Interesting paper about IL-6 and inflammatory diseases

The Two-Faced Cytokine IL-6 in Host Defense and Diseases

5.2.1. Giant Cell Arteritis (GCA) and Takayasu Arteritis (TA)
The safety and effectiveness of TCZ for RA encouraged clinical trials of TCZ for various refractory inflammatory diseases. In 2017, the efficacy of TCZ was confirmed for diseases in a field other than inflammatory joint diseases. GCA is the most common large vessel vasculitis and cranial arteritis that affects individuals over the age of 50 and can lead to permanent visual loss. Most patients improve with glucocorticoids; however, some patients show disease flare after the reduction of treatment. A phase III GiACTA study involving 251 patients with GCA compared six months of treatment with prednisone taper plus TCZ (subcutaneous 162 mg) to prednisone taper alone. Fifty-six percent of patients receiving TCZ weekly and 53% receiving it every-other-week achieved sustained remission at 12 months compared to 14% in the six-month prednisone tapering alone group [111]. Treatment with TCZ plus prednisone led to a reduction in the cumulative dose of prednisone required to regulate GCA. In 2017, TCZ became the first GCA therapy to be approved by the USA, Japan and the EU. Another type of large vessel vasculitis is TA, often affecting women under the age of 40, in which arteries and their major branches narrow or cause aneurysms due to chronic inflammation of the vessel walls. Previously, glucocorticoids and immunosuppressive drugs, such as methotrexate or azathioprine, were usually used as treatment. In a phase III TAKT study, 19 patients with relapsed TA randomly received weekly TCZ (subcutaneous 162 mg) or placebo treatment. Although TCZ did not meet the defined primary endpoint for time to relapse TA, the hazard ratio for time to relapse was 0.41 (95.4% CI 0.15–1.10; p = 0.0596), suggesting a favorable effect of TCZ over the placebo [112]. A retrospective study of 46 patients with TA also showed the effectiveness of TCZ through significantly better event-free survival of patients who received TCZ compared with disease-modifying anti-rheumatic drugs (DMARDs) [113]. Japan approved TCZ for the treatment of TA in 2017. However, TA is known to frequently complicate inflammatory bowel disease [114]. Patients with inflammatory bowel disease should receive careful attention when receiving IL-6 inhibition therapy, because IL-6 has a protective effect of the intestinal epithelium.

5.3.2. Polymyalgia Rheumatica (PMR)
PMR is an inflammatory disease involving stiffness of the shoulders and pelvic girdles that occurs in people older than 50 years and is often associated with GCA. Usually, glucocorticoids are effective for treating PMR but some patients follow a chronic course and have glucocorticoid side effects. In a prospective study of 20 patients with active and recent onset PMR, all patients showed clinical improvement at 12 weeks after three TCZ (8 mg/kg) infusions at 4-week intervals [121]. A phase IIa trial involving newly diagnosed PMR patients also demonstrated the beneficial effects of TCZ on PMR [122]. All nine patients treated with intravenous TCZ (8 mg/kg) with a rapid tapering of glucocorticoids showed relapse-free remission without glucocorticoids after six months. Together, these reports suggest that TCZ is effective and reduces cumulative glucocorticoid doses in patients with PMR. Phase III clinical trial is being conducted (ClinicaTrials.gov NCT03263715).