Myeloproliferative neoplasms and clonal haematopoiesis in patients with giant cell arteritis: a case-control and exploratory study.

OBJECTIVES: GCA is a large vessel vasculitis for which triggering factors remain unknown. Clonal haematopoiesis (CH) was associated with atherosclerosis through the induction of inflammation in myeloid cells, and data suggest that CH expansion and inflammation may support each other to induce a pro-inflammatory loop. Our objective was to describe the impact of JAK2p.V617F-mutated myeloproliferative neoplasms (MPNs) on GCA and to screen MPN-free patients for CH mutations. METHODS: We performed a retrospective case-control study comparing the characteristics of 21 GCA patients with MPN and 42 age- and gender-matched GCA patients without MPN. Also, 18 GCA patients were screened for CH through next-generation sequencing (NGS). RESULTS: The most frequent associated MPN was essential thrombocythaemia (ET; n = 11). Compared with controls, GCA patients with MPN had less-frequent cephalic symptoms (71.4 vs 97.6%; P = 0.004) and higher platelet counts at baseline [485 × 109/l (interquartile range 346-586) vs 346 (296-418); P = 0.02]. There was no difference between groups for other clinical features. Overall survival was significantly shorter in patients with MPN compared with controls [hazard ratio 8.2 (95% CI 1.2, 56.6); P = 0.03]. Finally, screening for CH using NGS in 15 GCA patients without MPN revealed CH in 33%. CONCLUSION: GCA patients with MPN display higher platelet counts and shorter overall survival than controls. This association is not fortuitous, given the possible pathophysiological relationship between the two diseases. CH was found in one-third of GCA patients, which may be higher than the expected prevalence for a similar age, and should be confirmed in a larger cohort.

Efficacy and safety of TNF-α antagonists and tocilizumab in Takayasu arteritis: multicentre retrospective study of 209 patients.

OBJECTIVE: To assess the safety and the efficacy of TNF-α antagonists and tocilizumab in patients with Takayasu arteritis (TAK). METHODS: A total of 209 patients with TAK [median age 29 years (interquartile range 7-62)], 186 (89%) females] were included. They received either TNF-α antagonists [n = 132 (63%) with 172 lines; infliximab (n = 109), adalimumab (n = 45), golimumab (n = 8), certolizumab (n = 6) and etanercept (n = 5)] or tocilizumab [n = 77 (37%) with 121 lines; i.v. and s.c. in 95 and 26 cases, respectively]. RESULTS: A complete response at 6 months was evidenced in 101/152 (66%) patients on TNF-α antagonists and 75/107 (70%) patients on tocilizumab. Age ≥30 years [odds ratio 2.09 (95% CI 1.09, 3.99)] was associated with complete response, whereas vascular signs [OR 0.26 (95% CI 0.1, 0.65)], baseline prednisone ≥20 mg/day [OR 0.51 (95% CI 0.28, 0.93)] were negatively associated with the complete response to TNF-α antagonists or tocilizumab. During a median follow-up of 36 months, 103 relapses were noted. Supra-aortic branches and thoracic aorta involvement [HR 2.44 (95% CI 1.06, 5.65) and 3.66 (1.18, 11.4), respectively] and systemic signs at baseline [HR 2.01 (95% CI 1.30, 3.11)] were significantly associated with relapse. The cumulative incidence of treatment discontinuation and relapse were similar in TNF-α antagonists and tocilizumab. Fifty-eight (20%) adverse effects occurred on biologic targeted therapies [37 (21%) on TNF-α antagonists and 21 (17%) on tocilizumab (P = 0.4), respectively]. CONCLUSION: This large multicentre study shows high efficacy of biologic targeted treatments in refractory TAK. Efficacy, relapse and drug retention rate were equivalent with TNF-α antagonists and tocilizumab.

Anti-Tumor Necrosis Factor α versus Tocilizumab in the Treatment of Refractory Uveitic Macular Edema: A Multicenter Study from the French Uveitis Network.

