Treat-to-Target in Lupus, Not an Impossibility, just Exhaustive

The treat-to-target paradigm has been utilized in the management of rheumatoid arthritis, diabetes and hypertension.

“The paradigm that has been shown in other diseases is that if we have measurable goals for therapy, people tend to have better outcomes,” said Maria Dall’Era, M.D., a rheumatologist and director of the Lupus Clinic at the UCSF Medical Center.  “We need efficacious, safe therapies to make treat-to-target a real possibility.”

It is time for rheumatologists to consider bringing the treat-to-target paradigm into lupus management, she said.

“Lupus is quite difficult because lupus is very heterogeneous - so what is the target going to be? If the patient has arthritis, one of the targets is improvement in arthritis. If a patient has rash, the target will be different. The targets vary for different people. All that has to be worked out:  What is the target in lupus patients going to be?” Dr. Dall’Era said highlighting a few potential targets:  Flare prevention, prevention of accrual of tissue damage and aiming for the lowest possible glucocorticoid dose.

Another is the consensus definition of Lupus Low Disease Activity State, she was quick to add.⁽²⁾  A recent study has shown that patients who achieve low disease activity state, experience less organ damage accrual and fewer flares than other patients more than half of the time, she said.⁽²⁾[[{"type":"media","view_mode":"media_crop","fid":"46527","attributes":{"alt":"Maria Dall’Era, M.D.","class":"media-image media-image-right","id":"media_crop_4749117076862","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"5404","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"font-size: 13.008px; line-height: 1.538em; float: right;","title":"Maria Dall’Era, M.D.","typeof":"foaf:Image"}}]]

“One issue here for lupus is that we are usually able to achieve a state of low disease activity if we use high enough doses of steroids. The problem is, that’s not acceptable because the damage that is induced by steroids can outweigh any issues the patient might have from residual lupus arthritis, for example. So we have to attain that state of low disease activity without using high doses of glucocorticoids that will then lead to their own damage. It’s a fine balance,” Dr. Dall’Era said.

That is why one defining criterion for the Lupus Low Disease Activity Stateis that a patient’s prednisone dose must be low while the other criteria are achieved, she said. 

A study published in Oct. 12, 2015 issue of Annals of the Rheumatic Diseases, defined Lupus Low Disease Activity State (LLDAS) as:

(1) SLE Disease Activity Index (SLEDAI)-2K ≤4, with no activity in major organ systems (renal, central nervous system (CNS), cardiopulmonary, vasculitis, fever) and no haemolytic anaemia or gastrointestinal activity;

(2) no new lupus disease activity compared with the previous assessment;

(3) a Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-SLEDAI physician global assessment (scale 0–3) ≤1;

(4) a current prednisolone (or equivalent) dose ≤7.5 mg daily;

(5) well tolerated standard maintenance doses of immunosuppressive drugs and approved biological agents.

“I envision a time when there will be guidelines released that help guide the clinician in categorizing patients by specific organ manifestations. For example, if you have a patient with lupus arthritis, ‘follow these guidelines.’ If your patient has rash, ‘do this.’ With nephritis, ‘do this,’” Dr. Dall’Era said.

But the patient has an equally important role in treating lupus. Patient acceptance and understanding will be crucial for effective implementation of treat-to-target strategies, she said.

“I think guidelines have to be ‘married’ to the needs of the individual patient and the patient’s wishes. Maybe a patient would rather live with a little bit of arthritis from lupus and not have to escalate their immunosuppressive therapy. Or, they might be willing to live with a little bit of rash. The patient’s preference is incredibly important as a part of this. The patient has to weigh in because at the end of the day, medications all have toxicities associated with them. We can’t give people toxicities in the quest for completely getting rid of symptoms - that’s not realistic,” Dr. Dall’Era said.

References:

Dall’Era M. "Update on biologic therapy in SLE: the old and the new."  2016 American College of Rheumatology Winter Rheumatology Symposium presentation. January 23-29, 2016. Snowmass Village, Colorado.

Franklyn K, Lau CS, Navarra SV, et al. "Definition and initial validation of a Lupus Low Disease Activity State (LLDAS)." Annals of the Rheumatic Diseases. 2015. doi:10.1136/annrheumdis-2015-207726.