Tocilizumab (TCZ) and tumour necrosis factor inhibitors (TNFi) are recommended for the treatment of rheumatoid arthritis (RA) in patients with inadequate response (IR) to prior disease-modifying antirheumatic drugs (DMARDs). This retrospective analysis assessed the efficacy of TCZ and TNFi, alone or in combination with DMARDs, in 1603 patients with IR to previous treatment with either DMARDs (DMARD-IR) and/or TNFi (TNFi-IR), initiating treatment with TCZ or a TNFi, managed in routine clinical practice. Patients were grouped according to treatment history and treatment initiated: DMARD-IR patients initiating treatment with TCZ + DMARD (DMARD-IR TCZ) or TNFi + DMARD (DMARD-IR TNFi), DMARD-IR and/or TNFi-IR patients initiating treatment with TCZ monotherapy (TCZ mono) or TNFi monotherapy (TNFi mono), and TNFi-IR patients initiating treatment with TCZ + DMARD (TNFi-IR TCZ) or TNFi + DMARD (TNFi-IR TNFi). Patients initiating treatment with TCZ generally had more severe disease and longer disease duration compared with the corresponding TNFi group. Significantly more patients achieved remission (DAS28 ESR <2.6) in the TCZ groups compared with corresponding TNFi groups (DMARD-IR, TCZ 44.0 % vs. TNFi 29.6 %; monotherapy, TCZ 37.2 % vs. TNFi 30.2 %; TNF-IR, TCZ 41.3 % vs. TNFi 19.2 %; p < 0.001 for all comparisons). More patients achieved moderate–good responses (EULAR criteria) in the TCZ treatment groups (79–85 %) compared with TNFi treatment groups (65–81 %). Patient-reported outcomes showed greater improvements in TCZ compared with TNFi groups. In patients with inadequate response to DMARDs and/or TNFi treated in routine clinical practice, TCZ in combination with DMARDs or as monotherapy resulted in significantly more patients achieving remission and more marked improvements in patient-reported outcomes compared with TNF inhibitors.

This paper aims to raise awareness of the different disease courses, comorbidities, and therapy situations in patients with giant cell arteritis (GCA), which require a differentiated approach and often a deviation from current treatment guidelines. With the approval of tocilizumab (TOC), which specifically binds to both soluble and membrane-bound IL-6 receptor and inhibits IL-6 receptor-mediated signaling, the spectrum of available effective treatment options has been significantly broadened. TOC yields an extensive range of possible applications that go beyond a glucocorticoid-saving effect. In this context, the treatment of GCA is dependent on the disease course as well as the associated comorbidities. The different stages of GCA in association to co-morbidities require a detailed treatment strategy.

The individual risk of infection and requirements for medical treatment after high-dose chemotherapy have been unpredictable. In this prospective, multicenter, open-label study we investigated the potential of granulocyte colony-stimulating factor (G-CSF) responsiveness as a predictor. A total of 168 patients with multiple myeloma or lymphoma received a single dose of subcutaneous G-CSF (lenograstim, 263 g) after high-dose chemotherapy. Highly variable leukocyte peaks were measured and grouped as low (quartile 1; leukocytes 100-10 100/L), medium (quartile 2; leukocytes > 10 100-18 300/L), and high (quartiles 3/4; leukocytes > 18 300-44 800/L). G-CSF responsiveness (low vs medium vs high) was inversely correlated with febrile neutropenia (77% vs 60% vs 48%; P ‫؍‬ .0037); the rate of infection, including fever of unknown origin (91% vs 67% vs 54%; P < .0001); days with intravenous antibiotics (9 vs 6 vs 5; P < .0001); and antifungal therapy (P ‫؍‬ .042). In multivariate analysis, G-CSF responsiveness remained the only factor significantly associated with infection (P ‫؍‬ .016). In addition, G-CSF responsiveness was inversely correlated with grade 3/4 oral mucositis (67% vs 33% vs 23%; P < .0001). G-CSF responsiveness appears as a signature of the myeloid marrow reserve predicting defense against neutropenic infection after intensive chemotherapy. This study is registered at http://www.clinicaltrials. gov as NCT01085058. (Blood. 2011;117(7): 2121-2128)