PURPOSE: To analyze the factors associated with response (control of ocular inflammation and corticosteroid-sparing effect) to biologics (anti-tumor necrosis factor [TNF]-α agents and tocilizumab) in patients with refractory uveitic macular edema (ME). DESIGN: Multicenter, retrospective, observational study. PARTICIPANTS: Adult patients with uveitic ME refractory to systemic corticosteroids, disease-modifying antirheumatic drugs, or both. METHODS: Patients received anti-TNF-α agents (infliximab 5 mg/kg at week 0, 2, 6, and every 4-6 weeks [n = 69] and adalimumab 40 mg/2 weeks [n = 80]) and tocilizumab (8 mg/kg every 4 weeks intravenously [n = 39] and 162 mg/week subcutaneously [n = 16]). MAIN OUTCOME MEASURES: Analysis of complete and partial response rates, relapse rate, low vision (visual acuity in at least 1 eye of ≥ 1 logarithm of the minimum angle of resolution), corticosteroid-sparing effect, and adverse events at 6 months. RESULTS: Two hundred four patients (median age, 40 years [interquartile range, 28-58 years]; 42.2% men) were included. Main causes of uveitis included Behçet's disease (17.2%), birdshot chorioretinopathy (11.3%), and sarcoidosis (7.4%). The overall response rate at 6 months was 46.2% (21.8% of complete response) with anti-TNF-α agents and 58.5% (35.8% of complete response) with tocilizumab. In multivariate analysis, treatment with tocilizumab (odds ratio, 2.10; 95% confidence interval [CI], 1.06-4.06; P = 0.03) was associated independently with complete response of uveitic ME compared with anti-TNF-α agents. Anti-TNF-α agents and tocilizumab did not differ significantly in terms of relapse rate (hazard ratio, 1.00; 95% CI, 0.31-3.18; P = 0.99) or occurrence of low vision (odds ratio, 1.02; 95% CI, 0.51-2.07; P = 0.95) or corticosteroid-sparing effect (P = 0.29). Adverse events were reported in 20.6% of patients, including serious adverse events reported in 10.8% of patients. CONCLUSIONS: Tocilizumab seems to improve complete response of uveitic ME compared with anti-TNF-α agents.

Early diffusion-weighted MRI at 3 Tesla detects ischemic changes of the optic nerve in anterior ischemic optic neuropathy.

OBJECTIVES: To assess the impact of timing from visual symptoms' onset to diffusion-weighted (DW) 3 T MRI completion to detect ischemic changes of the optic disc and optic nerve in AION patients. METHODS: This IRB-approved retrospective single-center study included 3 T MRI data from 126 patients with AION and 111 controls with optic neuritis treated between January 2015 and May 2020. Two radiologists blinded to all data individually analyzed imaging. A senior neuroradiologist resolved any discrepancies by consensus. The primary judgment criterion was the restricted diffusion of the optic disc and/or the optic nerve assessed subjectively on the ADC maps. ADC values were also measured. Spearman rank correlations were used to examine the relationships between timing from visual symptoms' onset to MRI completion and both the restricted diffusion and the ADC values. RESULTS: One hundred twenty-six patients (47/126 [37.3%] women and 79/126 [62.7%] men, mean age 69.1 ± 13.7 years) with AION were included. Restricted diffusion of the optic disc in AION eyes was more frequent in the early MRI group than in the late MRI group: 35/49 (71.4%) eyes versus 3/83 (3.6%) eyes, p < 0.001. ADC values of the pathological optic discs and optic nerves were lower in the early MRI group than in the late MRI group: 0.61 [0.52-0.94] × 10-3 mm2/s versus 1.28 [1.01-1.44] × 10-3 mm2/s, p < 0.001, and 0.74 [0.61-0.88] × 10-3 mm2/s versus 0.89 [0.72-1.10] × 10-3 mm2/s, p < 0.001, respectively. CONCLUSIONS: DWI MRI showed good diagnostic performance to detect AION when performed early after the onset of visual symptoms. KEY POINTS: • Restricted diffusion of the optic disc in eyes affected by AION was significantly more likely to be observed in patients who had undergone MRI within 5 days after onset of visual symptoms. • ADC values of the pathological optic discs and optic nerves were significantly lower in patients who had undergone MRI within 5 days after onset of visual symptoms of AION: 0.61 × 10-3 mm2/s versus 1.28 × 10-3 mm2/s, p < 0.001, and 0.74 × 10-3 mm2/s versus 0.89 × 10-3 mm2/s, p < 0.001, respectively. • The optimal threshold for timing from visual symptoms' onset to MRI completion to detect restricted diffusion of the optic disc and/or optic nerve was 5 days, with an AUC of 0.88 (CI95%: 0.82-0.94).

PARACENTRAL ACUTE MIDDLE MACULOPATHY IN GIANT CELL ARTERITIS.

