Evaluation of the Mainz Lupus Score: a clinical support tool for managing Systemic Lupus Erythematosus

Introduction

Systemic lupus erythematosus (SLE) is a clinically heterogeneous autoimmune disease primarily affecting young women. Current data for Germany estimate a prevalence up to 79.8/100,000 in women and 13.8/100,000 in men, respectively, within a range of 0.037%–0.14%, and an incidence of 8.86 per 100,000 for 2019 (1–3).

Characterized by multi-organ involvement, circulating autoantibodies, and a highly variable relapsing-remitting clinical course, SLE presents unique challenges in diagnosis and treatment (4, 5). The control of disease activity, the reduction of potential damage accrual, and the patient's quality of life should be the goals to focus on (6). Although clinical efforts have improved the management and treatment of SLE, there are still unmet needs for patients and physicians (5). Recent advancements in SLE treatment emphasize the early use of lupus-specific biologics and achieving remission via a treat-to-target approach (6–12).

However, the heterogeneity of clinical manifestations and disease courses poses challenges, particularly for less-experienced clinicians in diagnosing and, especially, in the individualized management of SLE.

Although several validated instruments are available to assess disease activity and organ damage in SLE, studies have demonstrated a persistent gap between guideline recommendations and their implementation in routine clinical practice. The increasing complexity of SLE management, including treat-to-target strategies, biologic therapies, and shared decision-making may be particularly challenging for physicians who are less familiar with lupus care. Therefore, there is a need for practical tools that facilitate the translation of recommendations into everyday clinical decision-making.

To address this, the Mainz Lupus Score (MLS) was developed as an adjustable tool for a multidimensional approach to lupus management. The MLS was conceived as a pragmatic clinical support tool rather than a novel disease activity index. Its primary objective is to assist physicians with limited experience in lupus management by providing a structured assessment of disease-related changes and by supporting decisions regarding whether therapeutic adaptation should be considered.

Unlike established scores, the MLS incorporates the subjective assessment of patients in addition to objective measures. Especially in times of individualized decision-making, including patient preferences and shared decision-making as key overarching principle in SLE management, the subjective Quality of Life (QoL) is essential to consider (6, 9).

A deliberate component of the MLS is the inclusion of patient-reported quality of life. While established activity indices primarily focus on objective manifestations of disease, symptoms such as fatigue and impaired well-being substantially contribute to disease burden and are often insufficiently reflected in conventional disease activity scores. The MLS therefore integrates patient-reported information to complement objective clinical assessment and facilitate patient-centered therapeutic decisions. For example, fatigue has been shown to be independently associated with disease activity when assessed using the patient's global assessment, but not when measured by the SLEDAI (13).

The aim of the study is to evaluate the MLS by comparing it with established indices such as the SLE Disease Activity Index (SLEDAI), the clinical SLE Disease Activity Index (cSLEDAI), the European Consensus Lupus Activity Measurement Index (ECLAM), and the Systemic Lupus Erythematosus International Collaborating Clinics index (SLICC) as established scores in SLE, while also assessing correlations with subjective outcomes like the Fatigue Severity Scale (FSMC), the Beck Depression Inventory (BDI), and the Work Ability Index (WAI) (14–22).

Methods

Development of the Mainz Lupus Score (MLS)

The MLS was developed at the Mainz Lupus Center, a tertiary referral center currently caring for approximately 700 patients with SLE and related autoimmune diseases. The development process was conducted over approximately one year through multiple iterative consensus rounds involving experienced lupus specialists and junior physicians. The primary goal was to create a practical tool that translates current SLE management recommendations into a format that can be readily applied during routine outpatient visits.

Candidate domains were selected based on their perceived importance for therapeutic decision-making and their relevance within contemporary SLE treatment recommendations. Particular emphasis was placed on creating a score that captures both objective disease manifestations and the patient's subjective perspective. Consequently, the MLS combines information on new lupus-related symptoms, quality of life, laboratory abnormalities, and organ damage.

The categorization of individual items and weighting of score components were derived pragmatically and refined through repeated use within the center. The objective was to maximize agreement between therapeutic decisions made by experienced lupus experts, guided by current recommendations, and decisions reached by less-experienced physicians using the MLS. The resulting score categories were intentionally designed to support clear therapeutic interpretation and facilitate routine clinical decision-making rather than to establish a new psychometric disease activity index.

The Mainz Lupus Score (MLS) questionnaire

The MLS consists of four items that assess the need for adjustments in current therapy (Figure 1). These items include: i) the occurrence of new lupus-specific symptoms, ii) the subjective measurement of quality of life (QoL), iii) changes in serological abnormalities, and iv) the occurrence of organ damage.

