Sarilumab reduces disease activity in rheumatoid arthritis patients with inadequate response to janus kinase inhibitors or tocilizumab in regular care in Germany.

OBJECTIVES: The aim was to evaluate the safety and effectiveness of sarilumab in RA patients after inadequate response (IR) to janus kinase inhibitors (JAKi) and tocilizumab. METHODS: The prospective, observational, 24-month single-arm PROSARA study (SARILL08661) is currently running in Germany at 96 sites. RA patients were prospectively selected at the physician's discretion according to label. This interim analysis included 536 patients over a treatment course of ≤6 months. Patients were stratified in four groups according to pretreatment before the start of sarilumab therapy: last prior treatment JAKi (JAKi-IR); last prior treatment tocilizumab (tocilizumab-IR); any other biological DMARD (bDMARD) in treatment history (bDMARD TH); and patients who had not received any bDMARDs or targeted synthetic (ts) DMARDs (b/tsDMARD naive) before. RESULTS: For this preplanned interim analysis, 536 patients were included in the baseline population, of whom 502 patients had at least one corresponding post-baseline effectiveness assessment documented (main analysis population). In all analysed cohorts, safety was consistent with the anticipated profile of sarilumab, without new safety signals. Six months of sarilumab treatment attenuated disease activity in JAKi-IR, tocilizumab-IR, bDMARD TH and b/tsDMARD-naive patients to a very similar extent. Physical function did not change substantially over the course of treatment. Rates of premature study discontinuation were comparable between cohorts. CONCLUSION: Sarilumab treatment was effective in patients with IR to JAKi and tocilizumab, with an expectable safety profile and drug retention over 6 months. Confirmation of these promising results should encourage further studies on this treatment sequence, which is of high practical relevance. STUDY REGISTRATION: Paul-Ehrlich-Institut-Federal Institute for Vaccine and Biomedics, SARILL08661.

[Anti B-cell-antibody treatment for maintenance of remission in granulomatosis with polyangiitis and microscopic polyangiitis]. / Anti-B-Zell-Antikörpertherapie zur Remissionserhaltung bei Granulomatose mit Polyangiitis und mikroskopischer Polyangiitis.

Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are the most frequent primary necrotizing small vessel vasculitides. In these formerly fatal diseases remission can be induced by stage- and activity-adapted immunosuppressive regimens in the majority of patients. This does not lead to drug-free long-term remission or even cure. Consequently, maintenance of remission medication is needed. Recent randomized controlled trials demonstrated that maintenance treatment with the anti-B-cell antibody Rituximab, administered 6-monthly as opposed to azathioprine leads to a significantly lower relapse rate but a similar profile of adverse events. These data enabled the extension of the approval of Rituximab for maintenance of remission treatment of GPA and MPA in Germany in 2018. Guidelines and expert recommendations concerning measures of infection prevention and vaccination of immunosuppressed patients as well as the management of hypogammaglobulinemia and cytopenia on Rituximab are presented in this review.

[Actual Treatment Options for Giant Cell Arteritis]. / Aktuelle Optionen zur Behandlung der Riesenzellarteriitis.

To prevent serious complications such as permanent loss of vision and structural vascular damage, treatment must be initiated quickly in patients with giant-cell arteritis (GCA). So far, usually long-term corticosteroids in cumulative high dosages have been the standard therapy option. However, steroids are often insufficient to achieve adequate disease control and are associated with serious adverse events. Therefore, steroid-sparing therapy options are the focus of interest.

Intravenous immunoglobulin therapy in vasculitis: speculation or evidence?

Initially, intravenous immunoglobulins (IVIgs) were used as replacement therapy in primary and secondary antibody-deficiency syndromes. The clinical use of IVIg has been extended during the past decade to a wide variety of clinical conditions, such as infectious processes, neuroimmunological diseases, and different systemic autoimmune diseases. The mode of action of IVIg is complex, involving modulation of the Fc receptors, interference with the complement and cytokine network, and effects on the activation and differentiation of T and B-cells. Kawasaki disease (KD) was one of the first diseases within the group of primary vasculitides in which IVIg were used. Today, there is a clear evidence of benefit for IVIg in the treatment of coronary artery abnormalities related to KD. Subsequently, various reports have suggested a beneficial effect in other vasculitides; however, there are few data from controlled studies. For antineutrophil cytoplasmic antibody-associated vasculitis (AAV) one placebo-controlled and several open-label studies have shown a beneficial effect on the disease activity in patients with Wegener's granulomatosis or microscopic polyangiitis refractory to standard therapy with prednisone and cyclophosphamide. For other vasculitides, such as polyarteritis nodosa or Henoch-Schonlein purpura, only case reports have described an inhibition of a disease progression by IVIg so far. However, the effect was partly only temporary. In conclusion, KD and AAV are the only vasculitides with a definite beneficial use of IVIg. For other vasculitides, the efficacy of IVIg has not been proven properly but may be useful in single cases.