Cost-effectiveness analysis of treatments for the first episode of catastrophic antiphospholipid syndrome: A study based on the catastrophic antiphospholipid syndrome registry.

BACKGROUND: Treatments for catastrophic antiphospholipid syndrome (CAPS) rose from recommendations and consensus of international experts based on case series or case reports. We aimed to evaluate the treatment scheme with the best cost-effectiveness ratio associated with lower mortality as a high-impact clinical benefit. METHODS: The CAPS Registry was used as our source of structured data on the different therapeutic strategies, their frequency, and their effectiveness (survival). Starting from around 50 different schemes, we identified those with a mortality of less than 33% within the 18 most frequently utilized. After applying the efficiency frontier method, we included two schemes to conduct a cost-effectiveness analysis from the Colombian healthcare sector perspective. Scheme 1 (Glucocorticoids + Anticoagulation + Anti-aggregation + Intravenous IgG immunoglobulin) and scheme 2 (Glucocorticoids + Anticoagulation + Anti-aggregation + Plasma exchange) were compared in terms of costs and survival. Deterministic and probabilistic sensitivity analyses (Monte Carlo simulation) were conducted to evaluate model robustness and uncertainty. RESULTS: Our analysis uses the information corresponding to 427 cases from the CAPS registry, the majority being women (68.8%), with a mean age of 45.7 years and bearing general mortality of 38.17% (female: 38.4%, male: 37.5%). Scheme 2 was the cost-effective strategy over scheme 1. The results were robust on discrete sensitivity analysis and probability sensitivity analysis (Monte Carlo simulation). CONCLUSION: To our knowledge, this is the first economic evaluation focused on the treatment of CAPS. For the Colombian health system, schemes 1 and 2 have similar behavior; nevertheless, scheme 2 represents the best cost-effectiveness ratio. This treatment approach is highly susceptible to the allocation of resources by the system and beneficial in terms of health outcomes.

Successful treatment of refractory secondary immune thrombocytopenia (antiphospholipid antibody syndrome-associated) with the combination of rituximab and romiplostim at the cost of severe bone pain: A case report and review of literature.

INTRODUCTION: Immune thrombocytopenia is an autoimmune disorder associated with increased thrombocyte destruction and impaired production in the bone marrow. Proposed mechanisms include an antibody or autoreactive T-cell-associated autoimmunity and thrombopoietin deficiency among others. Clinical manifestations are predominantly mucocutaneous hemorrhages including petechiae, purpura, mucosal bleeding in the urinary or the gastrointestinal tracts, menorrhagia, and epistaxis. The purpose of the treatment is to prevent bleeding rather than normalizing the platelet counts. First-line treatments include corticosteroids ± intravenous immunoglobulin and Anti-D which mainly decrease antibody-mediated platelet destruction and increase the number of peripheral Tregs. Second-line and subsequent therapies include splenectomy, chimeric anti-CD20 antibody (rituximab), which eliminates B cells and act as an immunomodulatory agent, and Thrombopoietin receptor agonists (romiplostim), which promote platelet production. CASE REPORT: We describe a 40-year-old male patient diagnosed with immune thrombocytopenia that was refractory to first-line corticosteroid and intravenous immunoglobulin and second-line romiplostim monotherapy treatments.Management and outcome: The patient was given the romiplostim and rituximab combination which not only successfully treated thrombocytopenia but also resulted in grade 3 bone pains and the patient's subsequent refusal to continue therapy. DISCUSSION: Common adverse effects of rituximab are infusion reactions and prolonged immunosuppression; those of romiplostim include thrombosis, headaches, arthralgia-myalgia, and gastrointestinal symptoms. This case shows that romiplostim has not caused any discernible side effects when given alone, while combination with rituximab resulted in severe bone and joint pains. We hypothesize that this combination regimen shows a synergistic effect both in terms of efficacy and adverse-effect probability and/or severity.

Oral anticoagulation cost in primary antiphospholipid syndrome: comparison between warfarin and hypothetical rivaroxaban.

: The objective of the study is to perform a cost comparison of 1 year of oral anticoagulation management with warfarin vs. hypothetical rivaroxaban (RRX) in thrombotic primary antiphospholipid syndrome. Longitudinal study on 20 primary antiphospholipid syndrome patients followed-up for 1 year after anticoagulation stabilisation with warfarin: a dedicated software calculated number of clinic visits, time in therapeutic range and warfarin consumption for each patient; for RRX, we considered a visit every 3 months (baseline done in hospital before attending anticoagulant clinic); knowing the cost of both anticoagulants, the laboratory cost and the human cost we calculated and compared the yearly expenditure. Average time in therapeutic international normalized ratio range was 69 ±â€Š11%: warfarin management required a total of 375 of visits compared with the 60 for RRX; the yearly cost of RRX was superior to that of warfarin (12 012 vs. 446.4 euros, P < 0.0001), and in spite of lower laboratory (738 vs. 1853 euros, P < 0.0001) and human costs (774.6 vs. 4841 euros), RRX thromboprophylaxis still yielded a hefty bill (13 525 vs. 7140 euros, P < 0.0001). Switching from warfarin to RRX will be 48% more expensive to our Healthcare Authority; unless ongoing clinical trials demonstrate improved long-term outcomes for RRX over warfarin, we feel that a 69% time in therapeutic range does not warrant a change to RRX at a 48% increased cost.

Quality of life in patients with antiphospholipid syndrome is related to disease burden and anticoagulant therapy.

