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New insights into the management of chronic inflammatory demyelinating polyradiculoneuropathy Yusuf A Rajabally*,1, Patricia H Blomkwist-Markens2 & Hans D Katzberg3

Practice points ●●

As chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a treatable disease, early phenotype recognition is essential.

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The aim of treatment is to improve/maintain functionality and quality of life (QoL).

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Besides disability scales, other outcomes such as grip strength and QoL have the potential to measure treatment response.

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Addressing psychological factors is equally as important as pharmacological treatment in improving QoL in CIDP patients.

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Patient organizations can provide valuable support for patients with CIDP.

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Out-of-hospital infusion strategies for intravenous immunoglobulin (IVIG) are well established in some countries (e.g., the USA and UK) and offer many potential benefits.

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In Canada, a pilot study demonstrated the safety and patient acceptance of home-based IVIG for treatment of CIDP, but logistical issues emerged.

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Infusion pods or self-infused subcutaneous immunoglobulin may be practical alternatives to home-based IVIG therapy.

Summary Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and its variants can be challenging to diagnose and treat. A combination of clinical, electrophysiological and laboratory features is often required to reach a diagnosis. New data are emerging about potential biomarkers and factors that may indicate treatment needs in individual patients. High-quality evidence exists for the efficacy of intravenous immunoglobulin (IVIG) in the treatment of CIDP, including quality of life (QoL) benefits. Besides pharmacological treatment, psychological factors must also be addressed to improve patients’ QoL. Home-based IVIG infusion therapy is currently a well-established approach in some countries. A 6-month pilot study conducted in Ontario, Canada, provided proof of safety and patient acceptance of home-based IVIG therapy, although some logistical issues emerged.

Regional Neuromuscular Clinic, Queen Elizabeth Neuroscience Centre, University Hospitals of Birmingham, Birmingham, B15 2TH, UK GBS/CIDP Foundation International, Narberth, PA 19072, USA 3 Neuromuscular Medicine, University of Toronto, Toronto General Hospital/UHN, Toronto, Canada *Author for correspondence: [email protected] 1 2

10.2217/NMT.15.12 © 2015 Future Medicine Ltd

Neurodegener. Dis. Manag. (2015) 5(3), 257–268

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ISSN 1758-2024

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Review  Rajabally, Blomkwist-Markens & Katzberg Keywords 

• chronic inflammatory

demyelinating polyradiculoneuropathy • CIDP review • home-based treatment • intravenous immunoglobulin • IVIG therapy • quality of life

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired immune-mediated inflammatory disorder of the peripheral nervous system, best described as a spectrum of diseases with numerous variants and a variety of clinical presentations [1–4] . As CIDP is a treatable disease, early phenotype recognition is essential. Several topical issues in the management of CIDP were examined at a scientific event held on 14 July 2014 in Düsseldorf, Germany, organized by Grifols with participation of the GuillainBarré syndrome (GBS)/CIDP Foundation International; the current review is a summary of that event. The article begins with a brief overview of criteria used to diagnose CIDP and examines the evidence for markers of treatment response beyond disability scales. This is followed by a look at the patient perspective on factors that can influence health-related quality of life (QoL) in patients with CIDP. Lastly, the requirements and feasibility of out-of-hospital intravenous immunoglobulin (IVIG) treatment are explored and the results of a pilot study which investigated the safety and feasibility of home-based IVIG therapy for CIDP in Ontario, Canada, are revisited. Diagnosis of CIDP & markers of treatment response Although CIDP is the most common autoimmune neuropathy, its prevalence is low compared with other autoimmune neurological disorders and is criteria-dependent. According to European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) criteria [3] , the prevalence is around 3–5/100,000 and has a male predominance [4] . The estimated incidence of CIDP is about 0.5/100,000 per year and increases with advancing age [2] . The actual incidence is likely to be somewhat higher, however, due to the heterogeneity of presenting features and lack of biological markers to assist in diagnosis [1] . Typical CIDP is characterized by symmetrical proximal and distal muscle weakness, with altered sensation and hyporeflexia or areflexia  [2,3] . The clinical course is steadily or stepwise progressive over a period of 2 months or more or may be relapsing-remitting over a longer period of time [2,3] . A small proportion of patients present an acute onset CIDP resembling GBS which must be discriminated from acute inflammatory demyelinating neuropathy

