A Delphi consensus on integrating novel therapies into the management of generalized myasthenia gravis

Abstract

Background:

The treatment landscape for myasthenia gravis (MG) has evolved with the introduction of novel therapies. An international consensus on patient selection criteria and optimal time to initiate these therapies could improve clinical outcomes and reduce delays for likely beneficiaries.

Objective:

This Delphi consensus was undertaken by MG specialists from selected European countries to explore gaps in the application of national guidelines and elicit expert opinion in practice.

Design:

A mixed-method approach was used; qualitative and quantitative study phases were combined to explore key concepts and reach consensus.

Methods:

The qualitative first phase involved seven healthcare professionals (HCPs) and two patient advocacy group representatives who participated in idea generation. Findings from this phase supported the development of a Delphi survey, which was completed by 16 HCPs in two rounds. This constituted the quantitative second phase of the study. Consensus was defined as ⩾70% agreement or disagreement on a 6-point Likert scale.

Results:

In total, 65% of statements achieved consensus. Key findings include—HCPs highly regard international guidelines but find critical discrepancies between the “ideal” scenario and current clinical practices. Consensus was achieved on the importance of incorporating patient-related quality of life in decision-making, despite limited current methods. Consensus was obtained on steroid tapering and treatment-switch criteria based on steroid dose and duration. Consensus was also achieved on suitable patient profiles, including those with persistent symptoms, severe side effects, or needing rapid control.

Conclusion:

This study recognized that guidelines offer valuable direction but do not replace individualized treatment decisions. This study identified the areas of alignment and opportunities to refine patient selection criteria and treatment-switch categories, particularly to integrate novel therapy use in MG management, highlighting a path to a more patient-centric approach.

Introduction

Myasthenia gravis (MG) is a rare, autoimmune disease characterized by increased muscle fatiguability. It is caused when autoantibodies (IgG) impair neuromuscular transmission at the postsynaptic membrane of the neuromuscular junction. ¹ As a result, people living with MG face fluctuating muscle weakness and fatigue, which worsen with exertion and improve with rest.^2,3 Often, initial symptoms manifest in ocular muscles, with symptoms progressively generalizing to weakness of axial, bulbar, limb, and respiratory muscles in over 80% of cases, also known as generalized myasthenia gravis (gMG).^4–6

The estimated global prevalence of MG ranges from 150 to 200 cases per million. In Europe, prevalence can range widely between countries, reportedly estimated from 2.19 to 36.71 cases per 100,000 persons.^7–11 Current estimates also report higher prevalence among older populations in Europe. ¹² Over 90% of MG cases are antibody-positive for acetylcholine receptors (AChR), muscle-specific tyrosine kinase (MuSK), or, in rare cases, low-density lipoprotein receptor-related protein 4 (LRP4). ¹⁰

Despite therapeutic advances, no curative treatment exists for MG. ¹³ Traditional symptomatic and disease-modifying therapies are now supplemented by novel agents like complement inhibitors (C5i) and neonatal Fc receptor inhibitors (FcRni), which target downstream immunological mechanisms.^13–15 Yet, many patients face a substantial disease burden, underscoring an unmet need for more effective, individualized options. Primary clinical evidence suggests that novel therapies can provide quick relief, with generally only a mild-to-moderate risk profile, and a potential for reducing exacerbation or crisis.^14,16–21 Emerging real-world evidence (RWE) also suggests steroid-sparing benefits of novel molecular treatments. ²²

Since their introduction, several national guidelines have recognized the importance of including novel therapies, particularly for difficult-to-treat MG patients.^23–26 Despite such progress, patient access to these drugs remains inconsistent, with significant disparities among countries, often driven by regulatory and approval hindrances. ²⁷ Prompted by uncertain cost-effectiveness evidence, policy recommendations underline careful consideration of financial constraints when prescribing C5i or FcRni. ²⁸ Adding to these challenges is the lack of a clear and uniform definition of patient selection criteria and the optimal timing for novel therapy initiation. While the lack of international consensus on optimal treatment sequencing, dose, and duration for these treatments, ¹⁶ may partly reflect the individualistic nature of the disease, it is also compounded by limited long-term safety and efficacy data. ²⁹ Combined, these challenges limit patient access as well as the evaluation of the comparative value of novel treatments in wider populations. ³⁰

Evidence suggests that people living with MG prioritize therapies that offer rapid and sustained treatment effects with minimal side effects, something that novel therapies are touted to offer. ³¹ However, in contrast to this ideal goal, some evidence suggests that in reality patients may experience “treatment inertia,” that is, a delay in the switch to a medically more advantageous treatment ³² even if their current treatment might be regarded as sub-optimal. ³³ From this perspective, paving the way to a broader and earlier access of novel therapies could help overcome this “inertia” and possibly reduce patient burden ³⁴ by better aligning treatment choices with patient preferences.

