An Important Shift in Lupus Care

Ronald F. van Vollenhoven, MD, PhD


July 21, 2014

In This Article

Treat-to-Target in SLE (T2T/SLE)

The Treat-to-target Target in SLE (T2T/SLE) task force was convened on 3 occasions, and a considerable amount of work was done in the interim periods. During the first meeting, the key ingredients of treating to target were reviewed and redefined in the context of SLE, and 12 specific topics of importance were identified. These topics were studied through a systematic literature review, and the results were synthesized.

During a subsequent meeting, this analysis was extensively discussed and debated, followed by formal votes on most of these topics. Further work on each of the topics was accomplished through email discussions.

The final recommendations of the T2T/SLE working group were published recently in a peer-reviewed article.[12] In addition to a more detailed description of the process and an extensive reference list, the article includes the "meat" of the initiative: a set of 4 overarching principles and 11 bullet-point recommendations pertaining to treating to target in SLE.

The overarching principles were not based on scientific data, but rather reflected the humanistic values underpinning the care of patients with SLE:

The management of SLE should be based on shared decisions between the patient and her or his physician(s).

Treatment of SLE should aim at ensuring long-term survival, preventing organ damage, and optimizing health-related quality-of-life, by controlling disease activity and minimizing comorbidities and drug toxicity;

The management of SLE requires an understanding of its many aspects and manifestations; and

Patients with SLE need regular long-term monitoring and review, and/or adjustment of therapy.

The recommendations, in contrast, are solidly based on data from the literature obtained through systematic investigations of a list of key topics. The breadth and strength of the scientific data underlying each recommendation varied: For some, more than 100 citations were reviewed, whereas others were supported by only a few citations. Nevertheless, the scientific strength of the recommendations was generally very good, as was the degree of agreement with each recommendation among the expert/patient panel.

The recommendations clearly identify several possible targets that could be used in a treat-to-target approach for SLE. Remission should be targeted if at all possible, but prevention of flares, prevention or minimization of damage, reduction of corticosteroid use, and improvements in overall HR-QOL are all identified as reasonable therapy targets. The decision of which target to select at which point in time for each patient will remain the key challenge for the physician taking care of patients with SLE.

The recommendations also provide specific pointers to therapy in general, specifying the important role of immunosuppressive agents in the management of lupus nephritis, the general role of antimalarial agents, the need to address comorbid conditions, and the importance of managing concomitant antiphospholipid syndrome. The recommendations do not direct that specific drugs be used and do not distinguish between "older" and "newer" drugs, or between conventional and biologic agents.

The treat-to-target strategy consists of 3 key elements:

Selection of a therapeutic goal (the target);

Establishing how to measure the goal, and

The intention to change therapy if the target is not achieved.

In the case of SLE, key components of each of these steps are still either lacking or in their infancy. Therefore, the T2T/SLE task force recommended several targets that may be considered for the individual patient, including remission, prevention of flares, reduction in the need for corticosteroids, and prevention or minimization of end-organ damage. Improvement of HR-QOL was seen as a slightly different type of target that may require consideration of the disparate factors that account for impaired HR-QOL.

Measuring targets is a particularly vexing problem in SLE, especially when it comes to measuring disease activity, or in trying to define the absence thereof: remission. With respect to measuring disease activity, organ-specific measurements may be appropriate for patients with a single dominant organ manifestation, such as lupus nephritis. For most patients, however, the combined activity in multiple organs, organ systems, or "domains" must be assessed. Several instruments have been developed for this purpose, including the British Isles Lupus Assessment Group (BILAG) index,[13] the European Consensus Lupus Activity Measurement (ECLAM),[14] and the SLE Disease Activity Index (SLEDAI).[15]

Each of these instruments has been extensively tested, used, and discussed,[16] and each has obvious strengths and weaknesses. Current general recommendations for the management of SLE as well as the specific T2T/SLE recommendations strongly suggest the use of such measures, recognizing their limitations in clinical practice.

Treating to target relies on the availability of therapeutic options that can be administered to achieve the target. The medical armamentarium for patients with SLE remains somewhat limited compared with that for other rheumatologic and autoimmune diseases, but many new drugs are being investigated in late-stage clinical trials at this time. Expectations are high that additional useful therapeutic options will become available in the coming years.[3]


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