SLICC PI: DR. JOHN G. HANLY

An international, multi-center, prospective, inception cohort study of neuropsychiatric systemic lupus erythematosus (NPSLE)

Funding Source: Canadian Institute for Health Research

The primary objective of this study is to define (1). The long-term significance of NP events attributed to SLE and non-SLE causes in the SLICC inception cohort using patient self-report health-related quality of life (HRQOL), physician assessment; (2). The recurrence of NP events; (3). The cumulative organ damage they may cause; and (4). Their impact on mortality. Secondary objectives are (1). To determine the association between previously characterized and novel autoantibodies with clinical NP events attributed to SLE and non-SLE causes and (2). To identify the clinical and laboratory predictors of NP events and NP damage in SLE patients using regression and multi-state statistical models.

As of July 2017, 10 publications have emanated from this effort. In short, 28% of patients experienced at least one NP event at the time of diagnosis although most them could not be attributed to lupus. Clinically distinct NP events attributed to lupus were found to be associated to anti-P antibodies and the Lupus anticoagulant (LAC). On follow up, these antibodies were associated with an increased risk of intracranial thrombosis and lupus psychosis, respectively. The short-term outcomes of NP events were determined by both, the characteristics of the events and their attribution, with NP events attributed to lupus having a better outcome than those that were not; however, both types of events affected HRQOL as measured by the mental and physical capacity scores (MCS and PCS) of the SF-36. In fact, the MCS and sub-scales scores are strongly associated with the clinical outcome of NP events in SLE patients.

Specific NP events that have been examined so far include seizure disorders, headache and mood disorders. In terms of seizures, they primarily occur close to the diagnosis of SLE, in African descendants, of low socioeconomic status and in patients who already have some organ damage. Most seizures resolve without lasting impact on the patients’ HRQOL. Antimalarials are protective of their occurrence. In terms of headache, it is a relatively common occurrence in SLE, but overall it is not associated with global disease activity; although headaches are associated with lower HRQOL, they tend to resolve over time independent of lupus-specific therapies. Finally, in terms of mood disorders, they tend to be multifactorial in origin, they affect HRQOL but are not associated with disease activity, autoantibodies or organ damage. They respond to non-specific lupus therapies.
In short, the SLICC cohort is a very valuable resource which is permitting the evaluation of common and uncommon NP events, their significance and outcome. Over the ensuing years, as follow of these patients continues, valuable additional information will certainly be obtained.

References:

  • 1.Hanly JG, Urowitz MB, O’Keeffe AG, Gordon C, Bae SC, Sanchez-Guerrero J, Romero-Diaz J, Clarke AE, Bernatsky S, Wallace DJ, Ginzler EM, Isenberg DA, Rahman A, Merrill JT, Petri M, Fortin PR, Gladman DD, Fessler BJ, Alarcón GS, Bruce IN, Dooley MA, Steinsson K, Khamashta MA, Ramsey-Goldman R, Manzi S, Sturfelt GK, Nived O, Zoma AA, van Vollenhoven RF, Ramos-Casals M, Aranow C, Mackay M, Ruiz-Irastorza G, Kalunian KC, Lim SS, Inanc M, Kamen DL, Peschken CA, Jacobsen S, Theriault C, Thompson K, Farewell V. Headache in systemic lupus erythematosus: results from a prospective, international inception cohort study. Arthritis Rheum. 2013 Nov;65(11):2887-97. doi: 10.1002/art.38106. PMID: 24166793
  • 2.Hanly JG, Urowitz MB, Su L, Gordon C, Bae SC, Sanchez-Guerrero J, Romero-Diaz J, Wallace DJ, Clarke AE, Ginzler E, Merrill JT, Isenberg DA, Rahman A, Petri M, Fortin PR, Gladman D, Bruce IN, Steinsson K, Dooley M, Khamashta MA, Alarcón GS, Fessler BJ, Ramsey-Goldman R, Manzi S, Zoma AA, Sturfelt GK, Nived O, Aranow C, Mackay M, Ramos-Casals M, van Vollenhoven R, Kalunian KC, Ruiz-Irastorza G, Lim S, Kamen DL, Peschken CA, Inanc M, Theriault C, Thompson K, Farewell V. Seizure disorders in systemic lupus erythematosus results from an international, prospective, inception cohort study. Ann Rheum Dis. 2012 Sep;71(9):1502-9. doi: 10.1136/annrheumdis-2011-201089. PMID: 22492779
  • 3.Hanly JG, Urowitz MB, Su L, Gordon C, Bae SC, Sanchez-Guerrero J, Romero-Diaz J, Wallace DJ, Clarke AE, Ginzler E, Merrill JT, Isenberg DA, Rahman A, Petri M, Fortin PR, Gladman D, Bruce IN, Steinsson K, Dooley M, Khamashta MA, Alarcón GS, Fessler BJ, Ramsey-Goldman R, Manzi S, Zoma AA, Sturfelt GK, Nived O, Aranow C, Mackay M, Ramos-Casals M, van Vollenhoven R, Kalunian KC, Ruiz-Irastorza G, Lim S, Kamen DL, Peschken CA, Inanc M, Theriault C, Thompson K, Farewell V. Seizure disorders in systemic lupus erythematosus results from an international, prospective, inception cohort study. Ann Rheum Dis. 2012 Sep;71(9):1502-9. doi: 10.1136/annrheumdis-2011-201089. PMID: 22492779
  • 4.Hanly JG, Urowitz MB, Su L, Bae SC, Gordon C, Clarke AE, Bernatsky S, Vasudevan A, Isenberg DA, Rahman A, Wallace DJ, Fortin PR, Gladman D, Romero-Diaz J, Sanchez-Guerrero J, Dooley MA, Bruce IN, Steinsson K, Khamashta M, Manzi S, Ramsey-Goldman R, Sturfelt G, Nived O, van Vollenhoven RF, Ramos-Casals M, Aranow C, Mackay M, Kalunian KC, Alarcón GS, Fessler BJ, Ruiz-Irastorza G, Petri M, Lim SS, Kamen DL, Peschken CA, Farewell V, Thompson K, Theriault C, Merrill JT. Autoantibodies as biomarkers for the prediction of neuropsychiatric events in systemic lupus erythematosus. Ann Rheum Dis 2011;70:1726–1732. doi:10.1136/ard.2010.148502. PMID: 21893582
  • 5.Hanly JG, Urowitz MB, Sanchez-Guerrero J, Bae SC, Gordon C, Wallace DJ, Isenberg DA, Alarcón GS, Clarke AE, Bernatsky S, Merrill JT, Petri M, Dooley MA, Gladman D, Fortin PR, Steinsson K, Bruce IN, Manzi S, Khamashta MA, Zoma AA, Aranow C, Ginzler EM, van Vollenhoven RF, Font J, Sturfelt G, Nived O, Ramsey-Goldman R, Kalunian KC, Douglas J, Thompson K, Farewell V for the Systemic Lupus International Collaborating Clinics. Neuropsychiatric Events at the Time of Diagnosis of Systemic Lupus Erythematosus An International Inception Cohort Study. Arthritis Rheum. 2007 Jan; 56(1):265-273. Doi: 10.1002/art.22305. PMID: 17195230

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