This Delphi consensus project brought together MG specialists (from Scandinavia, the Benelux countries, and the Alpine region) whose active involvement in clinical trials and practice has contributed to shaping gMG management in Central and Northern Europe (CENE), with some specialists directly contributing to national guidelines, and all having some experience in implementing these guidelines in clinical practice. To our knowledge, few studies in the CENE region have explored the application of guidelines in practice, especially with a focus on identifying patient groups who are likely to best benefit from innovative therapies, and more importantly, the right time to start these treatments, considering the appropriate benefit-risk-long–term cost outcome. In doing so, the panel aims to carve a harmonized way toward more patient-centered gMG management.

Methods

Overview

A Delphi method was employed to systematically identify expert opinion across a geographically diverse panel of experts. This method was chosen because, in areas with limited clinical evidence, structured consensus is often relied on to guide decision-making. This project was a two-phase study employing a mixed-method approach. In the first phase, an international advisory board meeting (AdBoard) was conducted online in June 2024, with seven experienced healthcare professionals (HCPs) representing Austria, Finland, Sweden, Switzerland, and the Netherlands, and two patient advocacy group (PAG) representatives from Denmark and the Netherlands. All participating HCPs were medical doctors specializing in neurological or neuromuscular disorders. In the second phase, a two-round Delphi survey was conducted on a specialized online platform in Quarter 4 2024. Sixteen experienced HCPs participated in the Delphi consensus surveys, six of whom had previously participated in the AdBoard. These medical doctors represented Austria, Denmark, Finland, Norway, Sweden, and Switzerland.

Among the identifying criteria for participants were a focus on CENE countries and English-speaking participants to improve international coordination. All the participating HCPs had extensive experience in the management of gMG in their respective countries, with some HCPs indicating over 30 years of clinical practice. All HCPs were involved in treating patients in hospitals, specialized centers, or private practice settings. HCPs had clinical or trial experience with innovative, novel therapies, with some serving on national and international guideline committees. The PAG representatives who participated in the AdBoard were identified with thoughtful consideration given to their experience with the disease, patient advocacy, and comfort in partaking in a discussion alongside HCPs. All participating PAG representatives had decades of leadership experience within their respective advocacy groups. The following Figure 1 presents an overview of the research methodology, and Figure 2 highlights the countries represented by participants.

Figure 1.

Overview of the two-phase research methodology. The first phase was an international advisory board meeting of a panel of experts, including healthcare professionals and patient representatives. The second phase was a two-phase Delphi survey with an expanded panel of experts.

Figure 2.

Overview of the total number of participants in both study phases and their national representation. The panel represented seven Central and North European countries, focusing on the Alpine and Nordic regions. One participant each from Denmark and the Netherlands were patient representative who only participated in phase I and contributed to idea generation.

Delphi survey development

All participants were provided with information leaflets ahead of the AdBoard conduct. Both HCPs and PAG representatives received clear communication on key topics, terminologies, and definitions to ensure alignment. Using physician- and patient-specific prompts, a trained moderator led the first phase AdBoard discussion on key topics related to gMG management, such as patient needs, patient-physician communication, treatment approach, time-to-switch treatment, and patient profile considerations for novel therapy prescription. Using meeting records, this was thematically assessed to identify confirmed insights from prior research, new considerations, and gaps. The latter two bodies of findings were subsequently used to draw a Delphi survey. The draft questionnaire was piloted with one HCP, and based on the feedback, the questionnaire was updated for clarity and accuracy before launch.