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in order to optimize treatment [3] ; neurophysiological [5] and neuroimmunological [6] findings may assist in the differential diagnosis of these variants. Atypical CIDP has variable manifestations. Some anatomical forms of CIDP are distal acquired demyelinating symmetric (DADS) neuropathy and multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy also known as ‘Lewis–Sumner syndrome’ [2,3] . Other atypical forms of CIDP depend on the type of nerve fiber involved and may be pure motor or pure sensory (large fiber, small fiber or of the sensory roots as in the entity described as ‘chronic immune sensory polyradiculopathy’) [2,3] . CIDP can occur concurrently with a wide range of other systemic disorders although the exact relationship of the underlying condition to the development of CIDP is uncertain [2] . Indeed, the long-held concept that CIDP occurs more frequently in patients with diabetes mellitus is currently under challenge [7,8] as is the direct link between CIDP and various other systemic diseases. ●●Diagnosis of CIDP

CIDP is diagnosed on clinical grounds and generally in conjunction with electrophysiology  [3] . Electrophysiological features indicative of CIDP include: decrease in motor nerve conduction velocity; prolonged distal motor latency; increased or absent F-waves; conduction block and abnormal temporal dispersion (distal and/or proximal)  [3] . Exhaustive upper limb or fourlimb testing is more sensitive than unilateral or lower limb studies to establish an electrophysiological diagnosis [9] . Evaluation of cerebrospinal fluid (CSF) is a sensitive measure to support a CIDP diagnosis as protein is elevated in approximately 75% of cases. Other supporting investigations include gadolinium-enhanced magnetic resonance imaging (short tau inversion recovery [STIR] or T2 sequences) of the brachial plexus or spinal nerve roots demonstrating hypertrophy and hyperintensity [3] . Nerve biopsy is rarely required to diagnose CIDP as the pathological features are not particularly sensitive or specific (i.e., positive findings are not specific for CIDP and negative findings do not exclude the diagnosis  [3]), although biopsy with electron (or light) microscopy and teased fiber preparations may be useful in carefully selected cases (e.g., macro­ phage-associated demyelination, onion-bulbs, demyelinated/remyelinated fibers, endoneurial

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Insights into management of CIDP  edema and inflammatory infiltrates) and in patients who do not fulfil other basic criteria or who have not responded to initial trials of treatment [2] . Many sets of diagnostic criteria for CIDP have been proposed over the years but, at present, no gold standard exists for diagnosis. The criteria are all complex and vary in terms of electrophysiological features such as number of nerves with demyelination, degrees of abnormalities to define demyelination and number of parameters involved. For purposes of identifying patients who may benefit from treatment, the EFNS/PNS 2010 criteria appear to be the most relevant [10–12] . ●●Treatment of CIDP

The primary aim of CIDP treatment is to improve or maintain patients’ functionality (strength and motor performance) and QoL. The three main types of treatment are IVIG, corticosteroids and plasma exchange [1–4] . The responder rate to first-line treatment is approximately 70%, increasing to 80% if patients who switch to other therapies are also included [13] . The efficacy of IVIG for treatment of CIDP was confirmed in a Cochrane Review which included eight randomized controlled trials (RCTs) involving 332 participants in total [14] . In these studies, IVIG was compared with placebo and other active treatments for CIDP. The studies were homogenous and the risk of bias was considered to be low. In placebo-controlled studies involving 235 patients, a significantly greater proportion of participants showed improvement in disability (on differing scales) within 1 month of IVIG treatment compared with placebo (risk ratio [RR]: 2.40; 95% CI: 1.72–3.36; highquality evidence). The number needed to treat for an additional beneficial outcome was 3.03 (95% CI: 2.33–4.55; high-quality evidence). In three of the eight studies involving 84 participants in total, disability scores were transformed to the Modified Rankin score for better comparability. Using this approach, the improvement of one point with IVIG versus placebo (RR: 2.40; 95% CI: 0.98–5.83) just reached statistical significance and the evidence quality was considered to be moderate. With the participation of 33 centers in 10 countries, the IVIG in CIDP Efficacy (ICE) study demonstrated the long-term benefits of IVIG for treatment of CIDP [15] . In this randomized, double-blind, response-conditional,