• (1) New symptoms

The first item assesses whether new lupus-specific symptoms have occurred. This question is answered with a simple “yes” or “no,” receiving scores of “5” or “0,” respectively. The evaluation period considers the preceding 2 to 4 weeks.

All symptoms included in SLEDAI and ECLAM were accepted as new lupus-specific symptoms. This item does not differentiate by intensity of symptoms, affected organ systems, or manifestations. Every new symptom indicates an increase of disease activity and should therefore be taken into account. The second section focuses on the patient's subjective assessment, with the most important sub-item being the evaluation of disease activity as a marker of QoL using a visual analog scale ranging from 0 (“good”) to 10 (“poor”). For MLS scoring, the ranges are weighted as follows: 0–3: 0 points, 4–6: 1 point, 7–10: 3 points. Laboratory results are a critical clinical component of the MLS. Normal laboratory findings are scored as “0.” Stable abnormalities are scored as “1,” while newly occurring or aggravated abnormalities are scored as “3.” The laboratory parameters considered include nonspecific changes such as anaemia, lymphopenia, thrombocytopenia, and elevated erythrocyte sedimentation rate (ESR), as well as more specific findings such as low complement levels (C3, C4, CH50) and elevated ANA (dsDNA, Sm, U1-RNP antibodies). Urinalysis findings, including proteinuria and active sediment, are also significant as signs of potential kidney involvement. Comparing current results with previous laboratory data is crucial for determining the stability or progression of abnormalities. The parameters are in accordance with the 2019 EULAR/ACR criteria for the Classification of SLE (23). The final item evaluates lupus-related end-organ damage, including kidney involvement, central nervous system complications, or cardiac deterioration due to cardiovascular involvement. Scores are assigned as follows:

• (2) Subjective assessment (Quality of Life)

• (3) Laboratory findings

• (4) Organ damage

0 points for no organ involvement,

1 point for stable organ damage, same score in SLICC compared to the last assessment

5 points for exacerbated damage, higher score in SLICC compared to the last assessment.

This evaluation requires comparison with previous examinations.

Therapy-related adverse events require immediate adjustment of therapy.

Current medication, specifically the prednisolone dose is an additional part of the MLS Data to identify the activity state and to register which therapeutic adjustments were made.

To differentiate disease activity states the definition of the Lupus Clinical Trials for LLDAS and the DORIS criteria were used (24). It should be noted that the data were collected before the latest recommendations of EULAR, in which the prednisolone dose in LLDAS was limited by 5 mg/d. Furthermore, we decided not to rate the PGA even though in the original definition it was included. This decision was based on the fact that the consensus defined it as a parameter that requires substantial experience and may therefore be less suitable for less-experienced physicians.

Remission (RE): (SLEDAI = 0, prednisolone ≤5 mg/d, no immunosuppressants)

DORIS Remission on treatment (ROT): (SLEDAI = 0, Prednisolone ≤5 mg/d, stable antimalarials, immunosuppressants, and biologics),

Lupus low disease activity state (LLDAS: SLEDAI <4, Prednisolone ≤7.5 mg/d, no activity in major organ systems, immunosuppressants) and active disease (ACTIV) (7, 12, 25). The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), the European Consensus Lupus Activity Measurement Index (ECLAM), and the Systemic Lupus Erythematosus International Collaborating Clinics index (SLICC) are considered as objective lupus-specific scores for disease activity; the SLICC may be used as a reference for assessing cumulative organ damage (15, 19, 20).

Additional subjective scales, including the Fatigue Severity Scale for motor and cognitive aspects (FSMC), the Beck Depression Inventory (BDI), and the Work Ability Index (WAI) are recorded (16–18, 21).

While these do not contribute directly to the MLS score, they provide valuable insights into the patient's subjective condition and can help guide therapeutic decisions when necessary.

Scoring and interpretation

The MLS results in three score ranges, each associated with specific therapeutic recommendations (Figure 2):

0–2 points: No change in therapy.

3–4 points: This is a borderline range. The MLS recommends reviewing and potentially adjusting the therapy, guided by additional assessments such as the WAI and FSMC to determine trends.

5–16 points: Therapy escalation is clearly recommended. Therapy escalation is hereby defined as adjustments in medication but also including other supportive therapies depending on the manifestation.

Data were collected from 458 SLE patients treated at the University Medical Center Mainz since the introduction of the MLS in 2016. Patients with at least three consecutive visits were included in the analysis, enabling the longitudinal tracking of remission and disease activity. 93 patients with 422 visits were included. Descriptive data were presented as mean, standard deviation (SD), and percentage (%).

Spearman correlations were performed between the MLS and established disease activity indices (SLEDAI, cSLEDAI, ECLAM, SLICC). Additionally, scores assessing mental and physical status through PROs (FSMC, BDI, WAI) were analyzed to evaluate the applicability and expressiveness of the MLS. Patients were categorized based on disease activity into remission, DORIS remission, LLDAS, and active disease. Each patient was categorized only in the lowest activity group possible and not taken into account several times even though DORIS and LLDAS might be nested targets, but it was necessary for the monitoring of the progression of activity state over the observation time.

Associations between two continuous or ordinal variables were assessed using Spearman's rank correlation coefficient (rho). For comparisons between continuous variables and categorical disease activity groups, remission states, or patient-reported outcome categories, Kruskal–Wallis tests were performed. Therefore, Table 4 reports either Spearman correlation coefficients (rho) or Kruskal–Wallis test statistics, depending on the type of analysis performed. Post-hoc comparisons were conducted using Dunn's test with Holm correction for multiple testing where appropriate.

To evaluate the applicability of the MLS in daily clinical routine, the MLS score was compared to medical doctors' (MD) treatment decisions across all visits using a paired Wilcoxon signed-rank test, focusing on the outcome of remission. A potential change in remission status was measured in increments, with positive numbers representing improvement and negative numbers representing deterioration. For example, a change from LLDAS to DORIS remission corresponds to the value 1 (= improvement by 1 level), and a change from DORIS to active corresponds to the value −2 (= deterioration by 2 levels).

All analyses were performed using SPSS 28. The significance level was set to p < 0.05. Some significance levels are presented as p < 0.0001.

Results

The total lupus cohort includes 458 patients with SLE treated at the University Medical Center Mainz. The average age is 42.3 ± 13.6 years, with the majority of patients being female (88%). The average disease duration is 7.5 ± 4.9 years, and the average SLEDAI score is 4.4 ± 6.2, indicating moderate disease activity (Table 1).

Table 1. Characterization of the total lupus cohort.

Characterization of the MLS-sub-cohort with >3 visits

The sub-cohort comprises 93 patients with a total of 422 visits (4.5 ± 1.7 visits per patient), all of whom attended at least three visits since 2016 and for whom the Mainz Lupus Score (MLS) was determined. The average age is 46.9 ± 12.9 years, with the majority of patients in the cohort being female (92.5%). The average disease duration is 13.8 ± 8.5 years, and the average SLEDAI score is 3.5 ± 3.4, indicating moderate disease activity, and the average cSLEDAI score is 1 ± 2.9.

The major organ involvement included kidney (65%), skin (50%), and joint (35%) with a mean disease activity (SLEDAI) of 3.5 ± 3.4, comparable to the total cohort (Table 2). About 70% of the patients report a good quality of life, whereas only 4.4% report a poor quality of life. More than 50% of the patients are at least in remission while on treatment. Detailed data per visit are provided in Table 3.

Table 2. Overview of the 93 patients at visit 1 (baseline).

Table 3. Overview of all visits of all 93 patients having at least 3 consecutive consultations.

MD, Medical Doctor; MLS, Mainz Lupus Score.

Data analysis revealed significant correlations between the MLS and other disease activity scores: SLEDAI (r = 0.403), SLICC (r = 0.427), and ECLAM (r = 0.537), all with p < 0.0001. Table 4 outlines correlations between the MLS and various disease activity scores, also showing significant associations between MLS scores and PROs (p < 0.01).

Table 4. Association between MLS and established disease activity indices, patient-reported outcomes, and treatment-related parameters (N = 422).

*Significant p < 0.05.

Values are presented either as Spearman's rank correlation coefficient (ρ) for associations between continuous variables or as Kruskal–Wallis test statistics (H) for comparisons involving categorical variables. Corresponding p-values are shown for each analysis. Significant results (p < 0.05) are marked with an asterisk.

An additional focus was placed on the potential use of the MLS as a “treat-to-target” tool.

As expected, both the MLS and the cSLEDAI showed a significant correlation with remission (<0.0001), while a wider interquartile range in the LLDAS and Active Lupus stages was illustrated in Figures 3A,B.

Moreover, when testing the change in remission from visit to visit, we did not detect a significant difference between MLS-based and medical doctor (MD)-based therapy decision (N = 327, p = 0.9398) (Table 5).

Table 5. Comparison of MLS vs. medical doctors’ (MD) decision in previous visit.