PURPOSE: To report the occurrence of paracentral acute middle maculopathy (PAMM) in giant cell arteritis (GCA), describe its features and outcomes, and identify risk factors associated with PAMM in patients with GCA. METHODS: Review of medical records of patients with GCA who were examined in the Rothschild Foundation Hospital. Patients were divided into three groups: GCA with PAMM (Group 1), GCA with ophthalmic involvement but without PAMM (Group 2), and GCA without ophthalmic involvement (Group 3). We analyzed the data for age, sex, medical history, laboratory testing, visual acuity, and posterior segment vascular involvement. RESULTS: Among the 96 patients who met the inclusion criteria, 52 had ophthalmic involvement, and 16 patients were included in Group 1 (GCA with PAMM). In this subgroup, the mean age was 81.6 years and was found to be older than other groups. The visual prognosis was similar between Groups 1 and 2. Of the 20 eyes with PAMM, 35% were also associated with homolateral anterior ischemic optic neuropathy. No statistical difference was found in initial symptoms, signs, and laboratory testing. CONCLUSION: Paracentral acute middle maculopathy is frequently observed lesions in ocular GCA. Patients can present with isolated findings of PAMM as the only indication of GCA. Optical coherence tomography of the macula should be routinely performed in patients with suspected GCA, specifically if they complain of visual changes, to look for signs of ischemia in the middle layers of the retina. Isolated PAMM should raise suspicion for GCA in patients at risk.

Incidence of giant cell arteritis in six districts of Paris, France (2015-2017).

This prospective population-based study estimated the incidence of giant cell arteritis (GCA) in northeastern Paris. GCA cases diagnosed between 2015 and 2017 were obtained from local hospital and community-based physicians and the national health insurance system database. Criteria for inclusion were living in the study area at that time and fulfilling the 1990 American College of Rheumatology classification criteria and/or its expanded version. Cranial and large-vessel GCA cases were defined by the presence or absence of cranial signs and/or symptoms, respectively. Annual incidence was calculated by dividing the number of incident cases by the size of the study population ≥ 50 years old. Completeness of case ascertainment was assessed by a three-source capture-recapture analysis. Among the 62 included cases, 42 (68%) were women, mean (± SD) age 77.3 ± 9.1 years. The annual incidence of GCA in northeastern Paris and completeness of case ascertainment were estimated at 7.6 (95% CI 5.9-9.8) per 100,000 inhabitants ≥ 50 years old and 66% (95% CI 52-92%), respectively. Incidence increased with age, peaked at age 80-89 years, and was almost twice as high in women versus men. Large-vessel GCA cases, mean (± SD) age 68.6 ± 11.5 years, accounted for 8% of all GCA cases. In this study, GCA epidemiology was mainly driven by cases with cranial GCA signs or symptoms and incidence results were consistent with recent European and past French studies.

Use of Retinal Angiography and MRI in the Diagnosis of Giant Cell Arteritis With Early Ophthalmic Manifestations.

BACKGROUND: Giant cell arteritis (GCA) is a vasculitis often revealed by visual signs. Diagnosis is challenging and urgent. Retinal angiography (RA) and MRI allow effective diagnosis. We compared those and proposed an imaging-based approach to diagnose GCA in ophthalmological practice. METHODS: We conducted a retrospective study based on the data collected from patients suspected to have GCA on ophthalmological findings. Fluorescein (FA) and indocyanine green (ICG) RAs and MRI were performed and compared with final diagnosis. RESULTS: Among the 41 patients included, 25 were diagnosed with GCA. Sensitivities and specificities of FA and ICG were not different. MRI showed a higher sensitivity and specificity. The approach consisting in performing RA followed by MRI provided a better accuracy. CONCLUSION: Our study shows that RA can be supplemented by MRI in a specialized center to provide the most accurate diagnosis in GCA revealed by visual signs.

TNF-α inhibitors used as steroid-sparing maintenance monotherapy in parenchymal CNS sarcoidosis.

