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.