Systemic lupus erythematosus (SLE) is a chronic disease that causes inflammation in connective tissues and can impact a variety of body systems resulting in renal, dermatological, cardiovascular, respiratory, digestive, and nervous system clinical presentations. The exact prevalence is difficult to determine because many of the signs and symptoms of SLE resemble those of other disorders. Diagnosis may be delayed for years, and the condition may never be diagnosed in some affected individuals.1
SLE is triggered by the abnormal activation of innate immunity.2 T cell and antigen stimulation leads to hyperactive B cells, which increases production of autoantibodies. As a result, and in conjunction with the inappropriate disposal of apoptotic cellular material, immune complexes form and are deposited throughout the body; these then induce inflammatory reactions and organ damage.3
SLE can affect people young and old, but women are affected far more than men (estimates range from 4-12 women for every 1 man). And women between 15 to 44 years—childbearing age—are at the highest risk of developing SLE. In the United States, minority racial and ethnic groups (eg, Blacks/African Americans, Hispanics/Latinos, Asians, and American Indians/Alaska Natives) are affected more than Whites/Caucasians. While most people with SLE do not have a direct family member with the disease, people with an immediate family member with SLE have only a slightly higher risk for the disease.5
Signs & Symptoms
Signs and symptoms of SLE may include:
Clinical manifestations will vary between patients, as will the frequency and intensity of flares. All SLE patients will experience joint pain and swelling, and roughly half of SLE patients will experience a butterfly-shaped rash over their cheeks and nose. Additional signs and symptoms will also vary between patients depending on which body systems become affected.4
Disease & Clinical Trial Tools
Given the complex multi system nature of lupus, measuring disease activity accurately remains a challenging and demanding task. For instance, lupus is known for its variability both between patients and also in the same patient over time. In addition, clinicians still struggle to define what disease activity means and how it should be measured. Still, several tools have been developed over the years to attempt to create a standardized assessment of disease activity and outcome domains in clinical research. Many assessment tools have been able to detect clinical improvement and have proven reliability, validity, and sensitivity to changes seen in observational studies; some of these tools have also been used in randomized controlled trials. Here are a few of the most common.6
The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and Safety of Estrogens in Lupus National Assessment (SELENA) are pertinent to clinical trial tools.
SLEDAI is a standard scale for evaluating disease activity. The SELENA study modified the original SLEDAI to also encompass ongoing disease activity in rash, mucosal ulcers, and alopecia descriptors. The SLEDAI-2000 (SLEDAI-2K) further added persistent disease activity in proteinuria, and has been proven effective in predicting mortality and disease activity.
Pertinent to clinical trial tools, the Systemic Lupus International Collaborating Clinics (SLICC) criteria for SLE classification identifies 17 criteria, both clinical and immunological.
SLE classification requires:
The British Isles Lupus Assessment Group (BILAG) index assesses disease activity in SLE based on the physician’s “intention to treat.” Pertinent to clinical trial tools, the computerized index scores each of eight organ-based systems with a separate letter score and has proven sensitivity and specificity.
Composite responder indexes combine individual organ and system assessments. The first composite index to be used in randomized controlled lupus trials, the Systemic Lupus Responder Index (SRI) combines the BILAG, SELENA-SLEDAI, and physician global assessment of disease activity (PGA) indexes. Another composite index, the BILAG-based Combined Lupus Assessment (BICLA) includes criteria from the BILAG-2004, SLEDAI-2000, and PGA indexes.
Both pertinent to clinical trial tools, the two indexes are different in that SRI response requires full improvement in some organs while BICLA response requires partial improvement in all organs.12
Pertinent to clinical trial tools, the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) quantifies the activity and damage caused by CLE.
Presenting a more complete clinical picture, the CLASI comprises two scores: