Findings from the “Leeds SLE Inception Cohort”

If systemic lupus erythematosus (SLE) cannot be adequately controlled with hydroxychloroquine and cortisone preparations, the use of immunomodulatory or immunosuppressive agents and/or biologics should be considered according to current EULAR recommendations. Data from a British longitudinal study with a follow-up of over 30 years shows that certain predictors predict which patients will benefit most from early intensified therapy with biologics.

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease with various clinical manifestations. Those affected produce antibodies against the body’s own tissue structures, so that autoantibodies reach various parts of the body via the bloodstream, which can lead to inflammation of connective tissue, joints or organs. The diagnosis is based on the EULAR/ACR classification criteria [1]. Typically, antinuclear antibodies (ANA) and occasionally autoantibodies against double-stranded DNA (dsDNA) are found in SLE. The primary goal in the treatment of patients with SLE is to control disease activity and thus improve the quality of life of those affected. This is to be achieved by reducing inflammatory processes and the occurrence or severity of relapses. Which treatment is used depends, among other things, on which organs are affected and how frequent and severe the relapses are.

What do the EULAR recommendations, updated in 2023, recommend?

The current EULAR guidelines on the management of SLE emphasize the importance of the following four pillars [1]:

• Early diagnosis: Despite improved awareness and more sensitive classification criteria, the median diagnosis latency according to recent studies is still 2 years from the first manifestation of symptoms [2–4].
• Monitoring: Especially during the first years of the disease, but also afterwards, monitoring for new organ involvement is an important factor. Recognizing signs of emerging renal involvement is particularly important, as lupus nephritis represents an important milestone in the natural history of the disease and a delay in diagnosis has profound prognostic implications.
• Clearly defined treatment goal: Ideally, remission according to the latest DORIS (“Definition Of Remission In SLE”) criteria or, alternatively, low disease activity according to LLDAS (Lupus Low Disease Activity state) should be aimed for [5]. These are validated treatment goals, the achievement of which has been shown to reduce the risk of damage and other negative consequences of SLE [6].
• Therapy adherence/compliance: The fourth pillar emphasizes the importance of patient adherence to therapy.

If SLE cannot be permanently controlled by hydroxychloroquine (as monotherapy or in combination with cortisone preparations) or high steroid doses are required, the addition of immunomodulatory or immunosuppressive agents (e.g. methotrexate, azathioprine or mycophenolate mefotil) and/or the biologics belimumab or anifrolumab should be considered according to the EULAR recommendations updated in 2023. In SLE patients with organ-threatening or life-threatening manifestations, the guideline advises considering intravenous cyclophosphamide or, in refractory cases, rituximab.

Longitudinal study on intensified therapy strategy

A treatment strategy with early intensive therapy may be able to counteract severe SLE progression and accumulative damage, provided that high-risk patients are identified in the appropriate time window. According to Dr. Porntip Intapiboon from the University of Leeds (UK), there are basically two groups of SLE patients who can benefit from an intensified treatment strategy with biologics or cyclophosphamide [7]:

• Patients who have severe SLE at the time of diagnosis,
• Patients with a mild form of SLE who show an inadequate response to conventional treatment (see above).

Whether there are specific cut-off values for disease activity and complement levels that can be used to guide therapy has not yet been clarified. To find out more about this, Intapiboon et al. conducted a retrospective analysis in which all patients with an SLE diagnosis from two “Leeds SLE Inception Cohort” databases with a follow-up of over 30 years were included [7].

A total of 229 SLE patients were included, 91.3% of whom were female; the mean age at SLE diagnosis was 38.8 (SD14.7) years (Fig. 1) [7]. Intensive therapy was initiated in 48.1% (n=110) of patients; 17.0% (n=39) within one year and 24.0% (n=55) within two years of diagnosis. The median time from SLE diagnosis to the start of intensive therapy was 2 years (IQR 0.5-8).

Univariate analyses showed that during the first two years after SLE diagnosis, positive anti-Ro antibodies (SS-A), low complement levels, a score ≥20 according to EULAR-ACR criteria and a higher Systemic Lupus Erythematosus Disease Activity Index-2K (SLEDAI) score were associated with an increased likelihood of intensified therapy. In the ROC analysis, a SLEDAI score of ≥9 was identified as a relevant cut-off value. And the multivariate analysis showed that low complement levels and a SLEDAI score of ≥9 were associated with an increased likelihood of intensified therapy (Table 1). According to Dr. Intapiboon, the question of the treatment sequence for SLE has not yet been clearly clarified. The results of the present study indicate that patients with the identified predictors have a higher risk of developing a more severe form of SLE and a poor response to conventional therapies. These subgroups of SLE patients may benefit from first-line therapy with biologics, the study concludes.

Congress: EULAR Annual Meeting

Literature:

1. Fanouriakis A, et al: EULAR recommendations for the management of systemic lupus erythematosus: 2023 update. Ann Rheum Dis 2024; 83(1): 15-29.
2. Aringer M, et al: European league against rheumatism/American college of rheumatology classification criteria for systemic lupus erythematosus. Ann Rheum Dis 2019; 78: 1151-1159.
3. Kapsala NN, et al: From first symptoms to diagnosis of systemic lupus erythematosus: mapping the journey of patients in an observational study. Clin Exp Rheumatol 2023; 41: 74-81.
4. Kernder A, et al: Delayed diagnosis adversely affects outcome in systemic lupus erythematosus: cross sectional analysis of the lula cohort. Lupus 2021; 30: 431-438.
5. van Vollenhoven RF, et al: DORIS definition of remission in SLE: final recommendations from an international task force. Lupus Sci Med 2021; 8: e000538.
6. Franklyn K, et al: Definition and initial validation of a lupus low disease activity state (LLDAS). Ann Rheum Dis 2016;75: 1615-1621.
7. Intapiboon P, et al: identifying a population of patients for intensive first-line therapy in SLE: a clinical and biomarker model to predict the need for intensive therapy, OP0187, EULAR Annual Meeting, Vienna, 12-15 june, 2024.

HAUSARZT PRAXIS 2024; 19(8): 22-24 (published on 22.8.24, ahead of print)