Delphi survey execution

The Delphi survey was hosted on a specialized online platform and was used to collect quantitative and qualitative data. It utilized a 6-point Likert scale (strongly disagree, disagree, somewhat disagree, somewhat agree, agree, and strongly agree), with the option to provide free-text comments. All survey questions were mandatory, ensuring a 100% completion rate. Round 1 was launched in mid-October 2024 with a 4-week response period. The survey response was assessed for opinion consensus, wherein a positive medium consensus was obtained when ⩾70% of participants agreed or strongly agreed to a statement. If this agreement level was ⩾80%, a positive high consensus was obtained. Conversely, if ⩾70% of participants disagreed or strongly disagreed with a statement, it formed a medium negative consensus, and ⩾80% disagreement was a negative high consensus. Statements that had reached consensus (medium or high) in Round 1 were not included in the Round 2 survey. Additionally, in Round 2, participants were provided with a statistical report of their individual and group responses from Round 1, including the mean, mode, median, and frequency distribution along the 6-point Likert scale. This approach allowed participants to compare their individual responses to the group response. Round 2 was launched in early December 2024 and concluded with a 4-week response period.

In both rounds, participants were requested to record their responses considering an ideal scenario, which may or may not reflect their real-world experiences. Table 1 presents further information regarding participant roles and responsibilities.

Table 1.

Delphi consensus project participants.

Study phase	Participant (N)	Role
International Advisory Board	HCPs (7)	The participating HCPs were responsible for idea generation on key aspects of gMG management. Their participation in this systematic group discussion and input produced findings that were incorporated into the design of the Delphi survey.
International Advisory Board	PAG representatives/gMG patients (2)	The participating PAG representatives were responsible for idea generation on key aspects of gMG management, particularly from the patient perspective. Their participation in this systematic group discussion and real-world context produced findings that informed the design of the Delphi survey.
Delphi Survey Pilot	HCPs (1)	This HCP was responsible for reviewing, editing, and finalizing the Delphi Survey draft ahead of its launch.
Delphi Consensus Survey Rounds	HCPs (16)	The participating HCPs were responsible for responding to the Delphi surveys and providing written qualitative data to support their opinion. As leading regional experts specializing in gMG management, their input produced evidence that determined the research outcomes.
Independent Support	Clinical research organization and Sponsor (4)	Cytel, an independent clinical research organization in Germany, was responsible for supporting the Delphi survey development and conduct of voting rounds. Alexion, AstraZeneca Rare Disease supported as the study sponsor, additionally providing guidance to identify relevant HCPs.

Participants in the two phases of this study included health care providers and PAG representatives, as well as external consultants.

gMG, generalized myasthenia gravis; HCP, health care provider; PAG, patient advocacy group.

Results

Consensus statements

The Delphi survey consisted of 26 questions. Together with their sub-parts, the 26 questions contributed to 51 statements in total. The survey had a 100% completion rate in both rounds. At the end of Delphi Round 1, 47% (24 of 51) of statements had attained consensus and were not included in Round 2. In Round 2, 33% (9 of 27) of the remaining statements achieved consensus. In all, 65% (33 of 51) of statements achieved consensus. None of the statements achieved a negative consensus, as no statement received disagreement or strong disagreement from more than 70% of participants. The full result of the survey is attached to the Supplemental Material.

Patient profile identification for novel therapy use

Six Delphi survey questions, amounting to 19 statements, were aimed at identifying patient profiles most suited for treatment using novel therapies (Table 2). Of these, 79% (15 of 19) statements achieved consensus, 20% (3 of 15) with positive medium consensus, and 80% (12 of 15) with positive high consensus.

Table 2.

Delphi survey questions directed at identifying patient profiles most suited for treatment using novel therapies.

