Immunotherapies in neuromyelitis optica spectrum disorder: efficacy and predictors of response

OBJECTIVE: To analyse predictors for relapses and number of attacks under different immunotherapies in patients with neuromyelitis optica spectrum disorder (NMOSD). DESIGN: This is a retrospective cohort study conducted in neurology departments at 21 regional and university hospitals in Germany. Eligible participants were patients with aquaporin-4-antibody-positive or aquaporin-4-antibody-negative NMOSD. Main outcome measures were HRs from Cox proportional hazard regression models adjusted for centre effects, important prognostic factors and repeated treatment episodes. RESULTS: 265 treatment episodes with a mean duration of 442 days (total of 321 treatment years) in 144 patients (mean age at first attack: 40.9 years, 82.6% female, 86.1% aquaporin-4-antibody-positive) were analysed. 191 attacks occurred during any of the treatments (annual relapse rate=0.60). The most common treatments were rituximab (n=77, 111 patient-years), azathioprine (n=52, 68 patient-years), interferon-beta (n=32, 61 patient-years), mitoxantrone (n=34, 32.1 patient-years) and glatiramer acetate (n=17, 10 patient-years). Azathioprine (HR=0.4, 95% CI 0.3 to 0.7, p=0.001) and rituximab (HR=0.6, 95% CI 0.4 to 1.0, p=0.034) reduced the attack risk compared with interferon-beta, whereas mitoxantrone and glatiramer acetate did not. Patients who were aquaporin-4-antibody-positive had a higher risk of attacks (HR=2.5, 95% CI 1.3 to 5.1, p=0.009). Every decade of age was associated with a lower risk for attacks (HR=0.8, 95% CI 0.7 to 1.0, p=0.039). A previous attack under the same treatment tended to be predictive for further attacks (HR=1.5, 95% CI 1.0 to 2.4, p=0.065). CONCLUSIONS: Age, antibody status and possibly previous attacks predict further attacks in patients treated for NMOSD. Azathioprine and rituximab are superior to interferon-beta

Pain, depression and quality of life in adults with MOG-antibody associated disease

BACKGROUND AND PURPOSE: Myelin oligodendrocyte glycoprotein-antibody (MOG-ab)-associated disease (MOGAD) is an inflammatory autoimmune condition of the CNS. However, data on pain and depression have remained scarce. The aim of this study was to assess features of chronic pain and depression as well as their impact on health-related quality of life (hr-QoL) in MOGAD. METHODS: Patients with MOGAD were identified in the Neuromyelitis Optica Study Group (NEMOS) registry. Data were acquired by a questionnaire, including clinical, demographic, pain (PainDetect, Brief Pain Inventory - short form, McGill Pain Questionnaire - short form), depression (Beck Depression Inventory-II), and hr-QoL (Short Form-36 Health Survey) items. RESULTS: Twenty-two of 43 patients suffered from MOGAD-related pain (11 nociceptive, 8 definite neuropathic, 3 possible neuropathic) and 18 from depression. Patients with neuropathic pain had highest pain intensity and most profound ADL impairment. Fifteen patients reported spasticity-associated pain, including four with short-lasting painful tonic spasms. Later disease onset, profound physical impairment and depression were associated with chronic pain. Physical QoL was more affected in pain-sufferers (p<0.001) than in pain-free patients, being most severely reduced by neuropathic pain (p=0.016). Pain severity, visual impairment, and gait impairment independently predicted lower physical QoL. Depression was the only factor reducing mental QoL. Twelve patients received pain medication, still suffering from moderate pain (pain severity 4.6±2.3). Only four out of ten patients with moderate to severe depression took antidepressants. CONCLUSIONS: Being highly prevalent, pain and depression strongly affect QoL and ADL in MOGAD. Both conditions remain insufficiently controlled in real-life clinical practice

Interleukin-6 receptor blockade in treatment-refractory MOG-IgG-associated disease and neuromyelitis optica spectrum disorders

BACKGROUND AND OBJECTIVES: To evaluate the long-term safety and efficacy of tocilizumab (TCZ), a humanized anti-interleukin-6 receptor antibody in myelin oligodendrocyte glycoprotein-IgG-associated disease (MOGAD) and neuromyelitis optica spectrum disorders (NMOSD). METHODS: Annualized relapse rate (ARR), Expanded Disability Status Scale score, MRI, autoantibody titers, pain, and adverse events were retrospectively evaluated in 57 patients with MOGAD (n = 14), aquaporin-4 (AQP4)-IgG seropositive (n = 36), and seronegative NMOSD (n = 7; 12%), switched to TCZ from previous immunotherapies, particularly rituximab. RESULTS: Patients received TCZ for 23.8 months (median; interquartile range 13.0-51.1 months), with an IV dose of 8.0 mg/kg (median; range 6-12 mg/kg) every 31.6 days (mean; range 26-44 days). For MOGAD, the median ARR decreased from 1.75 (range 0.5-5) to 0 (range 0-0.9; p = 0.0011) under TCZ. A similar effect was seen for AQP4-IgG+ (ARR reduction from 1.5 [range 0-5] to 0 [range 0-4.2]; p < 0.001) and for seronegative NMOSD (from 3.0 [range 1.0-3.0] to 0.2 [range 0-2.0]; p = 0.031). During TCZ, 60% of all patients were relapse free (79% for MOGAD, 56% for AQP4-IgG+, and 43% for seronegative NMOSD). Disability follow-up indicated stabilization. MRI inflammatory activity decreased in MOGAD (p = 0.04; for the brain) and in AQP4-IgG+ NMOSD (p < 0.001; for the spinal cord). Chronic pain was unchanged. Regarding only patients treated with TCZ for at least 12 months (n = 44), ARR reductions were confirmed, including the subgroups of MOGAD (n = 11) and AQP4-IgG+ patients (n = 28). Similarly, in the group of patients treated with TCZ for at least 12 months, 59% of them were relapse free, with 73% for MOGAD, 57% for AQP4-IgG+, and 40% for patients with seronegative NMOSD. No severe or unexpected safety signals were observed. Add-on therapy showed no advantage compared with TCZ monotherapy. DISCUSSION: This study provides Class III evidence that long-term TCZ therapy is safe and reduces relapse probability in MOGAD and AQP4-IgG+ NMOSD

Preis- und Mengenvariabilitaet bei Stagflation

SIGLEBibliothek Weltwirtschaft Kiel C126,831 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

Relative Preise, gesamtwirtschaftliche Aktivitaet und Strukturwandel

SIGLEBibliothek Weltwirtschaft Kiel C 148111 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

Zu den Leitlinien fuer eine Politik der positiven Strukturanpassung

SIGLEBibliothek Weltwirtschaft Kiel C125,656 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

Der Innovationsprozess, die internationale Wettbewerbsfaehigkeit und die Rolle des Staates

Bibliothek Weltwirtschaft Kiel C 148112 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Strukturerhaltung als Behinderung der internationalen Wettbewerbsfaehigkeit der deutschen Wirtschaft

SIGLEBibliothek Weltwirtschaft Kiel C131,105 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

Zur internationalen Wettbewerbsfaehigkeit der deutschen Wirtschaft

SIGLEBibliothek Weltwirtschaft Kiel C 134494 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman