Have we defined the target?

Efforts to delineate treat to target (T2T) in SLE have been difficult due to disease heterogeneity and lack of biomarkers predicting correctly the disease course and ensuring a safe treatment tapering during quiescence.

The target is disease remission which should be pursued whenever possible. Clinical remission or low disease activity can be realistic goals for which tight monitoring is essential. The patients also require corticosteroid-free intervals while minimizing the risk of disease flare.

Do we have enough arrows to target?

Low disease activity has been studied and implemented and remission has been defined by the Definition of Remission in SLE task force. But the current therapeutic options in SLE are limited. We need far more effective and safer therapies. Biologics and small molecule agents in clinical trials have shown encouraging results but are currently away from reality and the cost is also a matter of concern.

Validation of Lupus Low Disease Activity State (LLDAS) and recent consensus on the final definition of remission in SLE, have provided a direction for the adoption of the T2T strategy in the practice. In reality, even though we try to target remission, prevent organ damage, and improve the quality of life in SLE, the real challenge is heterogeneity. Understanding the natural history of the disease and choosing a meaningful target is important. Prolonged remission on treatment is more attainable than strict remission(off treatment) and associated with reduced damage accrual. A composite outcome measure like LLDAS, defining SLEDAI ≤ 4, PGA ≤1, prednisolone ≤ 7.5 mg, and additional criteria of no new activity, are practically useful.

What is the best T2T approach in Lupus?

The best approach is to meticulously check all the systems and treat them all to prevent a flare with minimum side effects. Hydroxychloroquine (HCQ)has a long onset of action but has long-term safety and prevents SLE flares. All patients should receive HCQ along with VIT D and Calcium supplements.

Lupus Nephritis (LN) is treated with Cyclophosphamide, Mycophenolate, and pulse Methyl Prednisolone for induction of remission and maintenance by Mycophenolate or Azathioprine. For Refractory lupus, Rituximab or IVIg is our choice over plasmapheresis. Tacrolimus and Cyclosporin are used in patients with normal renal function. Challenging issues remain resistant hypertension, anemia, Thrombotic microangiopathy, Cardiorenal failure, and infections.

The Neuropsychiatric manifestations are treated depending on the clinical and neuroimaging findings with immunosuppressants, glucocorticoids, and maintenance by Azathioprine or Mycophenolate. Convulsions, BIH, PRESS, CVA, Encephalopathy, and psychological symptoms like acute depression are just a few events that make you face the battle. Hematological flares are best dealt with Glucocorticoids, G-CSF, and transfusions in crisis. For refractory cytopenia Rituximab or IvIg are preferred. Thrombopoietin receptor agonists like Eltrombopag and Romiplostim are useful in refractory thrombocytopenia. Pulse methylprednisolone followed by Azathioprine or Mycophenolate is preferred for severe Mucocutaneous flares.

Suggested Reading:

1. Martin Aringer et al, Treat to Target in Systemic Lupus Erythematosus, Rheum Dis Clin North America. 2019; 45 : 537–548.
2. Vera Golder and Michel W. P. Tsang-A-Sjoe, Treatment targets in SLE: remission and low disease activity state. Rheumatology 2020; 59 : v19–v28.
3. Roberto Ríos-Garcésa et al, Treat-to-target in systemic lupus erythematosus: Where are we? European Journal of Internal Medicine. 2020; 74 : 29–34.