OBJECTIVE: To assess the efficacy of tumour necrosis factor-α (TNF-α) inhibitors used as steroid-sparing monotherapy in central nervous system (CNS) parenchymal sarcoidosis. METHODS: The French Multiple Sclerosis and Neuroinflammation Centers retrospectively identified patients with definite or probable CNS sarcoidosis treated with TNF-α inhibitors as steroid-sparing monotherapy. Only patients with CNS parenchymal involvement demonstrated by MRI and imaging follow-up were included. The primary outcome was the minimum dose of steroids reached that was not associated with clinical or imaging worsening during a minimum of 3 months after dosing change. RESULTS: Of the identified 38 patients with CNS sarcoidosis treated with TNF-α inhibitors, 23 fulfilled all criteria (13 females). Treatments were infliximab (n=22) or adalimumab (n=1) for a median (IQR) of 24 (17-40) months. At treatment initiation, the mean (SD) age was 41.5 (10.5) years and median (IQR) disease duration 22 (14-49.5) months. Overall, 60% of patients received other immunosuppressive agents before a TNF-α inhibitor. The mean (SD) minimum dose of steroids was 31.5 (33) mg before TNF-α inhibitor initiation and 6.5 (5.5) mg after (p=0.001). In all, 65% of patients achieved steroids dosing <6 mg/day; 61% showed clinical improvement, 30% stability and 9% disease worsening. Imaging revealed improvement in 74% of patients and stability in 26%. CONCLUSION: TNF-α inhibitors can greatly reduce steroids dosing in patients with CNS parenchymal sarcoidosis, even refractory. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that TNF-α inhibitor used as steroid-sparing monotherapy is effective for patients with CNS parenchymal sarcoidosis.

White blood count, D-dimers, and ferritin levels as predictive factors of pulmonary embolism suspected upon admission in noncritically ill COVID-19 patients: The French multicenter CLOTVID retrospective study.

BACKGROUND: A high prevalence of pulmonary embolism (PE) has been described during COVID-19. Our aim was to identify predictive factors of PE in non-ICU hospitalized COVID-19 patients. METHODS: Data and outcomes were collected upon admission during a French multicenter retrospective study, including patients hospitalized for COVID-19, with a CT pulmonary angiography (CTPA) performed in the emergency department for suspected PE. Predictive factors significantly associated with PE were identified through a multivariate regression model. RESULTS: A total of 88 patients (median [IQR] age of 68 years [60-78]) were analyzed. Based on CTPA, 47 (53.4%) patients were diagnosed with PE, and 41 were not. D-dimer ≥3000 ng/mL (OR 8.2 [95% CI] 1.3-74.2, sensitivity (Se) 0.84, specificity (Sp) 0.78, P = .03), white blood count (WBC) ≥12.0 G/L (29.5 [2.3-1221.2], Se 0.47, Sp 0.92, P = .02), and ferritin ≥480 µg/L (17.0 [1.7-553.3], Se 0.96, Sp 0.44, P = .03) were independently associated with the PE diagnosis. The presence of the double criterion D-dimer ≥3000 ng/mL and WBC ≥12.0 G/L was greatly associated with PE (OR 21.4 [4.0-397.9], P = .004). CONCLUSION: The white blood count, the D-dimer and ferritin levels could be used as an indication for CTPA to confirm PE on admission in non-ICU COVID-19 patients.

High-resolution MRI demonstrates signal abnormalities of the 3rd cranial nerve in giant cell arteritis patients with 3rd cranial nerve impairment.

OBJECTIVE: To determine the sensitivity and specificity of high-resolution (HR) MRI for detecting signal abnormalities of cranial nerves (CN) in giant cell arteritis (GCA) patients presenting with diplopia. METHODS: This IRB-approved retrospective single-center study included GCA patients who underwent 3-T HR MRI from December 2014 to January 2020. Two radiologists, blinded to all data, individually assessed for the presence of enhancement of the 3rd, 4th, and/or 6th CN on post-contrast HR imaging and high signal intensity on HR T2-WI, for signal abnormalities of extraocular muscles and the brainstem, and for inflammatory changes of the ophthalmic and extracranial arteries. A Fisher's exact test was used to compare patients with or without diplopia. RESULTS: In total, 64 patients (42/64 (66%) women and 22/64 (34%) men, mean age 76.3 ± 8 years) were included. Of the 64 patients, 14 (21.9%) presented with diplopia. Third CN enhancement was detected in 7/8 (87.5%) patients with 3rd CN impairment, as compared to no patients with 4th or 6th CN impairment or to patients without diplopia (p < 0.001). Third CN abnormal high signal intensity on HR T2-WI was detected in 4/5 patients (80%) with 3rd CN impairment versus none of other patients (p < 0.001). Sensitivity, specificity, positive predictive value, and negative predictive value for detecting 3rd CN signal abnormalities were of 0.88, 1, 1, and 0.99 and 0.8, 1, 1, and 0.98 for post-contrast HR imaging and HR T2-WI, respectively. CONCLUSIONS: HR MRI had excellent diagnostic sensitivity and specificity when detecting signal abnormalities of the 3rd CN in GCA patients presenting with 3rd CN impairment. KEY POINTS: • Third cranial nerve enhancement was detected in all patients with 3rd cranial nerve impairment except for one with transient diplopia. • The "check mark sign" might be useful to identify 3rd cranial nerve signal abnormalities in the orbital apex. • No signal abnormalities of the 4th or 6th cranial nerves could be detected on high-resolution MRI.