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crossover study, 117 patients received 10% caprylate-chromatography purified immunoglobulin intravenous (IVIG) or placebo every 3 weeks for up to 24 weeks. Patients whose inflammatory neuropathy cause and treatment disability (INCAT) score had not improved by at least 1 point by week 6, or improved but then decreased to or below the baseline score at any time at or after week 6, received the alternate treatment in a 24-week crossover period. In either period, patients who showed improvement and completed 24 weeks of treatment were eligible to be randomly reassigned to IVIG or placebo in a 24-week extension phase. During the first treatment period, a greater proportion of patients treated with IVIG than placebo (54 vs 21%) had at least a 1-point improvement in the adjusted INCAT score that was maintained through to week 24, representing a 33.5% difference (95% CI: 15.4–51.7; p = 0.0002). Similar results observed for patients who had crossed over to the alternate treatment validated the first period results. In the extension phase, the probability of relapse was significantly lower in patients who continued to receive IVIG compared with those who had been assigned to placebo (13 vs 45%; hazard ratio 0.19; 95% CI: 0.05–0.70). Approximately one third of CIDP patients are ultimately either refractory or insufficiently responsive to first-line treatments [13] . Some alternative approaches under investigation in this setting include corticosteroid-sparing and IVIG-sparing agents, stem cell transplantation and biological agents that target specific molecules involved in the immunopathology of CIDP  [2,16,17] . Available evidence for azathioprine, interferon and methotrexate indicates little to no benefit with these agents in refractory CIDP  [16,17] . Considerable benefits with cyclophosphamide  [18,19] and cyclosporine [20] were reported in small case series of patients with refractory CIDP, but the lack of new data in the past decade suggests that other research avenues are preferred. Autologous hematopoietic stem cell transplantation induced long-term drug-free remission in 8 of 11 patients with therapy-refractory CIDP [21] , but application of the procedure is limited by the risk of associated infections. Numerous biological agents directed against T cells, B cells and transmigration and transduction molecules (e.g., alemtuzumab, eculizumab, etanercept, fingolimod, natalizumab, rituximab and tacrolimus) have been investigated, with

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Review  Rajabally, Blomkwist-Markens & Katzberg varying degrees of success [2,16–17] . Of note, a retrospective, observational and multicenter study reported a favorable response to rituximab in 9 of 13 patients refractory to conventional therapies for CIDP [22] . Although the targeting of specific antigens points to the possibility of individualizing therapy in future, it is necessary first to confirm the validity and efficacy/safety of these alternative approaches in large, r­a ndomized studies. ●●Markers of treatment response in CIDP

