Introduction
Multifocal motor neuropathy (MMN) and chronic inflammatory demyelinating polyneuropathy (CIDP) are chronic, immune-mediated disorders that affect the peripheral nerves, leading to progressive muscle weakness and, in the case of CIDP, sensory disturbances. Reference Bunschoten, Jacobs, Van den Bergh, Cornblath and van Doorn1,Reference Yeh, Dyck, van den Berg, Kiernan and Taylor2 These conditions are debilitating and often require long-term management to prevent disease progression and maintain functional abilities. Intravenous immunoglobulin (IVIG) therapy has long been the cornerstone of treatment for both MMN and CIDP, providing a means to modulate the immune response and stabilize or improve neurological function. IVIG administration typically requires regular hospital visits for infusions, which can be burdensome for patients and impact on their quality of life (QoL). Reference Katzberg, Rasutis and Bril3 In recent years, subcutaneous immunoglobulin (SCIG) has emerged as a viable alternative, offering the potential for self-administration at home, thus enhancing patient autonomy and reducing the frequency of hospital visits. Reference Markvardsen and Harbo4 SCIG is gaining recognition not only for its efficacy, which is comparable to that of IVIG, but also for its safety profile, with studies suggesting a lower incidence of systemic adverse effects.
QoL is a critical outcome in the management of chronic diseases like MMN and CIDP, as it encompasses the overall well-being and daily functioning of patients. Given the chronic nature of these conditions, where patients often undergo treatment for many years, the impact of therapy on QoL is of paramount importance. Reference Mahdi-Rogers, McCrone and Hughes5,Reference Hadden and Marreno6 Despite the increasing adoption of SCIG, there has been a paucity of comprehensive data directly comparing the QoL outcomes between SCIG and IVIG therapies. While several studies have explored the clinical efficacy of these treatments, fewer have systematically examined how they affect QoL, particularly from the patient’s perspective. The existing studies often vary in their design, duration and the specific QoL instruments used. Reference Lins and Carvalho7–Reference Garratt, Engen and Kjeldberg10 These differences make it challenging to aggregate results and draw definitive conclusions about the relative impact of SCIG versus IVIG on QoL. Furthermore, some QoL instruments may not fully capture the unique challenges faced by patients with neuropathic conditions, adding another layer of complexity to the interpretation of these outcomes.
The current study seeks to address these gaps by conducting a review and analysis of existing literature on the QoL outcomes associated with SCIG treatments in patients with MMN and CIDP, including those who have transitioned from IVIG. By focusing on studies that utilize validated QoL instruments, this review aims to provide a better understanding of how these treatment modalities influence patient well-being. The goal is to determine whether SCIG can offer comparable or potentially superior QoL outcomes compared to IVIG, thereby providing evidence-based insights that can guide clinicians in optimizing treatment strategies for these patients. This study also seeks to highlight the broader implications of treatment choice on daily living, patient satisfaction and long-term health-related QoL in this patient population.
Methods
We conducted a comprehensive search of PubMed for studies that measured QoL outcomes in MMN and CIDP patients receiving SCIG and IVIG between 2009 and 2024. Change in QoL scores as measured by validated tools compared with baseline values collected during IVIG treatment. Secondary outcomes included adverse effects, treatment satisfaction and functional status of patients during treatment with SCIG. We included all the studies that measure the QoL in CIDP and MMN patients who received SCIG and, when available, compared this to the IVIG treatment period. Review papers, case reports, mixed method approaches and economic evaluations not relating to QoL were excluded from the study. Papers assessing the impact of facilitated SCIG were also excluded.
Measures used to assess the QoL in these studies included the Short Form 36-item Health Survey (SF-36), Reference Lins and Carvalho7 health-related QoL Treatment Satisfaction Questionnaire for Medicine (TSQM), Reference Vermersch, Hobart, Dive-Pouletty, Bozzi, Hass and Coyle8 Chronic Acquired Polyneuropathy Patient-Reported Index (CAP-PRI), Reference Bjelica, Peric and Gwathmey9 EuroQoL 5-Dimension (EQ-5D) Reference Garratt, Engen and Kjeldberg10 and Health Utility Index Quality of Life score (HUI-QoL), Reference Horsman, Furlong, Feeny and Torrance11 and the work-related impact was assessed with the Work Productivity and Activity Impairment Questionnaire for General Health (WPAI-GH). Reference Anis12 Specifics related to each outcome measure are detailed in Table 1.
