ABSTRACT
The anti-von Willebrand factor nanobody caplacizumab was licensed for adults with immune-mediated thrombotic thrombocytopenic purpura (iTTP) based on prospective controlled trials. However, few data are available on postmarketing surveillance. We treated 90 iTTP patients with a compassionate frontline triplet regimen associating therapeutic plasma exchange (TPE), immunosuppression with corticosteroids and rituximab, and caplacizumab. Outcomes were compared with 180 historical patients treated with the standard frontline treatment (TPE and corticosteroids, with rituximab as salvage therapy). The primary outcome was a composite of refractoriness and death within 30 days since diagnosis. Key secondary outcomes were exacerbations, time to platelet count recovery, the number of TPE, and the volume of plasma required to achieve durable remission. The percentage of patients in the triplet regimen with the composite primary outcome was 2.2% vs 12.2% in historical patients (P = .01). One elderly patient in the triplet regimen died of pulmonary embolism. Patients from this cohort experienced less exacerbations (3.4% vs 44%, P < .01); they recovered durable platelet count 1.8 times faster than historical patients (95% confidence interval, 1.41-2.36; P < .01), with fewer TPE sessions and lower plasma volumes (P < .01 both). The number of days in hospital was 41% lower in the triplet regimen than in the historical cohort (13 vs 22 days; P < .01). Caplacizumab-related adverse events occurred in 46 patients (51%), including 13 major or clinically relevant nonmajor hemorrhagic events. Associating caplacizumab to TPE and immunosuppression, by addressing the 3 processes of iTTP pathophysiology, prevents unfavorable outcomes and alleviates the burden of care.
Subject(s)
Adrenal Cortex Hormones/therapeutic use , Plasma Exchange , Purpura, Thrombotic Thrombocytopenic/therapy , Rituximab/therapeutic use , Single-Domain Antibodies/therapeutic use , ADAMTS13 Protein/blood , Adult , Combined Modality Therapy , Compassionate Use Trials , Disease Progression , Drug Therapy, Combination , Female , Hemorrhage/chemically induced , Historically Controlled Study , Humans , Male , Middle Aged , Platelet Count , Prospective Studies , Purpura, Thrombotic Thrombocytopenic/blood , Purpura, Thrombotic Thrombocytopenic/drug therapy , Purpura, Thrombotic Thrombocytopenic/mortality , Severity of Illness Index , Single-Domain Antibodies/adverse effects , Single-Domain Antibodies/economics , Thromboembolism/etiology , Treatment Outcome , von Willebrand Factor/antagonists & inhibitorsABSTRACT
OBJECTIVE: Autommune diseases could constitute one emerging cause of morbidity in patients infected with human immunodeficiency virus (HIV) due to the chronicity of the infection and to the high level of B cell stimulation induced by HIV. We conducted a cross-sectional study investigating the clinical and biological signs of autoimmunity in HIV infected patients. METHODS: We studied the following plasma immunological variables: antinuclear antibodies (ANA) and antibodies to extractable nuclear antigens, antiphospholipids, anticardiolipins (aCL), antineutrophil cytoplasmic antibodies (ANCA), rheumatoid factor (RF), cryoglobulinemia, total complement, and C4 factor. HIV-RNA, CD4+ cell count, and serological status for hepatitis B (HBV) and C virus (HCV) were also studied. Clinical signs of autoimmune diseases were noted. RESULTS: In total, 97 patients were investigated (men 74%). Median age was 38 years (range 20-64). Median CD4+ count and HIV-RNA were 333/mm3 and 1662 copies/ml, respectively. Coinfection by HBV and HCV was present in 7% and 64% of the patients. In patients with HIV only, we detected cryoglobulinemia in 17% of patients, a positive RF in 19%, ANA > 1/100 in 21%, aCL in 51%, and ANCA > 1/20 in 17% (most of them type C by ELISA). There was a trend for a higher level of cryoglobulinemia and aCL in patients having CD4 lymphocyte counts > 350/mm3 than in others (25% vs 11%, p = 0.26, and 63% vs 42%, p = 0.23, respectively). Patients coinfected with HCV had a higher prevalence of cryoglobulinemia than HCV-free patients (42% vs 17%; p = 0.01). Prevalence of other immunological abnormalities was not different between patients with HIV only and HCV coinfected patients. Thirty patients expressed at least one clinical sign compatible with autoimmune disease. Patients with cryoglobulinemia more often had coinfection with HCV (OR 6.64, 95% CI 1.87-23.57) and IgM > 1.9 g/l (OR 6.16, 95% CI 2.15-17.67). CONCLUSION: Humoral immunological abnormalities are frequent in patients with HIV, but are rarely associated with severe clinical signs.