Discussion

The Mainz Lupus Score (MLS) assesses four key items: the presence of new symptoms, the evaluation of quality of life (QoL), current laboratory findings, and the extent of organ damage. The essential aim is to determine, through repeated assessments, whether there are abnormalities and whether these are stable or indicate exacerbation. The development of the MLS reflects the heterogeneous clinical picture of SLE and its therapeutic management (4, 5). The complex, multidimensional information is captured in a score that, in turn, leads to three major pathways, providing a guideline for treatment decisions. The standardized presentation is intended to provide the attending physician with clear guidance. Ideally, as with the SLEDAI, this evaluation should be conducted quarterly. It should be noted that the purpose of the MLS is not to classify the disease itself, even though the parameters it covers align with the 2019 EULAR/ACR criteria for the classification of SLE; new organ damage is simply recorded as “yes” or “no” and is not further differentiated by stages, as is the case in lupus nephritis management (23, 26). It may be debated whether every symptom, irrespective of its severity, should justify treatment escalation or whether further refinement of the scoring system is warranted.

The scoring process typically takes only a few minutes for physicians, making it manageable for routine clinical use. It must be considered that the burden of lupus severity is multifactorial and, therefore potentially overlaps with fatigue or depression (27). The subjective scores, however, should ideally be completed by the patient prior to the visit, as they require slightly more time.

The MLS addresses a significant gap in SLE management by offering a clinically easy-to-use tool that combines objective measures and subjective patient experiences. Impaired subjective quality of life does not necessarily require an adjustment of pharmacological treatment; however, it might prompt consideration of adjunctive therapeutic strategies, including psychotherapy, nutritional counseling, physiotherapy, exercise therapy and other multidisciplinary supportive interventions aimed at improving patient-centered outcomes.

Importantly, the MLS was not developed to replace established instruments such as SLEDAI, ECLAM, or SLICC, nor was it intended to serve as a standalone disease activity index. Instead, it functions as a structured clinical support tool designed to facilitate implementation of contemporary treatment recommendations in routine care, particularly for physicians with limited experience in SLE management.

All relevant key points from current recommendations are covered (28).

The additionally collected subjective scores, together with the patient's QoL, enhance the utility of the MLS, particularly for clinicians less familiar with SLE, and support patient-centered therapy management and clinical decision-making.

The categorization of score components inevitably results in some loss of information compared with continuous variables. However, this simplification was intentionally chosen to provide clear and actionable therapeutic guidance during routine clinical encounters. The weighting and score thresholds were established pragmatically through iterative consensus within our center and optimized to achieve concordance between decisions made by experienced lupus specialists and those supported by the MLS.

Furthermore, the inclusion of patient-reported quality of life reflects the growing recognition that symptoms such as fatigue and impaired well-being contribute substantially to disease burden and therapeutic decision-making despite being insufficiently represented in many established disease activity instruments.

We acknowledge that the current study does not constitute a formal derivation and psychometric validation of a novel disease activity score. Rather, it evaluates the clinical applicability of a pragmatic decision-support instrument in a large real-world lupus cohort. Future multicenter studies will be necessary to further evaluate its performance, refine weighting strategies, and assess its generalizability across different healthcare settings.

The at least moderate or greater correlation with the established and widely used SLE scores, such as SLEDAI: r = 0.403, SLICC: r = 0.427, and ECLAM: r = 0.537, demonstrates the potential of the MLS. Not surprisingly, associations with PROs were weak or non-significant for fatigue and modest for depression and work ability (FSMC, BDI and WAI).

The results underscore its reliability, and the concordance between decisions guided by the MLS and those made by experienced physicians in the treatment of lupus highlights its potential as a promising tool for managing SLE in daily clinical practice.

However, while straightforward, the MLS may oversimplify the intricate interplay of SLE symptoms, potentially leading to under- or overtreatment. Though incorporating patient-reported outcomes is innovative, the moderate correlations indicate room for improvement in capturing patient experiences. Additionally, during our study, no distinction was made between previously diagnosed and newly diagnosed patients to use the MLS in a broader setup. Another limitation of the study might be that the data primarily reflect a single-center cohort. However, a comparison with the Swiss SLE Cohort Study (SSCS) or a Canadian 1,000 Faces of Lupus study examining up to 1,528 SLE patients reveals comparable demographic characteristics, indicating that the demographic and clinical features of our SLE cohort align closely with those reported in other international studies, underscoring the representativeness of our sample (29, 30). Yet, broader studies are necessary to confirm our findings. The Mainz Lupus Score represents a promising advancement in SLE management by combining simplicity, objectivity, and patient-centered measures. Its validation against established indices and alignment with treat-to-target goals highlight its potential as a reliable tool, particularly for less-experienced clinicians. However, further refinement and broader validation are essential to maximize its clinical impact.

Ultimately, therapeutic decisions should consider the entire clinical picture and involve shared decision-making with the patient. The MLS thus provides a practical adjustable framework for monitoring and managing SLE while emphasizing individualized care.

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Footnotes

Edited by: Ola Grimsholm, Medical University of Vienna, Austria

Reviewed by: Rahul Kakalij, University of Nebraska Medical Center, United States

Carmen Raya Santos, Complejo Hospitalario de Jaén, Spain