In Europe and elsewhere, response to treatment for CIDP is most commonly measured using disability scales although impairment scales are also used. Other methods used as secondary outcomes to evaluate treatment response in clinical studies include dynamometry, QoL measures and electrophysiology. An important observation from the ICE study was that grip strength measurement (Martin Vigorimeter) captured significantly more improvement in patients treated with IVIG than in those treated with placebo [15] . On this basis, a systematic analysis was undertaken to determine the sensitivity of grip strength as an indicator of meaningful clinical changes [23] . Investigators compared the responsiveness of grip strength and INCAT disability scores measured at each patient visit throughout the study. To assess the proportion of responders to IVIG versus placebo, a minimum clinically important difference cutoff value of greater than 8 kPa for grip strength and greater than 1 point for the INCAT score was applied. Myometry was found to be both reliable and sensitive for identification of treatment response. Grip strength indicated significant improvement sooner than the INCAT disability scale in patients receiving IVIG compared with placebo, as early as day 16 after treatment. In a smaller study involving 11 patients on IVIG maintenance therapy, a clear increase in the strength of various muscle groups as measured with isokinetic dynamometry was observed following reinitiation of IVIG therapy after a short-term withdrawal [24] . Response was maximal between days 5 and 10 after the course of IVIG therapy, with no further improvement beyond day 15. QoL has also been examined as a means to monitor response to IVIG treatment. In the ICE study, clear improvement in the physical and mental component summary scores of the Short Form (SF)-36 Health Survey was observed

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in patients treated with IVIG compared with placebo  [25] . Improvements in favor of IVIG were noted in all eight domains of the SF-36 and reached statistical significance for physical functioning, role–physical, social functioning and mental health. During the extension phase of the study, SF-36 improvements either increased or were maintained in the group who continued IVIG therapy, and worsened in the group reassigned to placebo. These same investigators subsequently explored the relationship between CIDP impairment, activity and participation restrictions, and QoL by investigating the association between scales representing these outcomes  [26] . Disability was best explained by grip strength, INCAT sensory sum score and Medical Research Council (MRC) sum score. In contrast, only up to half the variance in SF-36 physical and mental component summary scores could be explained by CIDP impairment and measures of activity and participation, suggesting that factors other than functional improvement contribute to overall health-related QoL in CIDP patients treated with IVIG. The utility of electrophysiology as a marker of treatment response has also been explored. A subanalysis of the ICE study found significantly greater improvement from baseline in favor of IVIG over placebo for averaged motor amplitudes from all motor nerves (treatment difference 0.62 mV; 95% CI: 0.05–1.20; p = 0.035) and conduction block (treatment difference -5.54%; 95% CI: -10.43 to -0.64; p = 0.027) [27] . These investigators also examined correlations between the changes observed in nerve conduction studies and response to treatment [28] . Motor nerve conduction results and clinical measures were assessed at baseline and at end point/week 24 of the ICE study. Improvement from baseline in the adjusted INCAT score correlated with improvement in proximally evoked compound muscle action potential (CMAP) amplitudes (r = -0.53; p < 0.001) of all nerves tested and with improvement in CMAP amplitude of the most severely affected motor nerve (r = -0.36; p < 0.001). Correlations were also observed between improvements in averaged CMAP amplitudes and dominant-hand grip strength (r = 0.44; p < 0.001) and the MRC sum score (r = 0.38; p < 0.001). While the results suggested that electrophysiology is a useful measure of the clinical response to treatment, the rigorous electrophysiological methodology and strict protocol employed in the ICE study are unlikely

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Insights into management of CIDP  to be a true reflection of neurophysiological practice in most laboratories worldwide. At present, electrophysiological measures are not expected to add value over clinical examination alone. IgG levels as a marker of response to IVIG therapy have also been investigated. To determine the variability of serum IgG in CIDP patients, a group from The Netherlands evaluated serum IgG levels pre- and post-treatment (5 min after infusion) with IVIG in 25 patients with active but stable CIDP [29] . The IVIG level correlated with BMI, lean bodyweight, INCAT disability scores and treatment frequency. Initially, however, the sole correlation described was between the infused dose of IVIG and the increase in serum IgG shortly after infusion (i.e., ΔIgG). The analysis otherwise revealed steady levels of IgG postinfusion suggestive of low interpatient variability which led the authors to conclude that constant levels of IgG are required to reach a steady state in patients with CIDP. With the aim of establishing optimum treatment regimens for individuals with CIDP, Rajabally’s group from the UK correlated IgG levels in patients (n = 15) measured before and 14 days after IVIG treatment with various clinical parameters [30] . No correlations were found between variations in IgG level and body weight, BMI, best clinical response, total dose of IVIG administered or dose of IVIG administered per kilogram per week. However, a significant correlation was identified between ΔIgG at 2 weeks (i.e., mean rise in the IgG level from baseline) and the interval between infusions (p = 0.001); in other words, the higher the IgG level at 2 weeks, the greater the time between infusions. This was an interesting finding in a small series of patients as it suggested significant interpatient variability in IgG metabolism independent of parameters such as dose, BMI or degree of functional improvement. The patient-specific postinfusion rise in IgG levels at the clinically relevant timepoint of 2 weeks may explain differences among patients in treatment frequency needs. Further investigation is warranted to confirm the utility of IgG levels as a predictor of treatment needs in a condition where subjective factors considerably impair the objective evaluation of treatment effects and needs. ●●Monitoring response to CIDP treatment in

