Antiphospholipid Syndrome at the ACR 2011

There have three studies addressing the subject of antiphospholipid syndrome (APS), that are interesting to show. There were some more, that I don’t show as I’m already stretching the criterium interesting.






Antiphospholipid Syndrome Patients and Coenzyme Q Treatment


Chary Lopez-Pedrera and colleagues studied oxidative stress and its role in the pathophysiology of APS by analyzing mitochondrial function, which was measured by mitochondrial membrane potential (MMP) with flow cytometry. Mitochondrial dynamics in monocytes treated with aPL-IgG in the presence or in the absence of CoQ10 was studied. “CoQ10 decreased significantly the percentage of cells with altered MMP as well as the production of ROS and aPL-IgG-induced production of peroxides. CoQ10 treatment also affected significantly the aPL-IgG induced expression of TF, VEGF and Flt1, as well as the intracellular signalling pathways regulating their expression.” Look for the conclusion of the study below. My own conclusion is that CoQ10 might prevent monocyte activation in patients with APS. And – reducing oxidative stress might also be a good idea, e.g. quit smoking.


[SUN] 725
Mitochondrial Dysfunction in Monocytes From Antiphospholipid Syndrome Patients: Implications in the Pathogenesis of the Disease and Effects of Coenzyme Q Treatment.
Chary Lopez-Pedrera1, Carlos Perez-Sanchez1, Patricia Ruiz-Limon1, Ma Angeles Aguirre1, Rosario Ma Carretero1, Nuria Barbarroja1, Antonio Rodriguez-Ariza1, Eduardo Collantes-Estevez1, Jose Antonio Gonzalez-Reyes2, Jose Manuel Villalba2, Francisco Velasco1, Munther A. Khamashta3, Maria Laura Bertolaccini3 and Ma Jose Cuadrado4.
1IMIBIC-Reina Sofia Hospital, Cordoba, Spain, 2University of Cordoba, Cordoba, Spain, 3Lupus Research Unit, The Rayne Institute, Kings College London School of Medicine, London, United Kingdom, 4The Rayne Institute, London, United Kingdom
Conclusion: The binding of aPL-IgG to monocytes membrane elicites a redox-signalling pathway in which mitochondrial activity is compromised, and dynamics is altered towards enhanced rates of mitochondrial fission. The induced mitochondrial dysfunction, which is prevented by CoQ10, seems to be directly involved in the aPL-induced monocyte activation.




Effects of Fluvastatin on Pro-Inflammatory and Pro-Thrombotic Markers in Antiphospholipid Antibody (aPL)-Positive Patients

Vijaya L. Murthy and colleagues studied “the effects of fluvastatin on pro-inflammatory and pro-thrombotic biomarkers in persistently aPL-positive patients.” The following biomarkers showed a statistically significant reduction compared to baseline (p<0.0001): IL-6, IL-1-beta, TNF-alpha, sTF, sICAM-1, sVCAM-1 and E-selectin. Other biomarker didn’t show a statistically significant reduction compared to baseline (p<0.0001): IL-8, VEGF, IP10, sCD40L, INF-alpha2. Fluvastatin showed a signicicant reduction of pro-inflammatory and prothrombotic biomarkers patients with APS.




[SUN] 726
Effects of Fluvastatin on Pro-Inflammatory and Pro-Thrombotic Markers in Antiphospholipid Antibody (aPL)-Positive Patients: Preliminary Results from an Open-Label Prospective Pilot Study.
Vijaya L. Murthy1, Doruk Erkan2, Praveen Jajoria1, Rohan Willis1, JoAnn Vega2, Giuseppe Barilaro1, Gurjot Basra1, Elizabeth Hsu1, Laura Aline Martinez-Martinez1, Shraddha Jatwani1, Elizabeth Papalardo1, Emilio B. Gonzalez1, Prashanth R. Sunkureddi3 and Silvia S. Pierangeli1.
1University of Texas Medical Branch, Galveston, TX, 2Barbara Volcker Center for Women and Rheumatic Diseases,
Hospital for Special Surgery, New York, NY, 3The University of Texas Medical Branch, Nassau Bay, TX
samples, fluvastatin significantly reduced IL6, IL1_, TNF_, sTF, sICAM-1, sVCAM, and sE-sel levels within 30–90 days of treatment (Table). There was no significant change in aCL or a_2GPI titers.
Conclusion: Based on the preliminary analysis of our ongoing pilotstudy, fluvastatin 40 mg daily for 3 months significantly reduced the or without SLE. These findings: a) underscore the importance of identifying aPL-related disease biomarkers; and b) provide further support for the potential beneficial effects of statins in aPL-positive patients justifying future controlled clinical studies.