N.	Delphi survey question/statement	Consensus a (%)
1	For AChR-ab-positive gMG patients experiencing myasthenic exacerbation or crisis, the most appropriate treatment option is
	(a) PLEX	100%
	(b) FcRni	88%
	(c) IVIg	81%
	(d) C5i	81%
	(e) Steroid pulse therapy	75%
	(f) Rituximab	No consensus
2	For gMG patients considered non-responders to conventional first-line treatments (of crisis/exacerbation b ; e.g., IVIg, PLEX, and steroid pulse) of a myasthenic exacerbation or crisis, the most appropriate second-line treatment is
	(a) C5i	94%
	(b) FcRni	81%
	(c) Rituximab	81%
3	For severe AChR-ab-positive gMG, adding novel therapy options to the standard of care is considered, especially in these patient profiles
	(a) Patients who have intolerable side effects from standard immunosuppressants	100%
	(b) Patients who have persistent hard-to-control symptoms	88%
	(c) Patients with multiple comorbidities	75%
	(d) Patients with comorbid autoimmune conditions	No consensus
4	Patient-reported quality of life and personal experiences with the disease, along with objective clinical assessments, are given significant weight when considering the use of a novel therapy in gMG treatment	81%
5	The level of steroid dependence that strongly indicates the time to initiate steroid-sparing treatment is
	(a) Long-term steroid use between 5 and 10 mg/day (prednisone equivalent)	No consensus
	(b) Long-term steroid use of >10 mg/day (prednisone equivalent)	81%
6	For severe AChR-ab-positive gMG patients, adding novel therapy options to standard of care is considered especially appropriate in these events
	(a) Where consistent symptom control is of utmost importance	81%
	(b) Where rapid symptom control is of utmost importance	75%
	(c) Where long-term durable symptom control is of utmost importance	No consensus

The consensus level was calculated as the percentage of participants (total N = 16) who agreed or strongly agreed with a statement.

^aThe statements are ordered by % consensus to improve readability. The panelists may have responded to a different order of statements in the original survey questionnaire as indicated in the Supplemental Material.

^bThe original survey did not contain this phrase. However, HCPs assumed a crisis/exacerbation patient context. As such, the question is amended here. For the original survey draft, please refer to the Supplemental Material.

AChR, acetylcholine receptor; C5i, complement inhibitors; FcRni, Fc receptor inhibitor; gMG, generalized myasthenia gravis; HCP, healthcare professionals; IVIg, intravenous immunoglobulin; PLEX, plasma exchange.

Statement 1 focused on appropriate treatment for AChR-antibody-positive patients experiencing exacerbation or crisis. Consensus was achieved for all choices except rituximab. Panelists commented that rituximab did not act fast enough to be used in the acute phase and should be used for chronic treatment. Steroid pulse therapy received a medium consensus, with comments reporting occasional events of initial aggravation or slower effects. Interestingly, C5i and FcRni achieved as high or higher consensus levels than intravenous immunoglobulin (IVIg), despite several comments noting that current guidelines did not recommend these for the acute phase, while IVIg is recommended and widely used for acute phases. This high consensus was attributed to HCP experience with the rapid onset of action of C5i and FcRni, although they noted the current lack of clinical or long-term evidence.

Statement 2 focused on appropriate second-line treatment for patients experiencing exacerbation or crisis who were considered non-responders to conventional first-line therapies. Among C5i, FcRni, and rituximab, the highest consensus was achieved for C5i. In their comments, panelists indicated that insufficient response to IVIg and plasma exchange (PLEX) may indicate potentially low response to FcRni. Despite the consensus, comments underlined that preferences for C5i and FcRni were theoretically made considering an optimal scenario, but in the real-world, access to these therapies is constrained in most healthcare settings.

Statement 3 focused on AChR-antibody-positive patient profiles for whom the addition of novel therapies to the standard of care would be deemed appropriate. Apart from patients with autoimmune comorbidities, consensus was achieved on other patient profiles. Panelist comments highlighted that treatment choices were subject to the severity of individual cases. Importantly, the potential of novel therapy as a bridging therapy was discussed in comments. Additionally, some panelists discussed the difficulties of treating comorbid patients and the risks associated with using two biologics, while others touched on the potential for novel therapies in IgG autoantibody autoimmune comorbidity.

The panelists achieved a high consensus on statement 4 regarding the importance of patient-reported QoL and personal experiences when considering the use of novel therapy. However, comments stated that despite being the ideal, current clinical practices lack ways to incorporate patient-reported issues or MG-related QoL issues in treatment decision-making.

Statement 5 focused on identifying consensus on the thresholds of steroid dependence that indicate the need for steroid-sparing treatments. Long-term steroid use at 5–10 mg/day did not achieve consensus as a significant threshold, with some panelists noting that daily dosage up to 5–7.5 mg (or prednisone equivalent) may be well-tolerated, well-managed, or even desirable in some patient groups. With side effects varying between individual cases, panelists affirmed that ideally, the side effect profile and not the absolute dose affects treatment decision. Nonetheless, with high consensus, panelists agreed that over the long term, a daily dose of 10 mg steroid or higher was undesirable.

