, while quality of life and clinical predictors of long-term disability were analysed as secondary outcomes. The clinical assessments were regularly performed by means of the ONLS, the Medical Research Council (MRC) scale in eight-muscle group bilaterally, and Life Quality Index (LQI). Clinical worsening was defined as increase of ≥1 ONLS point, requiring augmentation of SCIg dose, SCIg/IVIg combination therapy, or a return to IVIg for stabilising the clinical conditions. SCIg was administered at the patient's home, as previously described,1 converting the IVIg dose to an equivalent SCIg dose (20% solution of immunoglobulin ready-to-use) delivered via a programmable infusion pump. All patients signed a written informed consent, and ethical committee approval was obtained (CEI—629 Prot. n 0010675, 25 January 2013). Statistical analyses were carried out utilising the Wilcoxon, Mann-Whitney and Friedman non-parametric tests, Cox proportional hazard regression model and Kaplan Meier survival analyses.


At the baseline, CIDP and MMN patients showed a similar age (56.49±14.65 vs 56.86±13.99 years; p: 0.886) and disease duration (9.60±6.02 vs 9.96±6.18 years; p: 0.787), with only little differences in therapy duration (22.44±10.49 vs 27.90±14.92 months; p: 0.155) and IVIg doses (78.35±28.56 vs 87.30±27.90 g; p: 0.105). No concomitant diseases potentially influencing the neuropathy course (ie, diabetes) were reported.

Over a follow-up observational period of 24.18±12.23 months (range: 6–65), the overall adherence to SCIg therapy was 100% (66/66) at 4 months, 92.3% (60/65 patients) at 12 months, 85.7% (48/56) at 18 months, and 75.6% (31/41) at 24 months (figure 1A). In four CIDP cases and in four MMN cases, the therapy was discontinued for a worsening of clinical conditions. The remaining four discontinuations were related to cutaneous side effects (2 CIDP patients, after 21 and 37 months), personal preference for IVIg (1 CIDP case, after 6 months) and logistic difficulties (1 CIDP case, after 6 months). In addition, 4.4% of CIDP (2/45) and 23.8% of MMN (5/21) patients required a SCIg dosage increase or an administration with IVIg infusions, with an overall increase of immunoglobulin dosage of 3.04%: 2 CIDP patients had an increase in the SCIg dosage by 20% after 6 and 38 months; one MMN patient had an increase in the dosage by 15% after 24 months, and 4 MMN patients required an administration with IVIg monthly infusions at half the dosages previously administered, after 1 month (2 patients), and 6 and 12 months of therapy.

Figure 1

(A) Survival curves representing the long-term adherence to SCIg therapy in CIDP (solid line) and MMN (dashed line); (B) LQI showed the higher rate of amelioration in CIDP, although a significant improvement versus baseline values was also reported in MMN patients. Therapy setting (section III), and patient's perception of treatment costs (section IV) also improved in the patients who dropped out. CIDP, chronic inflammatory demyelinating polyradiculoneuropathy; LQI, Life Quality Index; MMN, motor neuropathy; SCIg, subcutaneous immunoglobulin.

Overall, the CIDP and MMN groups showed a different rate of clinical worsening during follow-up (p: 0.02), with 13.3% of CIDP (6/45) and 42.9% of MMN (9/21) patients reporting a SCIg dose increase, SCIg+IVIg combination therapy, or a return to IVIg therapy, in order to obtain stabilisation of clinical conditions (figure 1A).

Concerning the LQI, a global improvement was observed after the switch from IVIg to SCIg (figure 1B). Also, patients requiring a SCIg dose increase showed a significant LQI improvement (p: 0.048 for section I; p: 0.043 for section II; p: 0.042 for section III and p: 0.048 for section IV), while patients who dropped out (due to therapy inefficacy or side-effects) did not improve at the sections I and II stages, but showed an amelioration at the sections III (p: 0.046) and IV (p: 0.046) stages.