Background The ICHIBAN study collects clinical routine data to evaluate the efficacy and safety of tocilizumab (TCZ) in pat. with rheumatoid arthritis (RA) over a period of 2 years. Methods The start of this prospective, non-interventional study, being intended to include 4000 pat., was in Feb. 2010. Clinical data of RA pat., their therapies, therapeutic responses, pat. related outcomes and adverse events are collected “on the fly” using an online database with structured web forms. Results On 18th December 2011 as reference date, baseline data of 1036 pat. were available. In 343 pat. observation period was already at least 52 weeks or discontinuation or change of a treatment was documented. 75.4% of the 1036 pat. were female, the mean age was 56.0 years. Pat. suffered from RA since 10.1 years in mean and the baseline DAS28 was 5.4. 73.3% of the pat. had concomitant diseases. 74.4% were pretreated with TNF-alpha inhibitors, 23.9% exclusively with synthetic DMARDs. In week 52 (LOCF) 31.1% of the pat. (N=97/312) showed a remission of DAS28 (<2,6). A moderate or good EULAR response was seen in 32.3% or 42.2% of the pat., respectively. The mean number of tender joints decreased from 10.1 to 4.4, the mean number of swollen joints from 7.3 to 2.5. The mean ESR decreased from 35.4 to 13.7 mm/1h and the CRP from 3.3 to 0.8 mg/dl. Data on pat. reported outcomes (PRO) and functional status at week 52 are shown in Tab. 1. In 21.9% of the pat. (N=75/343) treatment was changed during the observational period of 52 weeks. The total TCZ exposition was 910.1 pat. years. 781 adverse events were reported (in 339 of the 1036 pat.; 85.8/100 pat. years). 147 of these events were infections (16.2/100 pat. years). 160 serious adverse events were reported (in 95 pat.; 17.6/100 pat. years), 110 of which included an at least improbable causal relationship with TCZ (12.1/100 pat. years). Table 1. Means of VAS scales (mm), FFbH and HAQ Week 0 (Baseline)Week 52 (LOCF)N Disease activity (100 = strongest possible activity)65.240.4249 Health state (100 = very bad)63.041.0248 Exhaustion/fatigue (100 = very strong)60.543.8246 Pain intensity (100 = intolerable pain)65.141.5247 Sleep disturbances (100 = very strong)49.739.8245 FFbH (%)58.664.4249 HAQ1.41.2221 Conclusions The results of this “real life study” represent a severely diseased RA population showing significant impairments. The first 343 patients having completed the first observation period of at least one year show clear improvements in all recorded RA parameters. These data confirm the results of previous real life studies with TCZ such as ROUTINE and TAMARA. The safety results correspond to the expectations. Disclosure of Interest C. Specker Grant/Research support from: Has received honoraria from Chugai for advising in study design and conduction and fees for talks, in summary less than €10.000/year, J. Kaufmann: None Declared, M. Vollmer: None Declared, H. Kellner: None Declared, M. Bohl-Bühler: None Declared, M. Aringer: None Declared, A. Alberding: None Declared, H. Schwenke:...

Background The ICHIBAN study collects routine clinical data to evaluate the effectiveness and safety of tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) in real world practice over a period of 2 years. Methods The start of this prospective, non-interventional study was in February 2010. The target recruitment is 4000 patients. Clinical data of RA patients, their therapies, therapeutic responses, patient reported outcomes and adverse events are collected in the process of normal practice using an online database with structured web forms. Results As of 1st December 2012, baseline data for 1895 patients were available. In 490 of these patients the observation period was at least 76 weeks under TCZ treatment, or treatment was interrupted or changed (analysis was performed according to LOCF method). The total TCZ exposure was 2299.8 patient years. 74.9% of the 1895 patients were female, the mean age was 56.3 years. Mean duration of RA was 10.0 years and baseline DAS28 was 5.1. 72.0% of the patients had concomitant diseases. 69.8% were pre-treated with TNF-alpha inhibitors, 28.0% exclusively with synthetic DMARDs. At baseline 40.1% of TCZ-treated patients did not receive any additional DMARD, while 46.0% were treated in combination with MTX. At W76, 34.0% of the patients (n=149/438) achieved DAS28 remission (<2.6). A moderate or good EULAR response was seen in 29.1% or 56.9% of the patients, respectively. The mean tender joint count (TJC) decreased from 9.6 to 3.5, the mean swollen joint count from 6.9 to 2.1. Mean ESR decreased from 35.5 to 10.6 mm/1h and CRP from 3.5 to 0.6 mg/dl. Data on patient reported outcomes (PRO) at week 76 are shown in Tab. 1. In 12.0% of the initially TCZ-treated patients (n=59/490) treatment was changed during the observational period. 1916 adverse events were reported (in 751/1895 patients; 83.3/100 patient years). 404 of these events were infections (17.6/100 patient years). 370 serious adverse events were reported (in 222 patients; 16.1/100 patient years), 219 of which (59.2%) were judged at least “unlikely” in relation to TCZ. Conclusions In daily practice TCZ treatment of patients with moderate to severe RA demonstrates good efficacy also in monotherapy and confirms the known safety profile. The first 490 patients having completed the observational period of at least one and a half years show clear improvements in all recorded RA parameters, as well as further improvements compared to the results after the first year of treatment. Disclosure of Interest C. Specker Grant/research support from: Has received honoraria from Chugai for advising in study design and conduction and fees for talks, in summary less than €10.000/year, J. Kaufmann: None Declared, H. Kellner: None Declared, M. Bohl-Bühler: None Declared, H. Schwenke: None Declared, M. Vollmer: None Declared, A. Kapelle: None Declared, S. Zinke: None Declared, M. Hofmann: None Declared, P. Hellmann: None Declared, G. Fliedner Grant/research support from: Has received honoraria from Chugai for advising in study de...