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Looking ahead, it is expected that functional scales will continue to be the main method

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of monitoring treatment response in patients with CIDP as they are validated and evidencebased, but may be supplemented by patientrelevant disease-specific measures of disability such as the Rasch-built Overall Disability Scale and the Overall Neuropathy Limitations Scale  [31] . The importance of QoL measures as an outcome in multisymptomatic chronic diseases is increasingly being recognized given the value of feedback from the patient’s own perspective. Grip dynamometry provides an indication of both function and strength and is a highly practical measure of treatment response. The utility of myometry is less clear as it is difficult to gauge the clinical relevance of small changes in isokinetic dynamometry. Electrophysiology is unlikely to find a role in monitoring treatment response due to the high degree of variation in methods/techniques used. Measuring IgG levels to determine treatment response is an interesting concept but of uncertain utility due to the limited data pool, consisting of only 40 patients at present. However, further investigations in this area are either underway or planned by Dutch and UK investigators. Quality of life & voice of the CIDP patient CIDP is a relatively rare condition and its impact on patients’ QoL has not been widely studied [32] . Numerous factors can negatively influence QoL in CIDP patients, from the time before a diagnosis is established through to t­reatment and treatment withdrawal. ●●Impact on QoL

CIDP patients generally present with variable nonspecific symptoms  [33] which can delay diagnosis. By the time patients are referred to a specialist they may be deeply concerned about the cause of their symptoms and ‘desperate’ for a diagnosis. To some patients, receiving a diagnosis of CIDP can come as a relief but, in reality, it simply signals the beginning of another stressful journey. Some of the many challenges patients face at the time of diagnosis include coming to terms with having a disease for the ‘rest of their lives’ and being responsible for deciding the best treatment strategy despite limited or no prior knowledge about the condition. At the same time, patients are trying to cope with weakness, chronic pain, depression, fatigue and anxiety, and dealing with other life issues such as changing roles and

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Review  Rajabally, Blomkwist-Markens & Katzberg relationships, possible job losses and potential insurance issues. CIDP and similar diseases have been shown to affect all QoL domains, with symptoms such as fatigue (65% of patients), pain (39%), mobility (38%) and sleep disturbances (26%) being the most common contributing factors [34] . There are numerous psychosocial factors also to consider. Patients with CIDP must schedule their lives around treatment which may be highly inconvenient at best and serves as a constant reminder about their condition. Patients who are immunosuppressed must be constantly vigilant of illness amongst their family members, friends and work colleagues, maintain a safe distance from people who are sick, and regularly employ infection control techniques (e.g., use of hand sanitizer). These factors all contribute to overall stress and impair health-related QoL in in­dividuals whose self-esteem may already be fragile. Healthy people are able to enjoy life, feel good ‘inside and out’ and have a positive attitude. Good health makes it easier to take decisions, seek opportunities, handle difficult circumstances, manage relationships, and cope with new experiences. In contrast, persons with CIDP or similar conditions have a different starting position. While perhaps not appearing any different on the surface, inwardly patients with CIDP may be dealing with pain, fatigue, depression, frustration and anger. Such a ‘cocktail’ of symptoms and emotions can diminish confidence and impair concentration which, in turn, can give rise to serious issues at the r­elationship, workplace and financial level. The pain associated with CIDP is often highly debilitating. Neuropathic pain, in particular, can be difficult to manage. Moreover, the side effects of pain medications often create new problems while attempting to solve others. Fatigue in neuromuscular disorders continues to be a neglected area of research and its effect on patients’ daily lives is often underestimated. CIDP-associated fatigue goes beyond simple tiredness; its peripheral neuropathic origin causes a type of total physical and mental exhaustion that prevents a person from functioning until completely rested. Similar to pain, fatigue impacts on everyday functioning, concentration and mental well-being. Patients with severe fatigue must learn how to pace themselves in order to conserve energy for priority tasks. For instance, while it may be possible to summon up enough energy to get through a working