Lastly, statement 6 related to the utility of adding novel therapies to the standard-of-care for AChR-antibody-positive in three events—for rapid, consistent, and long-term symptom control. The first option obtained a high consensus. The second option obtained a medium consensus, with some panelists noting their reservations about the lack of sufficient evidence. The final option did not achieve consensus, with most comments noting the lack of sufficient data on long-term use.

Treatment-switch criteria for novel therapy prescription

Four Delphi survey questions, amounting to nine total statements, were directly aimed at identifying treatment-switch criteria or optimal timing to prescribe novel therapy for patient groups that were most suited for treatment using novel therapies (Table 3). Of these, two statements did not obtain consensus.

Table 3.

Delphi survey questions directed at identifying treatment-switch criteria for prescribing novel therapies.

N.	Delphi survey question/statement	Consensus a (%)
1	Failure to achieve minimal manifestation status within 12 months of conventional treatment indicates the need for novel gMG therapies.	No consensus
2	When a patient experiences lack of sufficient response with two or more treatments, it strongly indicates the need to switch to approved novel therapies such as C5i or FcRni in gMG management	76%
3	The inability to taper steroids below 10 mg daily (Prednisone equivalent) within the following period strongly indicates the need to initiate innovative steroid-sparing therapies in gMG
	(a) After 6 months of therapy	75%
	(b) After 12 months of therapy	81%
4	The following clinical factors strongly indicate the time to switch to novel therapy (C5i or FcRni)
	(a) Two or more hospitalizations in a year	81%
	(b) Two or more episodes of exacerbation or crisis in a year	81%
	(c) Heavy side effects due to conventional immunosuppressives (e.g., weight gain)	81%
	(d) Deterioration from a state of minimal manifestation	75%
	(e) Frequent fluctuation in symptoms	No consensus

The consensus level was calculated as the percentage of participants (total N = 16) who agreed or strongly agreed with a statement.

^aThe statements are ordered by % consensus to improve readability. The panelists may have responded to a different order of statements in the original survey questionnaire as indicated in the Supplemental Material.

C5i, C5 inhibitors; FcRni, FcRn inhibitors; gMG, generalized myasthenia gravis.

Statement 1 stated that a failure to achieve minimal manifestation within 12 months of conventional treatment indicated the need for novel gMG therapies. This statement did not achieve consensus. Panelists exhibited contrasting opinions; some commented 12 months as the maximum acceptable waiting time, while others did not deem 12 months to be sufficiently long after treatment initiation. Of particular concern was the longer onset of action of commonly used conventional therapies. Overall, two topics emerged—the need to individualize decision-making based on patient-specific factors, such as burden or QoL, and a preference to escalate other treatments (current, other treatments acting earlier in the immune cascade, or rituximab) before considering C5i and FcRni.

Statement 2 stated that a lack of sufficient response to two or more treatments strongly indicated the time to switch to novel therapies. This was supported with a medium consensus. The question of cost-effectiveness featured heavily in comments, reflecting that even in an ideal situation, specialists consider cost constraints in their treatment decisions, preferring an escalation of current treatment or alternative conventional therapies. Even when a switch was desirable, panelists reported that approval hindrances and hospital budget concerns may put novel therapies out of reach. Lastly, comments reflected that in practice, treatment-switch decisions were not only a question of how many treatments failed, but rather which treatments failed.

Statement 3 focused on obtaining consensus on a time-to-switch category based on steroid dependence. Consensus was achieved that failure to taper steroids below 10 mg daily (or prednisone equivalent) within 6- or 12-months indicated the need for steroid-sparing therapy. This indicated panelists’ disinclination to rely on high-dose steroid treatment over extended periods of time.