Positive Effects of Local Botulinum Toxin Injection and Colchicine for Complicated Chronic Recurrent Parotitis: A Case Report.

Chronic recurrent parotitis (CRP) is a rare affliction of unknown cause characterized by recurrent episodes of unilateral or bilateral nonobstructive and nonsuppurative inflammation of the parotid glands. Management of CRP is not standardized, and attempts at treatment often fail. We report a case of a 29-year-old female patient with CRP for 13 years, with recurrent acute episodes, complicated with a collection and cutaneous fistula, refractory to repeated courses of corticosteroids and antibiotics. Injections of botulinum toxin in the parotid gland and maintenance treatment with oral colchicine lead to a rapid and sustained improvement. Local botulinum toxin injections associated with colchicine might represent a safe and noninvasive treatment of CRP. The possible beneficial effect of colchicine could be an argument for auto-inflammatory participation in the pathogenesis of CRP.

Myelin oligodendrocyte glycoprotein antibody-associated diffuse orbital inflammation.

An 87-year-old man presented with a 2-day history of painful bilateral visual loss. On examination, exophthalmos, lid edema, chemosis, and optic disc edema, on the left side only, were found. Visual acuity was 4/10 OD and no light perception OS. Magnetic resonance imaging (MRI) revealed bilateral optic neuritis and a diffuse and severe infiltration of the intra- and extraconal fat on the left. Laboratory testing was negative except for serum myelin oligodendrocyte glycoprotein (MOG) antibodies. This presentation adds a new variant to the MOG-associated disease spectrum. Testing for MOG antibodies should be considered in patients presenting with diffuse orbital inflammation and optic neuritis.

Increased diagnostic accuracy of giant cell arteritis using three-dimensional fat-saturated contrast-enhanced vessel-wall magnetic resonance imaging at 3 T.

OBJECTIVES: To compare the diagnostic accuracy of 3D versus 2D contrast-enhanced vessel-wall (CE-VW) MRI of extracranial and intracranial arteries in the diagnosis of GCA. METHODS: This prospective two-center study was approved by a national research ethics board and enrolled participants from December 2014 to October 2017. A protocol including both a 2D and a 3D CE-VW MRI at 3 T was performed in all patients. Two neuroradiologists, blinded to clinical data, individually analyzed separately and in random order 2D and 3D sequences in the axial plane only or with reformatting. The primary judgment criterion was the presence of GCA-related inflammatory changes of extracranial arteries. Secondary judgment criteria included inflammatory changes of intracranial arteries and the presence of artifacts. A McNemar's test was used to compare 2D to 3D CE-VW MRIs. RESULTS: Seventy-nine participants were included in the study (42 men and 37 women, mean age 75 (± 9.5 years)). Fifty-one had a final diagnosis of GCA. Reformatted 3D CE-VW was significantly more sensitive than axial-only 3D CE-VW or 2D CE-VW when showing inflammatory change of extracranial arteries: 41/51(80%) versus 37/51 (73%) (p = 0.046) and 35/50 (70%) (p = 0.03). Reformatted 3D CE-VW was significantly more specific than 2D CE-VW: 27/27 (100%) versus 22/26 (85%) (p = 0.04). 3D CE-VW showed higher sensitivity than 2D CE-VW when detecting inflammatory changes of intracranial arteries: 10/51(20%) versus 4/50(8%), p = 0.01. Interobserver agreement was excellent for both 2D and 3D CE-VW MRI: κ = 0.84 and 0.82 respectively. CONCLUSIONS: 3D CE-VW MRI supported more accurate diagnoses of GCA than 2D CE-VW. KEY POINTS: • 3D contrast-enhanced vessel-wall magnetic resonance imaging is a high accuracy, non-invasive diagnostic tool used to diagnose giant cell arteritis. • 3D contrast-enhanced vessel-wall imaging is feasible for clinicians to complete within a relatively short time, allowing immediate assessment of extra and intracranial arteries. • 3D contrast-enhanced vessel-wall magnetic resonance imaging might be considered a diagnostic tool when intracranial manifestation of GCA is suspected.

High prevalence of myeloid neoplasms in adults with non-Langerhans cell histiocytosis.