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day, there will be none left over to make dinner, socialize or spend quality time with family. Although exercise has been shown to diminish fatigue in CIDP [35,36] , patients who are tired and in pain – and already struggling to juggle their day-to-day activities – may find it difficult to follow recommendations to exercise. Thus, when evaluating patients with CIDP and related diseases, physicians must take into account the full range of factors that constitute an individual’s experience of their condition and the many ways in which CIDP can impact on patients’ QoL. ●●Treatment & support

First-line treatments for CIDP include IVIG, corticosteroids and plasmapheresis [1–4,33] . As each case of CIDP differs, treatment must be individualized. To facilitate a tailored approach, it is important to listen carefully to the patient. Although some markers of disease can be measured objectively, the patient generally has the best idea of how he/she is ‘doing’ relative to last week, last visit or last year. In choosing a treatment strategy, its possible impact on the patient’s long-term health should be considered. Relapse prevention is central to the effective management of CIDP as each relapse increases the chances of permanent damage. Identifying the right combination of drug and treatment frequency is arguably the most challenging aspect of CIDP management – a ‘o­ne-size-fits-all’ approach does not work. Long-term IVIG treatment has been associated with improvements in both the physical and psychosocial aspects of health-related QoL in CIDP patients [25] . Corticosteroids are also an effective treatment option but their ‘bad reputation’ (e.g., from magazines, websites) often makes it difficult for physicians to convince patients of their usefulness. Given the known risks of long-term corticosteroid therapy, a treatment and monitoring plan must be devised in collaboration with the patient and his/her primary care physician [2] . The route and site of drug administration also need to be taken into account. For example, some patients prefer the convenience of home-based IVIG infusions, while others are more comfortable in a hospital setting. Subcutaneous rather than intravenous administration of immunoglobulins may be the most suitable option for some patients. The decision to begin tapering treatment to determine whether discontinuation is feasible

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Insights into management of CIDP  can be a particularly stressful time for CIDP patients due to the fear of relapse. Common approaches to tapering are to decrease the dose or lengthen the interval between doses but, whichever method is used, treatment withdrawal needs to be a mutual decision between patient and physician and both parties must feel comfortable with the decision. Additional information and support for CIDP patients can be found in a variety of sources. The book ‘Coping with Peripheral Neuropathy’ by Scott Berman [37] describes the patient’s perspective of living with CIDP and is recommended reading for patients and physicians alike. Patient groups, such as the GBS/CIDP Foundation International in the USA [38] and the Guillain– Barré & Associated Inflammatory Neuropathies (GAIN) organization in the UK [39] provide materials and support and act as the ‘voice’ of the patient. Both organizations have a focus on patient advocacy as well as on stimulating and financing research. Physicians should make themselves aware of the CIDP resources and organizations in their region and pass along details and recommendations to their CIDP patients. In sum, the effects of CIDP on health-related QoL are multifaceted, ranging from physical symptoms to impairment of daily activities to psychosocial issues [26] ; all factors must be taken into account when managing a patient with CIDP. Although effective pharmacological treatment can improve patients’ health-related QoL, it is equally important to address psychological factors. Patients must be treated on an individual basis and can be referred to patient organizations for additional support. Out-of-hospital immunoglobulin infusion options for patients with CIDP ●●Home IVIG for CIDP: global perspectives

