Experts Seek Simpler Endpoints for Lupus Trials

Janis C. Kelly

January 13, 2020

Difficulties in measuring changes in systemic lupus erythematosus (SLE) disease activity over time have had a bearing on clinical trial design as well as clinical care and may be a factor in recent problems interpreting trials of potential new lupus drugs.

Now researchers say two visual analogue scales — the SELENA SLEDAI Physician's Global Assessment (SSPGA) and the Lupus Foundation of America-Rapid Evaluation of Activity in Lupus (LFA-REAL) — are reliable surrogates that could be used as continuous or dichotomous response measures instead of more difficult to use common SLE trial endpoints.

"Additionally, LFA-REAL can provide individualised scoring at the symptom or organ level," the researchers write.

An expert challenges those findings, however, and says the researchers failed to consider an already validated scoring tool, the Hopkins UCSF Lupus Activity Index.

Rheumatologist Aikaterini Thanou, MD, and colleagues conducted a Bristol-Myers Squib–funded comparison of four SLE assessment tools. Thanou, from Oklahoma Medical Research Foundation, Oklahoma City, and colleagues report their findings in an article published online December 30 in Lupus Science and Medicine.

They compared the SSPGA and the LFA-REAL with the SLE Responder Index (SRI), the SLE Disease Activity Index (SLEDAI), the British Isles Lupus Assessment Group Index 2004 (BILAG 2004), the Cutaneous Lupus Area and Severity Index (CLASI), and the BILAG-Based Combined Lupus Assessment (BICLA).

The researchers used data from the Clarification of Abatacept Effects in SLE With Integrated Biologic and Clinical Approaches clinical trial (the ABC Study) prior to unblinding to compare outcome measures regardless of treatment assignment. The study included 50 patients who were assessed at a screening visit and at monthly visits for a period of up to 12 months. Participants also underwent up to two follow-up visits 2 and 4 months after study completion. They underwent an average of 10.6 visits. All patients had at least moderately active arthritis at study entry; 29 had active mucocutaneous features, but none had active cardiopulmonary, renal, or significant hematologic involvement.

At entry, the average disease activity scores were as follows: SLEDAI, 6.8; BILAG, 10.5; SPGA, 53 mm; and LFA-REAL, 71 mm.

Changes in disease activity, which were assessed in 478 visit pairs, showed that SSPGA and LFA-REAL correlated with each other (r = 0.936). In addition, SSPGA correlated with SLEDAI (r = 0.742) and BILAG (r = 0.776), and LFA-REAL correlated with SLEDAI (r = 0.778) and with BILAG (r = 0.813) (all P < .0001).

"Changes in SSPGA and LFA-REAL strongly correlated with SRI-4 [SLE Responder Index–4 ] and BICLA by receiver operating characteristic analysis (P < .0001 for all). Additionally, LFA-REAL correlated to individual BILAG organ scores (musculoskeletal: r = 0.842, mucocutaneous: r = 0.826 (P < .0001 for both)," the authors explain.

The analysis also provided proof of concept that data from the simple VAS scoring that was used "can be calibrated to accepted outcome measures," they continue.

However, rheumatologist Michelle A. Petri, MD, MPH, told Medscape Medical News the researchers overlooked the Hopkins UCSF Lupus Activity Index, which uses the same VAS as LFA-REAL for disease activity globally and for each organ system.

Petri, who developed the Hopkins UCSF Lupus Activity Index in 1992 with David Hellmann, MD, and Marc Hochberg, MD, noted that it was validated many years ago.

"The Hopkins UCSF Lupus Activity Index has been used for routine clinical use for many decades. The LFA-REAL is a small change in that assessment," Petri said.

Petri is director of the Hopkins Lupus Center and professor of medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.

"Basically, I agree that VAS are helpful in routine clinical practice. It is much harder to use VAS in clinical trials, where it might not be the same physician each time grading the patient," she warned.

The researchers propose that a prospective validation study might pinpoint the changes in LFA-REAL "that reflect the gold standard of physicians' opinion, while assessing patients in real-time in the clinic."

The study was supported by Bristol-Myers Squibb. The authors and Petri have disclosed no relevant financial relationships.

Lupus Sci Med. Published online in the December 30, 2019. Full text

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