AIM: To evaluate health-related quality of life (HRQoL) in primary antiphospholipid syndrome (PAPS) and correlate it with a crude estimate of accrual organ damage, comorbidity (diabetes mellitus, hypertension and dyslipidemia) and treatment (oral anticoagulation, immunosuppressors and prednisone). METHODS: We assessed HRQoL with the Short-Form 36 (SF-36) and the Lupus Quality of Life instrument (LupusQoL) and the disease burden with a modified Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR SDI). As controls we used SF-36 data from a Mexican general population within the same age range. RESULTS: We included 50 PAPS patients (86% women), mean age 47.6 ± 14.5 years, median disease duration 9.4 years, median SLICC/ACR score of 1 point and 80% had thrombotic events. PAPS patients had lower HRQoL than controls. We found a positive correlation between SF-36 and LupusQoL (r = 0.85, P < 0.0001). The SLICC/ACR SDI correlated negatively with both LupusQoL and SF-36, specifically the peripheral vascular domain (r = -0.29, P = 0.03, for both). Patients on oral anticoagulants (n = 37) had lower LupusQoL, physical functioning, intimate relationships, burden to others and pain scores as well as a lower SF-36 physical functioning score. We did not find differences in HRQoL regarding comorbidities and other treatments. CONCLUSIONS: HRQoL in PAPS was related to burden of the disease specifically at the vascular peripheral area and use of anticoagulants.

Obstetric antiphospholipid syndrome.

Antiphospholipid syndrome (APS) in pregnancy has a serious impact on maternal and fetal morbidity. It causes recurrent pregnancy miscarriage and it is associated with other adverse obstetric findings like preterm delivery, intrauterine growth restriction, preeclampsia, HELLP syndrome and others. The 2006 revised criteria, which is still valid, is used for APS classification. Epidemiology of obstetric APS varies from one population group to another largely due to different inclusion criteria and lack of standardization of antibody detection methods. Treatment is still controversial. This topic should include a multidisciplinary team and should be individualized. Success here is based on strict control and monitoring throughout pregnancy and even in the preconception and postpartum periods. Further research in this field and unification of criteria are required to yield better therapeutic strategies in the future.

Anticuerpos antifosfolípidos. Valoración clínica actual / Antiphospholipid antibodies. Current clinical assessment

El síndrome anticuerpo antifosfolipido (SAF) constituye una enfermedad autoinmune que se caracteriza por presentar trombosis vascular y abortos recurrentes, asociada a la elevación persistente de anticuerpos antifosfolípidos séricos. Los eventos trombóticos pueden ocurrir tanto en las arterias y venas como en la microcirculación. Las manifestaciones clínicas dermatológicas más frecuentes son livedo reticularis, vasculitis livedoide y úlceras, entre otras. En este trabajo se actualizan los conceptos de su etiología y los criterios diagnósticos corregidos desde el año 2004. Además se plantea un algoritmo diagnóstico y las pautas de tratamiento actuales.

The relation between antiphospholipid syndrome-related pregnancy morbidity and non-gravid vascular thrombosis: a review of the literature and management strategies.

The antiphospholipid syndrome (APS) is associated with pregnancy morbidity and vascular thrombosis in the presence of circulating antiphospholipid (aPL) antibodies. Clinical manifestations of aPL antibodies represent a spectrum (asymptomatic, pregnancy events, vascular events, or both pregnancy and vascular events), and APS should not be considered a single disease with a predictable outcome. Patients with aPL antibodies are at increased risk of vascular thrombotic events during pregnancy, the postpartum period, and even during long-term follow-up after an APS-related pregnancy event. Therefore, the purpose of this paper is to review the relation between APS-related pregnancy morbidity and vascular thrombosis, and to address the importance of prophylactic therapy during and after APS pregnancies to prevent maternal thrombotic complications. During pregnancy, low-dose aspirin (LDA) should be considered for all patients with aPL antibodies and heparin should be added to LDA in patients fulfilling the Sapporo criteria for definite APS. During delivery, especially with caesarian section, periods without anticoagulation should be kept to an absolute minimum. Some data suggest that LDA might be effective against future non-gravid vascular thrombosis in patients with APS and a history of only pregnancy morbidity.

Longterm anticoagulation is preferable for patients with antiphospholipid antibody syndrome. result of a decision analysis.

OBJECTIVE: Patients with antiphospholipid antibody syndrome (APS) have a high risk for rethrombosis. Anticoagulation with warfarin and aspirin reduces the frequency of recurrences. No universally accepted approach regarding the duration and intensity of antithrombotic therapy exists. We investigated the best antithrombotic regimen for patients with APS after the first deep venous thrombosis (DVT). METHODS: We identified 6 anticoagulation regimens used in such patients, the rates of morbidity and mortality associated with bleeding, and the rates of recurrent thrombosis associated with APS by literature search. A decision tree was developed and the expected risks and benefits of each anticoagulation regimen were assessed at 2 different time points: at one year and again 4 years after the initial thrombosis. RESULTS: Based on the decision analysis, longterm warfarin alone at an international normalization ratio (INR) between 3.0 and 4.0 had the highest expected utility of the 6 antithrombotic regimens, both one year and 4 years after the initial venous thrombotic event. Short term anticoagulation for only 6 months is less beneficial. Combination therapy of warfarin and aspirin (ASA) does not offer an improvement in the expected utility over warfarin alone. CONCLUSION: Although the applicability of this analysis to clinical decision-making is not entirely clear, patients with APS presenting with DVT appear to benefit from longterm warfarin (INR 3.0-4.0) that may be superior to warfarin (INR 2.0-3.0). Short term warfarin therapy seems to be less beneficial and the use of ASA does not offer a clear additional benefit. Randomized controlled trials are needed to provide a better basis for recommendations for the treatment APS.