Background EULAR Task Force strongly discourage the use of bDMARDSs before trying a csDMARDs, particularly MTX. Maximisation of treatment effects includes reaching an optimal MTX dose within a few weeks and maintaining the maximal dose (25–30 mg weekly) for at least 8 weeks, before adding biologicals. Additionally Task Force recommends that all bDMARDs should be used preferentially in combination with MTX or other csDMARDs. But today there is lack of data confirming the efficacy of biologicals in patients in whom treatment with recommended high doses of MTX has failed.
Objectives The study aimed to assess the efficacy of some biologicals in patients in whom a treatment with recommended high doses of MTX failed.
Methods 122 pts (97 F, 25 M, aged 57±22 years, disease duration 10.1±5.2) with RA diagnosed acc to ACR 1987 criteria and high activity (DAS 28ESR >5.1) after 6 months of MTX treatment (at least 3 months with a dose 25-30 mg/week according to toleration) were included into an open study. In 74 pts etanercept 50 mg/each week, 19 adalimumab 40 mg/each second week, 4 infliximab 3 mg/kg.b.w. each 2nd month, 26 rituksymab 2x1.0 each 6th month were added. Following the EULAR treatment recommendations the number of RA remissions according to DAS28ESR (<2.6) was assessed after 3, 6, 9 months of treatment; follow-up was finished at month 15.
Results After 3 months 12 (9.8%), after 6 and 9 months 50 (41%), after 15 months 57 (46.7%) pts were in remission. There were no statistical differences between different biologicals. Important AE leading to treatment discontinuation was observed in 5 (4.1%) pts, skin reactions dominated. In a double blinded trials, MTX was used as background therapy in doses <15mg/w (ASPIRE) to <20 mg/w (TEMPO, PREMIER, LITHE), which allowed the treatment efficacy to be increased in reaching remission from 20 to 43%. The same efficacy was observed in the presented trial although pts were treated with higher doses of MTX. In CONCERTO trial a dose of 10 mg MTX or more a week appears to be effective and appropriate for use with adalimumab, but there was a statistically significant trend in the proportion of pts achieving DAS28CRP remission with increasing doses of MTX from 28% (MTX dose 2.5 mg/w) to 45% (20 mg/w). In our trial we did not observed evident additional effect of MTX doses higher than 20 mg/w. But our data strongly support the use of biological agents in combination with MTX what is recommended by the Task Force.
Conclusions The efficacy of biologicals started after the failure of optimal doses of MTX is very high, allowing a remission to be reached in nearly half of patients treated. It seems to that doses of MTH higher than 20 mg/w not increase efficacy, but this have to be confirmed by the further investigation.
Smolen J., Landewé R., Breedveld F. Et al.: EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis published online October 25, 2013 doi: 10.1136/annrheumdis-2013-204573,
Burmester G, Kivitz A, Kupper H, et al. Efficacy, pharmacokinetics, and safety of different doses of methotrexate in combination with adalimumab: results from the CONCERTO trial. Ann Rheum Dis 2013;72(Suppl 3):72.
Disclosure of Interest None declared
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