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis that most commonly affects adults and is driven by a high frequency of mutations in BRAF, MAP2K1, and kinases promoting MAPK signaling. Because of the relative rarity of ECD, key clinical features of the disease may not be well defined. Across a multi-institutional cohort of 189 patients with ECD and ECD overlapping with Langerhans cell histiocytosis (so-called mixed histiocytosis [MH]), we identified an unexpected and heretofore undescribed frequent occurrence of myeloid neoplasms among patients with ECD and MH. Some 10.1% (19/189) of patients with ECD have an overlapping myeloid neoplasm, most commonly occurring as a myeloproliferative neoplasm (MPN), myelodysplastic syndrome (MDS), or mixed MDS/MPN overlap syndrome (including chronic myelomonocytic leukemia). Consistent with this, molecular analysis frequently detected hallmark driver mutations of myeloid neoplasms (such as JAK2V617F and CALR mutations) coexisting with those characteristic of histiocytosis (such as BRAFV600E and MAP2K1 mutations). Histiocytosis patients diagnosed with a concomitant myeloid malignancy were significantly older at diagnosis and more commonly presented with MH than those without a myeloid malignancy. In some cases, the presence of distinct kinase mutations in the histiocytosis and myeloid neoplasm resulted in discordant and adverse responses to kinase-directed targeted therapies. These data highlight the clinical importance of evaluating adults with histiocytosis for a concomitant myeloid neoplasm.

Extra-haematological manifestations related to human parvovirus B19 infection: retrospective study in 25 adults.

BACKGROUND: To describe extra-haematological manifestations associated with human parvovirus B19 (HPV-B19) infection. METHODS: We conducted a nationwide multicentre study to retrospectively describe the characteristics and outcome of extra-haematological manifestations in French adults. RESULTS: Data from 25 patients followed from 2001 to 2016 were analysed. Median age was 37.9 years (range: 22.7-83.4), with a female predominance (sex ratio: 4/1). Only 3 patients had an underlying predisposing condition (hemoglobinopathy or pregnancy). The most common manifestations were joint (80%) and skin (60%) involvement. Four patients (16%) had renal involvement (endocapillary proliferative or membranoproliferative glomerulonephritis, focal segmental glomerulosclerosis). Three patients (12%) had peripheral nervous system involvement (mononeuritis, mononeuritis multiplex, Guillain-Barré syndrome) and 2 (8%) presented muscle involvement. Other manifestations included hemophagocytic lymphohistiocytosis (n = 1), myopericarditis and pleural effusion (n = 1), and lymphadenopathy and splenomegaly mimicking lymphoma with spleen infarcts (n = 1). Immunological abnormalities were frequent (56.5%). At 6 months, all patients were alive, and 54.2% were in complete remission. In 2 patients, joint involvement evolved into rheumatoid arthritis. Six patients (24%) received intravenous immunoglobulin (IVIg), with a good response in the 3 patients with peripheral nervous system involvement. CONCLUSIONS: HPV-B19 infection should be considered in a wide range of clinical manifestations. Although the prognosis is good, IVIg therapy should be discussed in patients with peripheral nerve involvement. However, its efficacy should be further investigated in prospective studies.

Impact of eculizumab treatment on paroxysmal nocturnal hemoglobinuria: a treatment versus no-treatment study.

Intravascular hemolysis in Paroxysmal nocturnal hemoglobinuria (PNH) can effectively be controlled with eculizumab, a humanized monoclonal antibody that binds complement protein C5. We report here a retrospective comparison study between 123 patients treated with eculizumab in the recent period (>2005) and 191 historical controls (from the French registry). Overall survival (OS) at 6 years was 92% (95%CI, 87 to 98) in the eculizumab cohort versus 80% (95%CI 70 to 91) in historical controls diagnosed after 1985 (HR 0.38 [0.15 to 0.94], P = 0.037). There were significantly fewer thrombotic events (TEs) in the group of patients treated with eculizumab (4% [1-10]) as compared to the historical cohort (27% [20-34]). However, we found that TEs may still occur after the initiation of eculizumab treatment and that previous TEs still have a negative impact on survival. Evolutions to myelodysplastic syndrome or acute leukemia were similar in both cohorts. There was less evolution to aplastic anemia in the treatment group. In multivariate analysis, absence of a previous TE and treatment with eculizumab were associated with a better OS. Treatment with eculizumab improves overall survival in classic PNH patients without increasing the risk of clonal evolution.