Finally, no significant predictors of long-term adherence to therapy were observed among the main clinical baseline features, including age (HR: 1.06; p: 0.720), disease duration (HR: 1.01; p: 0.687), immunoglobulin doses (HR: 1.05; p: 0.130), ONLS (HR: 1.01; p: 0.510) and MRC (HR: 1.07; p: 0.835).


This long-term retrospective multicentre study reports the clinical data of 45 CIDP and 21 MMN patients treated with SCIg for an average follow-up period of 2 years, showing an overall adherence to therapy of 75.6% at 24 months. A higher global personal satisfaction was observed during the treatment with SCIg, as a significant improvement of the quality-of-life measures was reported in almost all patients, even in those who returned to IVIg. CIDP and MMN showed a heterogeneous clinical response, while no other significant predictor of long-term outcome was found among the clinical and demographic baseline features, and only two drop-out cases for side effects were observed.1 However, comparisons between CIDP and MMN should be cautiously interpreted. In both diseases, an autoimmune response against nerves is indicated, even though the precise mechanisms have not yet been established. Modifications in the actions of this response between SCIg and IVIg may, theoretically, point to the differences observed in the clinical outcome of the two diseases.

An overall increase of immunoglobulin consumption of 3.04% was reported after the switch from IVIg to SCIg, with only minimal differences between the final costs of the two therapies.1 Experimental data from patients with primary immunodeficiency suggest that a SCIg dose adjustment might be necessary to obtain the same area under the curve of IVIg serum levels.2 Still, the optimal dosage and frequency of immunoglobulin administration in chronic dysimmune peripheral neuropathies has yet to be demonstrated,3–5 and further studies with immunoglobulin plasmatic dosages seem necessary to evaluate the pharmacokinetic aspects of the pulsatile versus continuous, or intravenous versus subcutaneous means of administration.

In conclusion, despite the major limitations of a retrospective unblinded observational analysis, and the assessment based on a limited battery of clinical scales, our findings seem to suggest that SCIg is a significantly effective therapeutic option for chronic dysimmune peripheral neuropathies, with some possible differences in CIDP and MMN.


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  • Contributors DC was involved in the organisation and execution of the research project; design, execution, review and critique of the statistical analysis; writing of the first draft and the review and critique of the manuscript. AM was involved in the execution of the research project; execution, review and critique of the statistical analysis; writing of the first draft and review and critique of the manuscript. AR was involved in the execution of the research project; execution, review and critique of the statistical analysis; review and critique of the manuscript. EP was involved in the execution of the research project; execution of the statistical analysis. AT, AM, LG, MR, RF, MF, GS, ES and EN-O were involved in the execution of the research project; review and critique of the manuscript. LL was guarantor; and involved in the conception and organisation of the research project; critique of the statistical analysis; and review and critique of the manuscript.

  • Competing interests DC received honoraria for lecturing from Baxter, CSL Behring, and Kedrion; he received personal compensation for serving on the Advisory Board of CSL Behring, Kedrion and Lilly and travel grants to attend scientific meetings from Baxter, Grifols, Kedrion, and CSL Behring. AT reports travel grants to attend scientific meetings from Kedrion, CSL Behring and Baxter. AM reports travel support for attending scientific meetings from CSL Behring—Italy and Kedrion—Italy. RF received personal compensation for serving on the Advisory Board of CSL Behring and Baxter, and travel grants from Baxter, Grifols, Kedrion and CLS Behring. GS received personal compensation for serving on the Advisory Board from Grunenthal, Baxter and Grifols. EN-O reports personal compensation for serving on the Advisory Board of CSL Behring, Baxter, Kedrion and Novartis; he received honoraria for lecturing, and travel grants to attend scientific meetings from Baxter, CSL Behring, Grifols and Kedrion. EP received travel grant to attend scientific meetings from CSL Behring.

  • Patient consent Obtained.

  • Ethics approval The authors declare that they acted in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement DC had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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