Successful cessation of tumor necrosis factor inhibitor treatment in rheumatoid arthritis patients and potential predictors for early flare: An observational study in routine clinical care.

Objectives: To investigate the prevalence and the consequence of tumor necrosis factor inhibitor (TNFi) cessation after clinical improvement in rheumatoid arthritis (RA) patients in clinical practice and predictors of flare after TNFi cessation.Methods: We retrospectively assessed the prevalence of TNFi cessation after achieving sustained improvement, disease flare and joint damage progression after TNFi cessation in consecutive RA patients who started TNFi due to insufficient response to methotrexate were studied. Predictors for flare after TNFi cessation were investigated using Cox regression analysis.Results: In 135 patients who started TNFi with methotrexate, 95 stopped TNFi after sustained improvement and continued methotrexate thereafter. Over 1 year, 33 patients had a flare and 26 restarted TNFi therapy. In 78 patients whose radiographs adequate for evaluation were available, 73 did not exhibit joint damage progression. Female gender, smoking, the interval from starting methotrexate to starting TNFi of more than 9 months and glucocorticoid use at starting TNFi were independently associated with shorter time to flare.Conclusion: Sixty-five percent of patients were successfully discontinued TNFi over 1 year. Radiographic joint damage progression was rare. Early intervention with TNF inhibitor may contribute to successful TNF inhibitor cessation in patients with insufficient response to methotrexate.Key messageSuccessful TNF inhibitor cessation is achievable in two-third of RA patients after achieving sustained remission.Female gender and smoking may predispose to flare after TNF inhibitor cessation.Early intervention with TNF inhibitor may contribute to successful TNF inhibitor cessation.

Long-term efficacy and safety of add-on tacrolimus for persistent, active rheumatoid arthritis despite treatment with methotrexate and tumor necrosis factor inhibitors.

AIM: To assess the long-term efficacy and safety of adding tacrolimus for patients with active rheumatoid arthritis (RA) despite anti-tumor necrosis factor (TNF) therapy with methotrexate. METHODS: Consecutive patients who were treated with adding tacrolimus onto anti-TNF therapy with methotrexate for active RA despite anti-TNF therapy with methotrexate, were retrospectively analyzed in terms of treatment response, achieving remission, subsequent treatment tapering and adverse events. RESULTS: Fifteen patients could be analyzed. Median symptom duration was 2.9 years and prior duration of anti-TNF therapy was 40 weeks. Median value of Disease Activity Score in 28 joints was 4.6. Five, eight and two were on infliximab, etanercept and adalimumab at the onset of tacrolimus, respectively. At 2 years, the proportions of patients achieving responses of American College of Rheumatology 50, 70 and 90, were 80%, 73% and 40%, respectively, and those achieving remission as defined by Simplified Disease Activity Index ≤ 3.3 were 67%. All patients could discontinue oral glucocorticoids and 10 had been successfully withdrawn from anti-TNF therapy for more than 1 year at the final observation. CONCLUSION: Adding tacrolimus onto anti-TNF therapy is a promising therapeutic option with sustained benefit for refractory RA patients despite treatment with anti-TNF therapy combined with methotrexate.

Efficacy of add-on tacrolimus on methotrexate to maintain clinical remission after rediscontinuation of a tumor necrosis factor inhibitor in rheumatoid arthritis patients who relapsed shortly after discontinuation of the same tumor necrosis factor inhibitor due to clinical remission.

OBJECTIVES: To describe the efficacy of adding tacrolimus to maintain remission in patients with rheumatoid arthritis (RA) on methotrexate after discontinuation of tumor necrosis factor inhibitor (TNFi) therapy. METHODS: Consecutive patients with RA, who resumed a TNFi to treat flares after initial TNFi-free remission and discontinued a TNFi again after achieving remission and adding tacrolimus were enrolled. The lengths of remission after discontinuation of TNFi without or with tacrolimus were analyzed. RESULTS: Thirteen TNFi-free periods in six patients, in which seven were without and six were with tacrolimus were analyzed. All were seropositive females with a median age of 46 years and symptom duration of 1.2 years at the onset of TNFi therapy. Two were treated with infliximab and four were with etanercept. The median dose of tacrolimus was 2 mg/day with trough level of 4.5 ng/ml. The length of time to flare after discontinuation of TNFi therapy with tacrolimus was significantly longer than those without tacrolimus (median 107 weeks [range 4-207] versus 13 weeks [2-36]). After adding tacrolimus, only one patient resumed TNFi therapy and three had no flare until final observation. CONCLUSIONS: Add-on tacrolimus was effective in maintaining TNFi-free remission in patients with RA who ever relapsed after TNFi-free remission.