Rituximab in Antiphospholipid Syndrome (RITAPS)

Doruk Erkan and colleagues studied rituximab in antiphospholipid syndrome. “The primary objective of this pilot, open-label, Phase II study was to evaluate the safety of rituximab in 20 aPL-positive patients, as assessed by serious and non-serious adverse events (AE) (up to 12 months [m]).” Two patients out of 19 developed infusion reactions, which I think is a high number; the study does not reflect about the issue of a special risk. They counted 59 AEs (12 serious with hospitalizations, but interpreted these as “unlikely” to be related to rituximab, 7 non-serious within 48h of infusion were interpreted as “likely”. Even if unrelated to rituximab is correct, I’ve never seen as many AEs, especially with hospitalization is my own patients (rheumatoid arthritis), so I think that this is another hint to look into special risks for aPL-positive patients treated with rituximab. There were some effects on aPL-tests, but not convincing as the largest effects are in the smallest groups (down to n=2). In the aCL IgM group (n=5) we may look at the results: 20/20/60 (4 weeks), 20/20/60 (16 weeks), 25/25/50 (24 weeks, 1 drop-out), 33/33/33 (52 weeks, 2 drop-outs) [all: complete respense/partial response/no response in %]. I think with 40% drop-out in a year and the small size of groups it’s hardly convincing to draw conclusions. The largest group of patients has been the lupus anticoagulant group with n=17 and they showed 100% no response. The authors concluded that “safety appears to be consistent with rituximab’s known safety profile” “B cell depletion appears to be effective in controlling some aPL manifestations during 6m of follow-up”.


I have been pondering quite a while if we really need this study as the effects aren’t convincing and I think that there are safety issues. The study leaves open the question, why aPL-positive patients should be treated with a biologic at all. Out of ethic concerns think it’s better to stop this ongoing study.



[SUN] 727
Rituximab in Antiphospholipid Syndrome (RITAPS)—A Pilot Open-Label Phase II Prospective Trial for Non-Criteria Manifestations of Antiphospholipid Antibodies (aPL).
Doruk Erkan1, JoAnn Vega2, Glendalee Ramon2, Elizabeth Kozora3 and Michael D. Lockshin2.
1Barbara Volcker Center for Women and Rheumatic Diseases, Hospital for Special Surgery, New York, NY, 2Barbara Volcker Center for Women and Rheumatic Diseases: Hospital for Special Surgery, New York, NY, 3National Jewish Health, Denver, CO
Conclusion: Based on the preliminary analysis of our ongoing pilot study of rituximab-receiving aPL-positive patients with non-criteria aPL manifestations: a) safety appears to be consistent with rituximab’s known safety profile although 11% of our patients could not complete the treatment protocol due to reactions; b) B cell depletion appears to be effective in controlling some aPL manifestations during 6m of follow-up; and c) no substantial change in aPL profiles was observed in patients who completed 12m of follow-up.



Effects of Maximal Acute Physical Exercise on Prothrombin Time in Patients with Primary Antiphospholipid Syndrome


Carolina B. Garcia and olleagues were interested to evaluate “the effect of acute physical exercise on prothrombin time (PT) in patients with primary antiphospholipid syndrome under oral anticoagulation therapy with warfarin.” But they fail to tell us, why they are interested in this question or if any effect of physical exercise on anticoaluation would have been to be expected. But now we know that physical exercise doesn’t change prothrombin time in patients with primary antiphospholipid syndrome.


OT: The authors abbreviate primary antiphospholipid syndrome as PAPS, which is already elsewhere in use.


[MON] 1572
Effects of Maximal Acute Physical Exercise on Prothrombin Time in Patients with Primary Antiphospholipid Syndrome (PAPS) Under Oral Anticoagulation with Warfarin and Exercise Capacity.
Carolina B. Garcia1, Luciana N. J. Matos2, Carlos E. Negrao2, Hamilton Roschel3, Ana Lucia S. Pinto4, Jozelio F. Carvalho5, Eloisa Bonfa6 and Fernanda R. Lima1.
1Rheumatology Department, Sao Paulo, Brazil, 2University of Sao Paulo, InCor, Sao Paulo, Brazil, 3University of Sao Paulo, School of Physical Education and Sport, Sao Paulo, Brazil, 4University of Sao Paulo, School of Medicine, Rheumatology Division, LACRE, Sao Paulo, Brazil, 5Faculdade de Medicina da Universidade de Sa˜o Paulo, Sa˜o Paulo, Brazil, 6Faculdade de Medicina da Universidade de Sa˜o Paulo (FMUSP), Sao Paulo, Brazil
Conclusion: This is the first study to demonstrate that an acute exercise bout of maximal intensity is safe and did not affect PT in patients with primary antiphospholipid syndrome under oral coagulation therapy with warfarin.