In the US, home-based IVIG therapy for immune deficiency and neuromuscular conditions has been in use for more than two decades and is regarded as a safe approach. A retrospective analysis was reported of 1085 infusions of IVIG administered in the home setting to 70 patients (median age 65 years) with neuro­muscular disease [40] . The range of diseases included CIDP/GBS (n = 46), myasthenia gravis (MG; n = 8), polymyositis (n = 4), dermatomyositis (n = 2) and other conditions (n = 12) including stiff person’s syndrome. The tolerability profile of home-based IVIG in this group was favorable, including in the 23 patients who were IVIG-naïve.

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Although out-of-hospital IVIG infusion is not routinely available throughout the whole of Europe, countries such as The Netherlands and UK have well-established programs in which safe and efficacious treatment of neuromuscular conditions has been demonstrated [41–44] . In the UK, this includes patient self-infusion of IVIG through port catheters, an approach not routinely used elsewhere including in the US. In Denmark, the lack of a home-based IVIG program has led to increasing interest in self-infused subcutaneous immunoglobulin (SCIG) programs, another recently available option for out-of-hospital treatment of CIDP [45,46] . In Canada, the current standard for administration of IVIG is through a day unit at a hospital. No routine out-of-hospital IVIG infusion options exist for treatment of neuromuscular conditions. In Ontario, Canada, the University Health Network (UHN) operates four major hospitals in the greater Toronto metropolitan region that service the entire province (Figure 1) . Due to the vast land mass covered and relative remoteness of some regions, patients with neuromuscular conditions frequently encounter regionality and access issues that can complicate the provision of care. The current model of care for UHN patients who require IVIG but do not live close to the hospitals in Toronto is to liaise with peripheral hospitals in an attempt to have the treatment delivered closer to home. The situation presents challenges in cases where there is no available clinician or neurologist in the local area to prescribe or administer IVIG or where expertise in the administration of IVIG in the local hospital is lacking. In these situations, the UHN may provide education to local hospitals and clinicians about IVIG administration. Otherwise, patients must travel into downtown Toronto which, in many cases, involves extended distances. Many of the challenges inherent with either scenario could be alleviated with the development of a home-based IVIG infusion program. ●●Benefits & challenges of home-based IVIG

therapy for CIDP

Immune-mediated neuropathic conditions such as CIDP often require frequent and prolonged immunomodulatory therapy to maintain patients with minimal burden of disease and disability. However, the increased overall utilization

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Region 1

Region 4

Region 2

Region 5 Region 3

Figure 1. Ontario health regions. The University Health Network operates four major hospitals in Toronto (Region 3) that service the entire province.

of IVIG, coupled with increasingly limited resources at hospital day units where IVIG is administered, complicates patient care under the current model in Canada. Home-based IVIG therapy offers the possibility to simultaneously alleviate pressures on precious hospital resources while optimising treatment for patients. Benefits such as greater patient autonomy over condition and treatment, minimal time spent away from home or work, decreased traveling time and lower associated costs all have the potential to improve patients’ QoL, which is a major goal when treating CIDP and other chronic medical conditions. That said, there are occasions where patients may prefer hospital-based therapy. Older patients, in particular, often prefer receiving IVIG treatment in hospital for the peace of mind and social interaction. Patients frequently interact and inform each other during the infusions. In day units or

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wards, patients are closely monitored during the infusion for adverse events and the physician is generally nearby or can be contacted in the event of any questions or issues. While several benefits are perceived with the implementation of home-based IVIG therapy for patients with neuromuscular disorders (Box 1) , there are also a number of prerequisites. A system must be in place for managing common side effects (headache, fever and site reactions) as well as potentially paroxysmal events such as hemolysis, renal toxicity, cardiovascular events and severe allergic reactions. Communication systems with the blood bank must be in place to ensure proper documentation and tracking of administered IVIG lot numbers. Training programs for specialized nurses must be established. Consistent and safe protocols must be implemented that are specific to patients with

