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Sustainable Efficacy of Switching From Intravenous to Subcutaneous Tocilizumab Monotherapy in Patients With Rheumatoid Arthritis.

ABSTRACT: To evaluate the efficacy and safety of switching from intravenous (IV) tocilizumab (TCZ) to subcutaneous (SC) TCZ monotherapy in rheumatoid arthritis patients.Patients who had completed 24 weeks of TCZ-SC (162 mg/2 weeks) or TCZ-IV (8 mg/kg/4 weeks) monotherapy in the double-blind period of the MUSASHI study were enrolled in an 84-week open-label extension period. All received TCZ-SC (162 mg/2 weeks) monotherapy. Effects of the IV to SC switch were evaluated at week 36 (12 weeks after switching).Overall, 319 patients received ?1 dose of TCZ-SC during the open-label extension period; 160 switched from TCZ-IV to TCZ-SC (TCZ IV/SC) and 159 continued TCZ-SC (TCZ SC/SC). Disease Activity Score in 28 joints using the erythrocyte sedimentation rate clinical remission rates were 62.5% (100 of 160) for TCZ IV/SC and 50.0% (79 of 158) for TCZ SC/SC at week 24, and were maintained at 62.5% (100 of 160) and 57.0% (90 of 158), respectively, at week 36. In the TCZ IV/SC group, 9% of patients (9 of 100) who had achieved remission at week 24 could not maintain remission at week 36. In TCZ IV/SC patients weighing ?70 kg, the percentage with a sufficient serum TCZ concentration (?1 ?g/ml) decreased from 90.9% (10 of 11) at week 24 to 45.5% (5 of 11) at week 36. Overall safety profiles were similar in TCZ IV/SC and TCZ SC/SC except for mild injection site reactions in TCZ IV/SC.Efficacy is adequately maintained in most patients switching from TCZ-IV (8 mg/kg/4 weeks) to TCZ-SC (162 mg/2 weeks) monotherapy. Patients receiving TCZ-IV can switch to TCZ-SC without serious safety concerns. Clinical efficacy may be reduced after switching in some patients with high body weight.

SUBMITTER: Ogata A

PROVIDER: S-EPMC5054840 | biostudies-other | 2015 Oct

REPOSITORIES: biostudies-other

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Sustainable Efficacy of Switching From Intravenous to Subcutaneous Tocilizumab Monotherapy in Patients With Rheumatoid Arthritis.

Ogata Atsushi A Atsumi Tatsuya T Fukuda Takaaki T Hirabayashi Yasuhiko Y Inaba Masaaki M Ishiguro Naoki N Kai Motokazu M Kawabata Daisuke D Kida Daihei D Kohsaka Hitoshi H Matsumura Ryutaro R Minota Seiji S Mukai Masaya M Sumida Takayuki T Takasugi Kiyoshi K Tamaki Shigenori S Takeuchi Tsutomu T Ueda Atsuhisa A Yamamoto Kazuhiko K Yamanaka Hisashi H Yoshifuji Hajime H Nomura Akira A

Arthritis care & research 20151001 10

<h4>Objective</h4>To evaluate the efficacy and safety of switching from intravenous (IV) tocilizumab (TCZ) to subcutaneous (SC) TCZ monotherapy in rheumatoid arthritis patients.<h4>Methods</h4>Patients who had completed 24 weeks of TCZ-SC (162 mg/2 weeks) or TCZ-IV (8 mg/kg/4 weeks) monotherapy in the double-blind period of the MUSASHI study were enrolled in an 84-week open-label extension period. All received TCZ-SC (162 mg/2 weeks) monotherapy. Effects of the IV to SC switch were evaluated at ...[more]

PMID: 25832859

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Project description:BackgroundThe treatment of rheumatoid arthritis is based on the use of disease-modifying antirheumatic drugs (DMARDs). Tocilizumab can be used as monotherapy or in combination with conventional synthetic DMARDs for the treatment of moderate-to-severe active rheumatoid arthritis. Subcutaneous (SC) and intravenous forms of the drug are available, but the SC form is more widely used.ObjectiveTo understand the real-world dose modification patterns of SC tocilizumab in the treatment of patients with rheumatoid arthritis in the United States.MethodsData were obtained from the Truven (now IBM) MarketScan and Optum Clinformatics databases. Patients were included if they had ≥1 pharmacy claims for SC tocilizumab and met other inclusion criteria. The mean, standard deviation, and median values were reported for the continuous variables, and frequency was reported for the categorical variables. Kaplan-Meier analysis was used to analyze the time to first dose modification. Logistic regression modeling was used to identify predictors of the likelihood of dose modification.ResultsThe study included 1266 patients in the Truven database and 512 patients in the Optum database who had commercial or Medicare Advantage or supplemental insurance. Of the patients who started treatment with biweekly SC tocilizumab (48% each in the Truven and Optum databases), 37% in Truven and 40% in Optum had dose escalation to a weekly dose. Of those who started weekly SC tocilizumab (43% in the Truven and 49% in the Optum databases), 3% (Truven) and 4% (Optum) had dose reduction. The remaining patients started alternative SC tocilizumab doses. Overall, 60% and 68% of patients in the Truven and Optum cohorts, respectively, initiated or escalated to the higher weekly dose of tocilizumab; the mean time to dose escalation was 126 days and 112 days, respectively. In the Truven cohort, corticosteroid use, age, and anemia were the main predictors for dose escalation. In the Optum cohort, female patients had increased odds of dose escalation compared with male patients.ConclusionThe dosing trends observed in this study show that physicians have taken advantage of the option to increase SC tocilizumab dosing, but only a few providers chose to reduce the dose. This trend in dose modification may increase the costs related to SC tocilizumab therapy.