Lastly, statement 4 stated five clinical factors that may indicate the time to switch to novel therapies. No consensus was achieved on frequent symptom fluctuation. Panelists commented that, given the inherent fluctuating nature of MG, this did not qualify for the treatment-switch category. Despite a medium consensus for “deterioration from a state of minimal manifestation,” open text comments threw caution that mild and short-term deterioration would not warrant a switch, unless conventional bridging therapies fail. Episodes of hospitalizations, exacerbations, crises, and heavy side effects from immunosuppressants were supported with high consensus as relevant switch categories. Panelists found these profiles to align with guideline-recommended use of novel therapies. Regardless, comments indicated that panelists had varied opinions as some preferred C5i due to their experience of C5i reducing exacerbation and hospitalization, while others noted a lack of evidence, and yet others had no preference.

Discussion

The patient burden of MG can sometimes be profound. From physical, professional, social, and psychological impacts, the burden of uncontrolled or delayed symptom control extends to personal life—affecting relationships with immediate and caregiving family members. ³² Reasonably, effective symptom control with minimal side effects is a key priority for patients. ³¹ This consensus project engaged HCPs to gather expert opinion based on an ideal scenario, while recognizing the role of regulatory and payer barriers in ensuring cost-effective care. Particularly, this study focused on identifying patient groups who may benefit meaningfully from novel therapies,^16–21 and in whom a treatment switch could be considered. By contrasting ideal scenario outcomes with real-world experience, this study highlighted gaps in implementing national and regional guidelines. Consequently, consensus outcomes offer insights into effectively applying guidelines to treatment decisions in clinical practice and potentially improve patient access to innovative therapies despite existing constraints. Notably, the results of this consensus are primarily applicable to AChR-antibody-positive gMG and have limited generalizability to other subgroups (MuSK-Ab, LRP4-Ab, seronegative). This reflects the fact that AChR-antibody-positive gMG constitutes the majority of gMG cases, and that Delphi statements in this project specifically referred to this group when subpopulation-specific considerations were addressed. In addition, this consensus project focused on pharmacological approaches to the management of MG, and other interventions, such as thymectomy, which are critical for MG symptom control, were intentionally set aside for future research.

Across different guidelines, novel therapies have been recommended for “difficult to treat,” ²³ “refractory,” ²⁴ and “severe MG not responding to standard immunosuppressive treatment.” ²⁵ This project identified that these terminologies refer to similar patient profiles, with differences arising due to a lack of international harmonization on key definitions and heterogeneity of disease. Results confirmed that HCPs regard existing guidelines highly in their clinical practice. This is reflected in the high consensus obtained on the relevance of novel therapy prescription for patients with intolerable side effects to standard immunosuppressants (88%), persistent hard-to-control symptoms (100%), or experiencing exacerbation and crisis after failure of IVIg and PLEX (81%–94% consensus for FcRni, rituximab, and C5i)—clinical profiles deemed to align with the current guideline recommendations.

Notably, high consensus was also observed for the appropriateness of novel therapies (except rituximab) among AChR-antibody-positive patients experiencing exacerbation or crisis. This contrasts with current guidelines that prioritize IVIg and PLEX and do not recommend novel therapy as first line treatment option for acute patients due to a lack of clinical or long-term RWE. Despite noting this limitation in their comments, HCPs’ experience with the rapid onset of action of C5i and FcRni contributed to high consensus for this clinical profile. Moreover, with the survey statements focusing on identifiable clinical profiles such as “frequent hospitalization” or “deterioration from minimal manifestation,” consensus helped address ambiguous terminologies such as “highly active” or “refractory to therapy.” Further, consensus statements identified previously undescribed patient profiles who could benefit from innovative therapies, such as patients with multiple comorbidities (excluding autoimmune comorbidities; 75%), patients who require rapid symptom control (88%), or where consistent symptom control is of utmost importance (75%), prompting a call to reassess MG management in the changing treatment landscape.