Table 1. Description of quality-of-life measures
Results
The results of this review include data from 13 studies evaluating the QoL outcomes in patients with MMN and CIDP treated with SCIG, compared to those treated with IVIG. In total, 71 MMN patients and 349 CIDP patients were included, with study durations ranging from 3 months to 7 years. Details on these studies including the study specifics, methodology and outcomes are outlined in Table 2 and summarized below.
Table 2. Description and results from included SCIG studies
SCIG = subcutaneous immunoglobulin; QoL = quality of life; MMN = multifocal motor neuropathy; CIDP = chronic inflammatory demyelinating polyneuropathy; SF-36 = Short Form 36-item Health Survey; LQI = Life Quality Index; MRC = Medical Research Council sum score; HRQL = health-related quality of life; VAS = Visual Analog Scale; ONLS = Overall Neuropathy Limitations Scale; HUI-QoL = Health Utility Index Quality of Life score; RODS = Rasch-built Overall Disability Scale; INCAT = Inflammatory Neuropathy Cause and Treatment; EQ-5D-5L = 5-level EuroQoL 5-Dimension; ODSS = Overall Disability Sum Score; TSQM = Treatment Satisfaction Questionnaire for Medicine; WPAI-GH = Work Productivity and Activity Impairment – General Health; CAP-PRI = Chronic Acquired Polyneuropathy Patient-Reported Index; 40 MWT = 40 m walk test; 6-SST = 6-spot step test.
CIDP studies
In CIDP patients, the studies collectively indicate a positive impact of SCIG on QoL. Reference Horsman, Furlong, Feeny and Torrance11,Reference Hartung, Mallick and Bril14-Reference Cocito, Peci, Romagnolo and Sci17,Reference Harbo, Andersen, Hess, Hansen, Sindrup and Jakobsen20 Cirillo et al. followed 14 CIDP patients who initially responded to IVIG and were switched to long-term SCIG and followed for up to 48 months. QoL, assessed using the EuroQoL Visual Analog Scale, significantly improved after the switch: from a baseline of 51.5 ± 8.1 to 69.4 ± 8.4 at 24 months (P = .016) and further to 86.0 ± 7.5 at 48 months (P = .00031). These results indicate a sustained and progressive improvement in QoL following the transition from IVIG to SCIG. Reference Cirillo, Todisco, Ricciardi and Tedeschi13 Hartung et al. evaluated patients with CIDP who were stabilized on IVIG and then randomized to receive SCIG or placebo. After 24 weeks, a higher proportion of SCIG-treated patients maintained or improved their QoL. In the “usual activities” domain of the EQ-5D, 90.6% of those receiving 0.4 g/kg SCIG improved or maintained status versus 68.2% on placebo (P = 0.006). Sensitivity analyses also demonstrated significant benefits in mobility (P = 0.002) and pain/discomfort (P = 0.003), suggesting that SCIG helped preserve or slightly enhance QoL after switching from IVIG. Interpretation of these findings, however, requires caution: in the placebo arm, 32 of 57 participants relapsed and received rescue IVIG within about 1 week of relapse detection, which may have diminished observed between-group differences. As a result, the PATH trial reflects a comparison of SCIG with placebo plus frequent rescue IVIG, rather than SCIG versus no immunoglobulin therapy. Reference Hartung, Mallick and Bril14
Gentile et al. performed a long-term observational study of 17 CIDP patients, followed for up to 84 months after switching from IVIG to SCIG. Using the Life Quality Index (LQI), which were assessed at baseline (T0) -right before switch IVIG to SCIG- and at follow-up (T1), which could be up to 84 months, the study found that patients experienced stable or improved QoL, with notable enhancements in walking ability and overall daily living activities. Reference Gentile, Mazzeo, Russo, Arimatea, Vita and Toscano15 Cocito et al. conducted a study in 2013 with 10 CIDP patients, reporting significant LQI improvements after patients switched to a higher concentration of SCIG (20%) and reduced infusion frequency from a lower concentration SCIG formulation. Reference Cocito, Paolasso, Peci, Spagone and Lopiano16 Similarly, Cocito et al. in 2017 studied seven CIDP patients who switched to SCIG “bolus” administration, finding significant improvements in LQI subdomains related to daily living activities and therapy-related problems, indicating a better QoL overall post-switch. Reference Cocito, Peci, Romagnolo and Sci17 Vu et al. examined 15 CIDP patients, who were dependent on IVIG for disease control, using SF-36, TSQM and CAP-PRI tools, and found significant improvements in specific QoL domains, including physical role limitations and treatment satisfaction, following the switch to SCIG. Reference Vu, Anthony and Alsina18
MMN studies
