Clinical, functional and radiographic consequences of achieving stable low disease activity and remission with adalimumab plus methotrexate or methotrexate alone in early rheumatoid arthritis: 26-week results from the randomised, controlled OPTIMA study

Abstract

ObjectiveTo assess the efficacy and safety of adalimumab plus methotrexate (ADA+MTX) compared with methotrexate monotherapy in achieving stable low disease activity (LDA; disease activity score (DAS28(CRP)) <3.2 at weeks 22 and 26) and clinical, radiographic and functional outcomes in methotrexate-naive patients with early rheumatoid arthritis (RA).Methods1032 patients with active RA were randomly assigned 1:1 to ADA+MTX or placebo plus methotrexate (PBO+MTX) for 26 weeks. Treatment modifications were to be made in a subsequent study period based on the achievement of DAS28(CRP) <3.2 at weeks 22 and 26. Post-hoc analyses compared patients achieving stable remission using DAS28 and 2010 ACR/EULAR criteria with those achieving LDA but not remission.ResultsAmong patients completing 6 months, 44% (207/466) ADA+MTX versus 24% (112/460) PBO+MTX patients achieved stable LDA at weeks 22 and 26 (p<0.001). Combination therapy was statistically superior to methotrexate in obtaining higher ACR20/50/70 responses, more clinical remissions, greater mean reductions in DAS28(CRP), no radiographic progression, and normal functional status at week 26 (p<0.001 for all). The only factor predicting stable LDA was disease activity at week 12. Patients achieving ACR/EULAR remission, particularly in the PBO+MTX group, had some advantage in radiographic outcomes compared with patients who only achieved LDA (but not remission). The overall frequency of adverse events was comparable between groups. There were more serious infections and deaths in the ADA+MTX group, with a possible age effect.ConclusionsTreatment with ADA+MTX was significantly superior to methotrexate alone with respect to clinical, radiographic and functional outcomes in patients with early active RA. Before initiating treatment with adalimumab, individual patient evaluation of the benefit/risk ratio should be carefully considered.

Turkish Compliance and Adaptation of EULAR 2013 Recommendations for the Management of Rheumatoid Arthritis with Synthetic and Biological Disease-Modifying Antirheumatic Drugs: Expert Opinion of TLAR

“…Meanwhile, there are some studies suggesting that starting treatment with anti-TNF+MTX in early RA may provide good clinical results even when TNF inhibitor is withheld. 63,64 Rituximab has some advantages such that it can be used in patients with a recent history of lymphoma and demyelinating disease, latent tuberculosis, and patients who live in tuberculosisendemic regions. 20,30 Risk of serious infections with rituximab is similar with other biologics, most common ones being pneumonia, cellulitis, and urinary tract infections.…”

Patient‐Reported Outcomes From a Two‐Year Head‐to‐Head Comparison of Subcutaneous Abatacept and Adalimumab for Rheumatoid Arthritis

“…The AMPLE study design and patient inclusion/exclusion criteria have been described previously 13. Briefly, patients had active RA for ≤5 years, as defined by the 1987 ACR criteria for RA 15, had reported an inadequate response to MTX, were biologics‐naive, and had a Disease Activity Score in 28 joints using the C‐reactive protein (DAS28‐CRP) level ≥3.2.…”

“…The AMPLE (Abatacept versus Adalimumab Comparison in Biologic‐Naive RA Subjects with Background MTX) trial, the first head‐to‐head trial comparing biologic DMARDs in patients with RA receiving MTX, demonstrated noninferiority for abatacept versus adalimumab by the ACR 20% improvement response (ACR20) at year 1 (64.8% subcutaneous [SC] abatacept versus 63.4% adalimumab; estimated difference between treatments 1.8% [95% confidence interval (95% CI) −5.6, 9.2] in an intent‐to‐treat analysis) 12. In AMPLE, there was a similar time of onset of ACR20 response in both treatment groups, with the response maintained up to year 2 13.…”

Administration of TNF- Inhibitors for Rheumatoid Arthritis Therapy. Comments to the Results of a Meta-Analysis of Randomized Trials by N. Graudal et al.: Final or Thought Provoking Conclusions?

“…Практикующим ревматологам хорошо известны результаты рандоми-зированных контролируемых исследований, в которых доказана эффективность ГИБП в случаях неэффективно-сти/непереносимости стандартной терапии БМПП [4][5][6], в связи с чем результаты данного метаанализа вызывают некоторое удивление. Также в соответствии с рекоменда-циями EULAR (2013) по лечению ревматоидного артрита терапия ГИБП может применяться уже через 6 мес при неэффективности или непереносимости метотрексата или других небиологических БМПП при наличии небла-гоприятных факторов риска [7].…”