Intensive Treatment and Holiday of TNF-inhibitors in RA
Purpose of review: Biologics targeting tumor necrosis factor (TNF) has revolutionized the treatment of rheumatoid arthritis (RA) and clinical remission becomes a realistic treatment goal. After achieving remission, discontinuation of TNF inhibitors may become an important issue from viewing points of safety and economy. However, there is not well established firm evidence regarding biologic-free remission. We here document whether 'treatment holiday' of TNF inhibitors is possible in RA patients, after maintaining low disease activity by intensive treatment with TNF inhibitors.
Recent findings: From European studies such as BeSt and OPTIMA in patients with early RA and Japanese studies such as RRR and HONOR in patients with established RA, after reduction of disease activity to clinical remission or low disease activity in patients with RA by infliximab or adalimumab in combination with methotrexate, some patients could successfully remain in clinical remission without TNF inhibitors for 6 months or 1 year and without radiologic and functional progression of articular destruction.
Summary: After maintaining low disease activity by intensive treatment with TNF inhibitors, discontinuation of TNF inhibitors without disease flare, joint damage progression and functional impairment, treatment holiday, is possible in some RA patients.
Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic and destructive inflammatory synovitis and multiple organ manifestations that cause severe disability and mortality. Conventional disease-modifying antirheumatic drugs (DMARDs), most commonly methotrexate (MTX), remain the cornerstone of RA treatment. However, the use of MTX often fails to control disease activity and to prevent structural damage, and so more effective treatment strategies are needed.
Tumor necrosis factor (TNF) plays a pivotal role in the pathological processes of RA through the accumulation of inflammatory cells, the selfperpetuation of inflammation and induction and/or activation of osteoclasts, leading to cartilage and bone destruction and multiple organ manifestations. The combinational use of biologic products targeting TNF and MTX has revolutionized the treatment of RA, producing significant improvement in clinical, radiographic and functional outcomes that were not previously observed.
After clinical remission is induced, the remission has to be maintained as long as we can, which leads to structural and functional remission. However, in reality, the economic burden associated with expensive biological products and the longterm safety by inhibiting a particular cytokine remain unsolved. Thus, treatment strategies with TNF inhibitors targeting induction and/or maintenance of clinical remission can potentially lead to subsequent discontinuation of the TNF inhibitors. However, there is no well established firm evidence as to whether remission can be maintained even if a biologic agent is discontinued, namely, 'biologicfree remission'.
Here we document that 'treatment holiday' by the discontinuation of TNF inhibitors such as infliximab and adalimumab is possible in some RA patients, after obtaining low disease activity or clinical remission in a certain period by TNF inhibitors.
Abstract and Introduction
Abstract
Purpose of review: Biologics targeting tumor necrosis factor (TNF) has revolutionized the treatment of rheumatoid arthritis (RA) and clinical remission becomes a realistic treatment goal. After achieving remission, discontinuation of TNF inhibitors may become an important issue from viewing points of safety and economy. However, there is not well established firm evidence regarding biologic-free remission. We here document whether 'treatment holiday' of TNF inhibitors is possible in RA patients, after maintaining low disease activity by intensive treatment with TNF inhibitors.
Recent findings: From European studies such as BeSt and OPTIMA in patients with early RA and Japanese studies such as RRR and HONOR in patients with established RA, after reduction of disease activity to clinical remission or low disease activity in patients with RA by infliximab or adalimumab in combination with methotrexate, some patients could successfully remain in clinical remission without TNF inhibitors for 6 months or 1 year and without radiologic and functional progression of articular destruction.
Summary: After maintaining low disease activity by intensive treatment with TNF inhibitors, discontinuation of TNF inhibitors without disease flare, joint damage progression and functional impairment, treatment holiday, is possible in some RA patients.
Introduction
Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic and destructive inflammatory synovitis and multiple organ manifestations that cause severe disability and mortality. Conventional disease-modifying antirheumatic drugs (DMARDs), most commonly methotrexate (MTX), remain the cornerstone of RA treatment. However, the use of MTX often fails to control disease activity and to prevent structural damage, and so more effective treatment strategies are needed.
Tumor necrosis factor (TNF) plays a pivotal role in the pathological processes of RA through the accumulation of inflammatory cells, the selfperpetuation of inflammation and induction and/or activation of osteoclasts, leading to cartilage and bone destruction and multiple organ manifestations. The combinational use of biologic products targeting TNF and MTX has revolutionized the treatment of RA, producing significant improvement in clinical, radiographic and functional outcomes that were not previously observed.
After clinical remission is induced, the remission has to be maintained as long as we can, which leads to structural and functional remission. However, in reality, the economic burden associated with expensive biological products and the longterm safety by inhibiting a particular cytokine remain unsolved. Thus, treatment strategies with TNF inhibitors targeting induction and/or maintenance of clinical remission can potentially lead to subsequent discontinuation of the TNF inhibitors. However, there is no well established firm evidence as to whether remission can be maintained even if a biologic agent is discontinued, namely, 'biologicfree remission'.
Here we document that 'treatment holiday' by the discontinuation of TNF inhibitors such as infliximab and adalimumab is possible in some RA patients, after obtaining low disease activity or clinical remission in a certain period by TNF inhibitors.
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