MMN patients also showed stable or improved QoL outcomes following the switch from IVIG to SCIG. Katzberg et al. studied 15 MMN patients over 6 months, assessing QoL with the Health Utility Index (HUI-QoL). The study found that QoL scores were unchanged for the duration of the study after making the switch from IVIG to SCIG, with patients reporting high levels of satisfaction with SCIG therapy. A dosing ratio of 1.53:1 conversion from IVIG to SCIG was necessary to maintain strength and serum IgG levels, with underdosing linked to clinical deterioration. Primary reasons for patients’ satisfaction included the convenience and lower side effect profile of SCIG compared to IVIG. Although generally well tolerated, systemic adverse events such as elevated transaminases were noted, necessitating vigilant patient monitoring during the transition phase. Reference Katzberg, Rasutis and Bril19 Harbo et al. conducted a smaller study involving nine MMN patients treated with SCIG and IVIG in a crossover design. The study, using the SF-36 tool, found no significant differences in QoL between the two treatments, suggesting that SCIG was as effective as IVIG in maintaining QoL. Reference Harbo, Andersen, Hess, Hansen, Sindrup and Jakobsen20
Eftimov et al. explored QoL in 10 MMN patients who transitioned from IVIG to SCIG. The study used SF-36 and LQI as QoL measures, finding that patients who received SCIG at a dose equivalent to 100% of their previous IVIG dose maintained muscle strength and QoL. Reference Eftimov, Vermeulen, de Haan, van den Berg and van Schaik21 Misbah et al. also reported that among eight MMN patients who switched to SCIG, six showed improvements in LQI scores after 6 months, indicating enhanced QoL despite stable clinical endpoints. Reference Misbah, Baumann and Fazio22 Gentile et al. provided further evidence by following eight MMN patients for up to 96 months post-switch to SCIG, finding improvements in LQI scores, particularly in walking capability, hand function and overall satisfaction. Reference Gentile, Russo and Rodolico23
Combination studies (CIDP and MMN)
Combination studies that included both CIDP and MMN patients provided a broad perspective on QoL outcomes. Cocito et al. conducted a prospective observational study involving 66 CIDP and 21 MMN patients who switched from IVIG to SCIG. Reference Cocito, Merola and Peci24 The study found that QoL, as measured by the LQI, improved in CIDP patients and remained stable in MMN patients. Additionally, the study reported that patients from both groups perceived an improvement in their therapeutic environment and daily activities after switching to SCIG.
The studies highlighted important advantages of SCIG over IVIG, particularly regarding self-administration and reduced systemic adverse effects. Gentile et al. (2021) demonstrated that long-term SCIG in MMN allowed home-based self-infusion with sustained motor stability and improved LQI, especially in reducing hospital visits and IVIG-related adverse effects like hemolytic anemia. Reference Gentile, Russo and Rodolico23 Similarly, Gentile et al. (2020) showed that in CIDP, patients preferred SCIG due to its flexibility, fewer systemic side effects and improved satisfaction in areas such as treatment interference and setting. Reference Gentile, Mazzeo, Russo, Arimatea, Vita and Toscano15 Cirillo et al. (2018) confirmed long-term clinical and neurophysiological benefits of SCIG in CIDP, along with a lower rate of systemic reactions. Reference Cirillo, Todisco, Ricciardi and Tedeschi13 Cocito et al. (2013) found that switching to a higher concentration SCIG (20%) reduced infusion frequency and significantly enhanced treatment convenience without compromising efficacy. Reference Cocito, Paolasso, Peci, Spagone and Lopiano16 Lastly, Katzberg et al. (2016) reported high patient satisfaction with SCIG in MMN, citing better tolerability, stable strength and more consistent serum IgG levels compared to IVIG. Reference Katzberg, Rasutis and Bril19
Discussion
The current study reviews the QoL outcomes and patient satisfaction in patients with MMN and CIDP treated with SCIG and aims to compare this to conventional treatment with IVIG. Although there were studies with a larger number of patients with active disease and a spectrum of higher disease severity, many of the earlier pilot studies included smaller groups of patients with variable dosing strategies. In addition, the QoL measures used also varied widely among studies, all factors making direct comparison of the studies a challenge. Within these limitations, the current review highlights that SCIG offers, at a minimum, comparable QoL outcomes to IVIG, with additional benefits in self-administration, reduced systemic adverse effects and enhanced patient satisfaction. These findings align with previous studies that have established the efficacy of SCIG in various immune-mediated neuropathies.