Further, the findings from this project underlined a critical discrepancy between what HCPs considered an ideal treatment approach versus their real-world experience. With 81% consensus, HCPs agreed that ideally, patient-reported QoL and experiences would play a significant role in their novel therapy prescription practices. However, notably there are few current standardized practices to integrate these into formal treatment decisions. There was also uncertainty among the HCPs about what exactly constitutes “severe side effects” that potentially justify the switch to novel therapies. For example—several HCP comments indicated that in clinical practice, side effects such as weight gain or mental health issues were not always sufficiently weighted when making treatment decisions. Arguably, this view favors systematically considering patient experiences through patient-reported outcomes and QoL measures, a point on which consensus was achieved. This point is also emphasized by RWE that patients are dissatisfied with how well physicians seem to understand, in the patients’ view, the impact of MG on their QoL and overall functioning.^31,32

The consensus outcomes highlighted that HCPs are aware of the long-term health risks associated with sustained steroid use and generally prioritize tapering—ideally aiming for a complete cessation when feasible. Indeed, a key outcome was the agreement on a threshold daily dose (10 mg) and duration (6 months) of steroid use as a basis for initiating steroid-sparing treatment. This contrasts with real-world observations where tapering is often delayed. For example, a Europe-wide physician and patient survey reported continued chronic steroid use as first-line treatment despite persistent moderate to severe symptoms. ³³ Steroid tapering or discontinuation is emphasized in guidelines, given numerous potentially major side effects, amongst them diabetes mellitus, osteoporosis, or mental health issues. This is an important consideration for HCPs, as treatment of multi-co-morbid individuals may be complex and risky, with severe mental health comorbidity affecting patient treatment adherence.

Another finding of this study was the identification of novel therapies for use as bridging therapies. This could potentially offer a targeted approach in the current set-up when long-term use is limited due to cost or clinical evidence constraints. Bridging therapies could provide transitional care needs, for example, when traditional treatments do not act fast enough, and respond to patient-reported experiences of treatment delays. ³²

Key findings also extended to non-consensus statements, such as the non-consensus on a 12-month wait time for minimal manifestation from conventional therapy before switching to novel therapies. While 62% of HCPs agreed with the statement, 38% HCPs disagreed or remained neutral. Clearly, if the aim were to harmonize the prerequisites for escalating or switching the mode of action of treatments, it would be important to identify an upper limit until which a minimal manifestation status should have been achieved. In fact, “treatment inertia,” that is, the delay of an otherwise medically necessary change of treatment, and the necessity for a trial-and-error approach are identified as important points of grievance for MG patients.^31,32

Similarly, other non-consensus statements worth exploring in further research include the use of novel therapies in patients with autoimmune comorbidities—with almost 69% of HCPs agreeing and 19% HCPs disagreeing with the statement, this indicates an unexplored potential of novel therapies in a difficult-to-treat patient group. Panel consensus also failed to support novel therapy use for long-term, durable symptom control, which requires further research. Moreover, while HCPs identified the upper limit for tolerable long-term use of steroids, there was no consensus on a lower limit. These outcomes confirm what is known of MG management—its patient-tailored and evolving approach and further enrich it with real-world context to support, challenge, and improve it.

In the European context, the objectives of this Delphi project are particularly relevant. Given the higher MG prevalence in an older population, patients may be burdened with comorbidities or risk of side effects contributing to treatment complexity. In addition, HCPs may face challenges in identifying root causes of dissatisfaction, including reduced QoL and symptoms such as fatigue. In this context, knowledge of clearly identifiable patient profile considerations and treatment-switch-categories may support timely access to innovative therapies, for their quicker effect and favorable safety profiles could improve patient-centric care. ³⁴

Overall, with a 65% consensus achieved in this Delphi survey, this project highlights both the growing areas of agreement and the persisting differences in expert opinion. Achieving consensus on nearly two-thirds of the statements underscores the inherent complexity of individualized MG management and the variability in clinical practice across regions. Continued research and expert dialogue are key to continuously refining and standardizing the evolving therapeutic landscape.

Conclusion

In this Delphi survey, 65% (33 of 51) statements achieved consensus, highlighting areas of clear agreement as well as areas of continued heterogeneity of opinion among MG experts. This consensus project produced strong evidence that the participating HCPs engage with and apply national and regional guidelines in clinical practice, while noting that guidelines are not meant to replace treatment decisions tailored to individual patients. By relying on expert opinion, this study identified ways to apply guidelines to support patient-centric implementation. It reported RWE on the clinical application of guidelines, identifying areas of alignment, misalignment, and where further research is necessary. Through international collaboration, this panel of experts identified standardized patient profile criteria likely to benefit from innovative therapies, as well as the relevant treatment-switch criteria. Following these outcomes, this study identifies that building a uniform set of criteria and standards can improve guideline application, patient access to innovative drugs, and generate further RWE.