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Insights into management of CIDP 

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Box 1. Perceived benefits of out-of-hospital intravenous immunoglobulin therapy. ●●

Potential for a positive impact on patients’ quality of life and overall outcomes

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Improvement in patient compliance

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Increased education and interaction with patients’ families regarding treatment for neuromuscular disorders

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Decreased travel times for treatment

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Reduced loss of functionality/worktime for patients

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Opportunity for improved patient care and interprofessional collaborative research and development (blood bank, nursing, physicians)

neuromuscular disorders including patients with specialized needs due to neurological impairments [47] . ●●Home IVIG for CIDP study: new evidence

The search for alternatives to hospital-based IVIG therapy for patients with chronic neuromuscular disorders in Ontario, Canada, prompted the design and conduct of a needs assessment/feasibility study, which was followed by a pilot study at the UHN to determine the safety of out-ofhospital IVIG for treatment of CIDP [48] . The pilot study involved ten patients with active but

stable CIDP who had been receiving maintenance IVIG in hospital. The patients were scheduled to receive monthly treatment at home with 10% IVIG for 6 months and were evaluated by study clinicians at baseline, 3 months and study end. Although this was primarily a safety study, several other clinical parameters were assessed at baseline and 6 months to ensure that the patient’s condition remained stable throughout the study (Figure 2) . Primary outcomes were adverse events, health utility index and QoL. Additional data collected included INCAT disability scores, MRC sum score, grip strength and a patient

Baseline assessments

10 CIDP patients requiring monthly IVIG infusion

6-month assessments

1) Primary outcome a) Adverse events b) Health utility index c) Quality of life

2) Additional data collected: a) NCS/EMG b) INCAT c) MRC sum score d) Grip strength e) Patient preference questionnaire

3-month interim assessment

Return to monthly hospital IVIG treatments if disease stability not maintained

1) Primary outcome a) Adverse events b) Health utility index c) Quality of life

2) Additional data collected: a) NCS/EMG b) INCAT c) MRC sum score d) Grip strength e) Patient preference questionnaire

Monthly therapy with home-based IVIG

Figure 2. Home-based IVIG infusion therapy: study design. CIDP: Chronic inflammatory demyelinating polyradiculoneuropathy; INCAT: Inflammatory neuropathy cause and treatment disability; IVIG: Intravenous immunoglobulin; MRC: Medical research council; NCS/EMG: Nerve conduction studies/electromyogram. Data taken from [48].

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Review  Rajabally, Blomkwist-Markens & Katzberg preference questionnaire. A dedicated study nurse collected product from the blood bank (1–2 g/kg over 1–2 days every 3–4 weeks as per the subjects’ typical infusion schedule) and traveled to patients’ homes to administer the IVIG. Ten patients (six male) were enrolled in the study from September to December 2011. The age range was 26–80 years and all patients had previously been treated with IVIG. As reflects usual clinical practice, there was considerable variation among patients in terms of their cl­inical presentation and disease severity (Table 1) . No serious reactions related to IVIG occurred. Nine patients received complete IVIG infusions over 6 months. Occurrences of anticipated postinfusion events such as headache and fatigue were managed with analgesics and supportive counseling. One patient experienced a ‘flare’ of CIDP symptoms near the end of the study and required follow-up in the clinic. Nine of the ten patients expressed a preference for home treatment. All patients expressed satisfaction with the individualized quality of therapy, as well as the increased autonomy in managing their own health and the minimization of difficult commutes and time spent in a medical day care unit. In all patients, the INCAT disability score either remained stable (varied by

New insights into the management of chronic inflammatory demyelinating polyradiculoneuropathy.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and its variants can be challenging to diagnose and treat. A combination of clinical,...
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