Although the majority of studies examined showed stability in QoL after making a change from IVIG to SCIG treatment, some studies identified an actual improvement in certain QoL measures after switching therapies. These domains primarily involved items such as physical role limitations, interference of treatment in daily activities, patients’ perceptions of their treatment setting and therapy-related problems, which can be explained by the convenience of home administration and reduced travel to medical facilities. Among the scales, the LQI was able to most consistently identify health-related QoL improvements, in addition to maintenance of muscle strength and disability in patients receiving SCIG. Reference Cirillo, Todisco, Ricciardi and Tedeschi13,Reference Gentile, Mazzeo, Russo, Arimatea, Vita and Toscano15,Reference Cocito, Paolasso, Peci, Spagone and Lopiano16,Reference Gentile, Russo and Rodolico23 This included six out of eight MMN patients in an open-label proof-of-concept study over 6 months. Reference Misbah, Baumann and Fazio22 Similarly, studies from Cocito et al. evaluating CIDP patients transitioning from IVIG to SCIG, including “bolus” SCIG regimens, reported significant improvements in LQI scores, emphasizing that SCIG could provide comparable clinical efficacy to IVIG while offering enhanced QoL due to less frequent dosing and the ability to administer treatments at home. Reference Cocito, Peci, Romagnolo and Sci17,Reference Cocito, Merola and Peci24 In the PATH study, QoL was assessed using the EQ-5D health profile and the VAS. Patients treated with SCIG showed higher proportions of maintained or improved health status in various dimensions compared to placebo. Additionally, the WPAI-GH results indicated less work impairment and greater productivity among SCIG-treated patients, demonstrating substantial benefits in terms of daily work and activity levels. Reference Hartung, Mallick and Bril14
Correlations between QoL and clinical outcomes yield unique insights into the scales used as well as items relevant to patients with immune neuropathies. Ryltoft et al. used the EQ-5D-5L questionnaire and found that while QoL was reduced in SCIG-treated patients compared to healthy controls, it correlated strongly with gait performance and disability, but not with muscle strength. This highlights the importance of managing functional mobility for improvements in patient QoL. Reference Ryltoft, Al-Zuhairy, Sindrup, Andersen and Markvardsen25 As all SCIG studies involved a switch from previously effective IVIG therapy, stability in the primary and secondary efficacy outcomes and avoidance of clinical relapse are study goals. This correlates with the majority of stable QoL measures over the study duration in the reported studies; however, it is difficult to confirm that QoL outcomes may not actually improve with SCIG therapy compared to IVIG as disease-specific QoL measures were not routinely used. The only study in the current review that used a neuropathy-specific QoL measure was Vu et al., who showed improvement in physical role limitations on the CAP-PRI in treated patients, indicating increased satisfaction in CIDP patients treated with SCIG. Reference Vu, Anthony and Alsina18 This highlights the importance of using consistent and neuropathy-specific QoL measures when studying patients with MMN and CIDP and the need for renewed efforts to incorporate inflammatory neuropathy-specific QoL outcome measures in future studies. This could include the inflammatory neuropathy QoL scale, a recently developed questionnaire for CIDP and Guillain–Barré Syndrome, which fulfills clinimetric requirements, correlates with patient self-assessment of QoL and shows treatment responsiveness. Reference Draak, Faber and Merkies26
Dosing played a role in ensuring QoL was maintained throughout the course of SCIG treatment, particularly in early studies still evaluating the adequate equivalent SCIG dose to IVIG needed to maintain stability. Eftimov et al. studied QoL using the SF-36 and LQI in a small group of MMN patients treated with SCIG and found that patients who received 100% equivalent dosing to IVIG maintained muscle strength and reported stable QoL measures, while those who received only 50% of the IVIG dose experienced a decline, necessitating a return to IVIG therapy. Local adverse events such as redness and swelling were common but decreased over time. Reference Eftimov, Vermeulen, de Haan, van den Berg and van Schaik21 This study emphasizes the importance of adequate SCIG dosing of at least 1:1 of the IVIG dose in order to not only maintain muscle strength but also ensure adequate QoL in CIDP and MMN, a point which has been confirmed through multiple subsequent studies. Katzberg et al. evaluated a higher 1.51:1 SCIG:IVIG strategy in patients with MMN Reference Katzberg, Rasutis and Bril19 based on bioavailability studies in immune deficiency, suggesting that a higher SCIG dose was