Project description:Rheumatoid arthritis (RA) is a chronic systemic autoimmune condition which affects approximately 1% of the adult population worldwide and is characterized by joint inflammation, with extra-articular features being common. Interleukin 6 (IL-6) is one of the chief pro-inflammatory cytokines found in the joints and sera of patients with RA. Increased levels of IL-6 correlate with inflammation, disease activity, and radiological damage. RA treatment should focus on minimizing the signs and symptoms of disease (pain, stiffness, and swelling of the joints) and on preventing or minimizing joint damage to preserve functionality and quality of life. The benefits of early, intensive intervention are now acknowledged, with all patients with newly diagnosed, active RA being started on methotrexate (MTX) monotherapy or combination therapy. Lack of efficacy, intolerance, and/or toxicity can lead to discontinuation of this drug, and there is a need for exploring further treatment options. In the UK, patients with persistently high disease activity who have failed at least two conventional disease-modifying agents (DMARDs) including MTX may qualify for biologic therapy. Numerous trials have shown intravenous (IV) tocilizumab (TCZ), a biologic drug targeting and inhibiting IL-6, to be effective for controlling inflammation in RA, with an acceptable safety profile. Its superiority in monotherapy when compared with other biologic agents makes it the drug of choice for patients who are intolerant or have contraindications to traditional DMARDs. However, one of the drawbacks of IV TCZ is the requirement for monthly infusions, which is inherently inconvenient for the patient and associated with increased cost. Subcutaneous (SC) TCZ has now been approved following two clinical trials which showed similar efficacy and safety compared to IV TCZ, and better efficacy compared to placebo (SUMMACTA and BREVACTA trials, respectively). Respiratory infections are the most common side effects in patients receiving SC TCZ. Advantages of SC formulations include convenience and reduced cost compared with IV therapies. Overall, patients tend to have a preference for SC over IV administration of medications. Close monitoring of patients should be undertaken in all cases, paying particular attention to the full blood count, liver enzymes, and cholesterol levels.

Project description:OBJECTIVE:Most patients with rheumatoid arthritis (RA) strive to consolidate their treatment from methotrexate combinations. The objective of this analysis was to identify patients with RA most likely to achieve remission with tocilizumab (TCZ) monotherapy by developing and validating a prediction model and associated remission score. METHODS:We identified four TCZ monotherapy randomized controlled trials in RA and chose two for derivation and two for internal validation. Remission was defined as a Clinical Disease Activity Index score less than 2.8 at 24 weeks post randomization. We used logistic regression to assess the association between each predictor and remission. After selecting variables and assessing model performance in the derivation data set, we assessed model performance in the validation data set. The cohorts were combined to calculate a remission prediction score. RESULTS:The variables selected included younger age, male sex, lower baseline Clinical Disease Activity Index score, shorter RA disease duration, region of the world (Europe and South America [increased odds of remission] versus Asia and North America), no previous exposure to disease-modifying antirheumatic drugs and/or methotrexate, lower baseline Health Assessment Questionnaire Disability Index score, and baseline hematocrit. The area under the receiver operating characteristic curve was 0.739 in the derivation data set and 0.756 in the validation data set. Patients were categorized into three remission prediction categories based on the remission prediction score: 40% in the low (less than 10% probability of remission), 45% in the intermediate (10%-25% probability), and 15% in the moderate remission prediction category (greater than 25% probability). CONCLUSION:We used easily accessible factors to develop a remission prediction score to predict RA remission at 24 weeks after initializing TCZ monotherapy. These results may provide guidance to clinicians tailoring treatment options based on clinical characteristics.

Dataset Information

Sustainable Efficacy of Switching From Intravenous to Subcutaneous Tocilizumab Monotherapy in Patients With Rheumatoid Arthritis.

Publications

Sustainable Efficacy of Switching From Intravenous to Subcutaneous Tocilizumab Monotherapy in Patients With Rheumatoid Arthritis.

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