Graves’ orbitopathy (GO) is the most common extrathyroidal manifestation of Graves’ disease (GD). Our aim was to assess the efficacy and safety of Tocilizumab (TCZ) in GO refractory to conventional therapy. This was an open-label multicenter study of glucocorticoid-resistant GO treated with TCZ. The main outcomes were the best-corrected visual acuity (BVCA), Clinical Activity Score (CAS) and intraocular pressure (IOP). These outcome variables were assessed at baseline, 1st, 3rd, 6th and 12th month after TCZ therapy onset. The severity of GO was assessed according to the European Group on Graves’ Orbitopathy (EUGOGO). We studied 48 (38 women and 10 men) patients (95 eyes); mean age ± standard deviation 51 ± 11.8 years. Before TCZ and besides oral glucocorticoids, they had received IV methylprednisolone (n = 43), or selenium (n = 11). GO disease was moderate (n =29) or severe (n = 19) and dysthyroid optic neuropathy (DON) (n = 7). TCZ was used in monotherapy (n = 45) or combined (n = 3) at a dose of 8 mg/kg IV every four weeks (n = 43) or 162 mg/s.c. every week (n = 5). TCZ yielded a significant improvement in all of the main outcomes at the 1st month that was maintained at one year. Comparing the baseline with data at 1 year all of the variables improved; BCVA (0.78 ± 0.25 vs. 0.9 ± 0.16; p = 0.0001), CAS (4.64 ± 1.5 vs. 1.05 ± 1.27; p = 0.0001) and intraocular pressure (IOP) (19.05 ± 4.1 vs. 16.73 ± 3.4 mmHg; p = 0.007). After a mean follow-up of 16.1 ± 2.1 months, low disease activity (CAS ≤ 3), was achieved in 88 eyes (92.6%) and TCZ was withdrawn in 29 cases due to low disease activity (n = 25) or inefficacy (n = 4). No serious adverse events were observed. In conclusion, TCZ is a useful and safe therapeutic option in refractory GO treatment.

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In the present study, we aimed to report our experience with rituximab (RTX) in the treatment of patients with ILD associated with AD (AD-ILD) at a single center. For this purpose, clinical characteristics, radiological findings, and pulmonary function tests (PFTs) of RTX-treated AD-ILD-patients seen from May 2016 until March 2020 at a referral center for individuals with ILD were retrospectively reviewed. Additionally, an updated literature review was conducted. A total of 26 patients (mean age 58.3 ± 11.1 years at ILD diagnosis) was included. The most common ADs related to ILD were systemic sclerosis, idiopathic inflammatory myositis (including anti-synthetase syndrome) and rheumatoid arthritis. Non-specific interstitial pneumonia (n = 12) and usual interstitial pneumonia (n = 11) were the predominant radiological patterns. The sustained improvement in PFTs was observed from the start of RTX, with a statistically significant increase in DLCO from basal to one year after RTX (mean + 4.2%, p = 0.024). Overall, there were no differences when comparing PFT outcome according to the radiological pattern or the specific type of AD. In conclusion, RTX constitutes a good therapeutic option to preserve lung function in patients with AD-ILD, regardless of the radiological pattern or the underlying AD.

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ObjectivesTo evaluate effectiveness and safety of certolizumab pegol (CZP) in uveitis due to immune-mediated inflammatory diseases (IMID).MethodsMulticentre study of CZP-treated patients with IMID uveitis refractory to conventional immunosuppressant. Effectiveness was assessed through the following ocular parameters: best-corrected visual acuity, anterior chamber cells, vitritis, macular thickness and retinal vasculitis. These variables were compared between the baseline, and first week, first, third, sixth months, first and second year.ResultsWe studied 80 (33 men/47 women) patients (111 affected eyes) with a mean age of 41.6±11.7 years. The IMID included were: spondyloarthritis (n=43), Behçet’s disease (n=10), psoriatic arthritis (n=8), Crohn’s disease (n=4), sarcoidosis (n=2), juvenile idiopathic arthritis (n=1), reactive arthritis (n=1), rheumatoid arthritis (n=1), relapsing polychondritis (n=1),ConclusionsCZP seems to be effective and safe in uveitis related to different IMID, even in patients refractory to previous biological drugs.

ObjectiveImmune checkpoint blockade therapy (ICBT) increases the anti-tumoural function of the immune system, but it can also induce immune-related adverse events (irAEs). Our aim was to assess the irAEs due to ICBT in patients from a single centre of Northern Spain. MethodsWe set up an observational study of patients treated in monotherapy with ICBT targeted against cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death 1 (PD-1) or its ligand (PD-L1) for solid organ tumours. All patients were followed up in a single University Hospital from March 2015 to September 2018. ResultsWe studied 102 patients (63 men/39 women); mean age 60.6±9.7 years, with lung (n=63), melanoma (n=21), kidney (n=11), gastric (n=3), colon (n=3) or bladder (n=1) cancer. Only 7 patients had a previous diagnosis of an immune-mediated disease, specifically: psoriasis (n=2), psoriatic arthritis (n=1), systemic lupus erythematosus (n=1), spondyloarthitis (n=1), rheumatoid arthritis (n=1) and cutaneous lupus (n=1). One of the following ICBT was administered: nivolumab (n=52), pembrolizumab (n=35), atezolizumab (n=10) and ipilimumab (n=5). After a mean follow-up time of 14.4±7.7 months since ICBT onset, 87 (85.3%) patients had experienced irAEs, mostly gastrointestinal, thyroid and musculskeletal manifestations including inflammatory arthralgia (n= 8), arthritis (n= 6) and myositis (n=2). ICBT was discontinued in 41 patients but it was reintroduced in 30 of them after resolution of the adverse event, with a good tolerance in all cases. Thirty-six (41.4%) of the 87 patients required specific treatment (prednisone, levothyroxine, and thiamazol) for the irAEs. Conclusion irAEs are frequent in patients undergoing ICBT. Almost half of the patients that have irAEs require treatment.Musculoskeletal manifestations are not uncommon.

Blau syndrome (BS) is an autoinflammatory disorder characterized by non-caseating granulomatous dermatitis, arthritis, and uveitis. We present a case of refractory and severe BS that was treated with the Janus kinase inhibitors (JAKINIBS), Tofacitinib (TOFA) and then Baricitinib (BARI). Our aim was to describe the clinical and immunological outcomes after treatment with JAKINIBS. Blood tests and serum samples were obtained during follow-up with TOFA and BARI. We assessed their effects on clinical outcomes, acute phase reactants, absolute lymphocyte counts (ALCs), lymphocyte subset counts, immunoglobulins, and cytokine levels. A review of the literature on the use of JAKINIBS for the treatment of uveitis and sarcoidosis was also conducted. TOFA led to a rapid and maintained disease control and a steroid-sparing effect. A decrease from baseline was observed in ALC, CD3+, CD4+, CD8+, and natural killer (NK) cell counts. B-cells were stable. Serum levels of interleukin (IL)-4 and tumor necrosis factor alpha (TNF-α) increased, whereas IL-2, IL-6, IL-10, and IL-17 maintained stable. TOFA was discontinued after 19 months due to significant lymphopenia. The initiation of BARI allowed maintaining adequate control of disease activity with an adequate safety profile. The literature review showed seven patients with uveitis and five with sarcoidosis treated with JAKINIBS. No cases of BS treated with JAKINIBS were found. We report the successful use of JAKINIBS in a patient with refractory and severe BS.