required to generate equivalent serum immunoglobulin levels to IVIG. Reference Berger, Jolles, Orange and Sleasman27 This study found that although most patients reported high satisfaction and were able to maintain muscle strength and HUI-QoL during the 6 months of the study, three patients experienced intolerable weakness leading to study exit. This occurred in patients receiving less than the planned 1.5:1 dosing, highlighting the need for close monitoring in patients with MMN switched to 1:1 SCIG:IVIG dosing and raising the question of whether a higher dose is needed in some patients to maintain stability. In Cocito et al. 2014, patients with CIDP and MMN were shifted from IVIG to SCIG therapy. Regarding SCIG to IVIG dosing, the IVIG doses administered ranged from 1 to 2 g/kg monthly. This was transitioned to an equivalent SCIG dose (using either a 16% or 20% IgG solution). Patients showed a significant improvement in disability scores (Overall Neuropathy Limitations Scale score improved, p = 0.018), while MMN patients remained stable. The stable efficacy is likely due to pharmacokinetic differences: SCIG administration results in more stable serum IgG levels, avoiding the peaks and troughs seen with IVIG (which can cause a “wear-off” effect). Regarding adverse effects, SCIG had a lower incidence of systemic adverse events compared to IVIG, as 21.8% of patients had adverse events with IVIG. On the other hand, only one patient had a significant adverse reaction with SCIG (localized erythema), which resolved with site rotation, and therapy was continued. Reference Cocito, Merola and Peci24
Reversion to IVIG also also addressed in many studies. In patients with CIDP, reversion to IVIG after switching to SCIG was relatively uncommon, typically ranging from 0% up to 20%. The most common reasons included personal preference, lack of perceived benefit, side effects (e.g., neutropenia or skin reactions) and patient withdrawal from studies. For example, Gentile et al. reported 2 out of 17 patients (11.8%) who reverted – one due to dissatisfaction and another despite clinical stability. Reference Bunschoten, Jacobs, Van den Bergh, Cornblath and van Doorn1 Reference Mahdi-Rogers, McCrone and Hughes5 Vu et al. noted a 20% withdrawal rate, though not all returned to IVIG. Reference Vu, Anthony and Alsina18 In contrast, studies like those by Cirillo and Cocito (2013, 2017) and the PATH trial showed no or minimal reversion, especially in well-selected patients with stable disease and appropriate SCIG dosing. Reference Cirillo, Todisco, Ricciardi and Tedeschi13,Reference Hartung, Mallick and Bril14,Reference Cocito, Paolasso, Peci, Spagone and Lopiano16
In MMN patients, reversion rates were generally higher, ranging from 0 to 40% and largely associated with initial underdosing of SCIG or early clinical deterioration. Eftimov et al. reported the highest reversion rate (40%) when SCIG was started at only 50% of the IVIG dose. Reference Eftimov, Vermeulen, de Haan, van den Berg and van Schaik21 Katzberg et al. observed a 20% reversion rate among those on suboptimal dosing (< 1.53:1 ratio). Gentile et al. described temporary IVIG use in 25% of patients for symptom worsening, but SCIG was continued. Reference Katzberg, Rasutis and Bril19 Studies using well-titrated dosing strategies and gradual transition protocols, like Harbo et al., showed no reversion, highlighting the importance of proper patient selection and dose equivalency. Reference Harbo, Andersen, Hess, Hansen, Sindrup and Jakobsen20
In conclusion, the review suggests that SCIG is a viable alternative to IVIG for treating MMN and CIDP, offering comparable clinical efficacy with possible patient improvement in certain aspects of QoL. Future research should aim to standardize QoL assessment tools and include larger, long-term studies to better capture the nuanced benefits of SCIG. Addressing these limitations will strengthen the evidence base and support the broader adoption of SCIG in clinical practice, ultimately improving patient outcomes in immune-mediated neuropathies.
Acknowledgments
The authors have no acknowledgments to report.
Author contributions
All authors have equally contributed to data collection and analysis of the study.
Funding statement
The authors received no financial support for the research, authorship and/or publication of this article.
Competing interests
The authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.
H. Katzberg has been a consultant to, served on data safety monitoring boards and participated in clinical research for the following companies: Octapharma, UCB Pharma, Alnylam, CSL Behring, Alexion, AstraZeneca, Argenx, Takeda, Dianthus, BioCryst, Johnson & Johnson, CIHR, Abcuro and Romtech.
V. Bril has received grants or consultation fees from the following companies: Sanofi, Immunovant, Momenta, UCB Pharma, Alnylam, Argenx, Takeda and Johnson & Johnson.
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