Objective
To observe the efficacy and safety of tocilizumab combined with methotrexate (MTX) in the treatment of refractory adult-onset Still's disease (AOSD), and to explore whether it is possible to reduce the dose of tocilizumab when disease is under control.
Methods
Twenty-eight patients with refractory AOSD received the treatment of tocilizumab (8 mg/kg, Intravenous infusion every 4 weeks, and reduced to 8 mg/kg every 8 weeks after 6 months of remission) combined with MTX(12.5 mg oral intake per week). The clinical efficacy, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), ferritin level and dose change of glucocorticoid (GC) were observed prior to treatment initiation and 2, 4, 8, 12, 24, 36, 48 weeks after treatment. All adverse reactions were recorded. The Chi-square test and repetitive measure analysis of variance were used for statistical analysis.
Results
Compared with the baseline levels, our results showed that after 8-weeks of treatment with tocilizumab all patients had normal body temperature, while skin rash, joint swelling and pain disappeared. CRP [(125.4±48.3) mg/L, (6.1±2.5) mg/L vs (4.9±1.8) mg/L, F=77.034, P<0.01], ESR [(103±31) mm/1 h, (17±7) mm/1 h vs (16±4) mm/1 h, F=55.73, P<0.01], white blood cells count [(18.1±5.3)×109/L, (8.2±2.9)×109/L vs (7.2±2.1)×109/L, F=24.71, P<0.01], neutrophils count [(16.7±4.9)×109/L, (6.1±2.2)×109/L vs(4.9±2.3)×109/L, F=35.295, P<0.01], blood platelets [(312±83)×109/L, (199±40)×109/L vs (204±47)×109/L, F=7.139, P<0.01], hemoglobin [(100±9) g/L, (116±9) g/L vs (277±102) g/L, F=9.852, P<0.01], ferritin level [(3 542±1 313) ng/ml, (2 342±923) ng/ml vs (277±102) ng/ml) , F=34.232, P<0.01] were improved significantly, clinical symptoms and laboratory tests continued to improve at week 12, 24, 36 and 48, the dose of prednisone was reduced from (71.4±20.7) mg/d to (55.0±11.1) mg/d (P<0.05) After 2 weeks, and the dosage was gradually reduced to 3.3±2.1 mg/d (P<0.05) at the end of 48 weeks. Five (17.9%) patients discontinued prednisone after 36 weeks, and 7(25%) patients at week 48, no serious adverse events were found during the treatment.
Conclusion
Tocilizumab can rapidly and significantly improve clinical symptoms and laboratory tests of patients with refractory AOSD and it also can help with the reduction of GC dosage. In addition, the disease remains stable after the dose reduction of tombuzumab. The safety profile is good.
Key words:
Still's disease, adult-onset; Ttombuzumab; Methotrexate; Therapy
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Abstract Some patients have poor response to adult-onset Still disease (AOSD) traditional treatment, which easily recurs during the reduction of prednisone. We observed the efficacy and safety of tocilizumab combined with methotrexate (MTX) in the treatment of refractory AOSD, and to explore the possibility of reducing the dosage of tocilizumab after disease control. A total of 28 refractory AOSD cases who had an inadequate response to corticosteroids combined with at least 1 traditional immunosuppressive agent, and even large-dose prednisone could not relieve their conditions after recurrence, were selected in this study. They were treated with tocilizumab (intravenous 8 mg/kg) combined with MTX (oral 12.5 mg once a week). In detail, tocilizumab was firstly given every 4 weeks and after 6-month remission, it was then given every 8 weeks. Some items including body temperature, skin rash, joint swelling and pain, hepatosplenomegaly, blood routine, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), serum ferritin, and dosage of prednisone were observed before treatment as well as 2, 4, 8, 12, 24, 36, and 48 weeks after treatment. The adverse reactions occurring during the treatment were recorded. The body temperature was normal, the skin rash as well as joint swelling and pain disappeared, and laboratory indexes including CRP, ESR, white blood cell, neutrophilic granulocyte, platelet, hemoglobin, and ferritin were significantly improved after 8-week treatment (all P < .05). The clinical symptoms and laboratory indexes above mentioned were continuously improved 12, 24, 36, and 48 weeks after treatment. The mean dosage of prednisone was reduced from 71.4 ± 20.7 mg/day to 55.0 ± 11.1 mg/day after 2-week treatment, and to 3.3 ± 2.1 mg/day after 48-week treatment (all P < .05). Prednisone was discontinued in 5 cases after 36-week treatment and in 7 cases after 48-week treatment. No serious adverse reactions occurred during the treatment. Tocilizumab can rapidly and markedly improve the clinical symptoms and laboratory indexes and contribute to reduction and discontinuation of prednisone in refractory AOSD. The patients’ conditions are stable after reduction or discontinuation of prednisone and the tocilizumab possesses good safety.
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