Efficacy and safety of the biosimilar ABP 501 compared with adalimumab in patients with moderate to severe rheumatoid arthritis: a randomised, double-blind, phase III equivalence study.

OBJECTIVES: ABP 501 is a Food and Drug Administration-approved biosimilar to adalimumab; structural, functional and pharmacokinetic evaluations have shown that the two are highly similar. We report results from a phase III study comparing efficacy, safety and immunogenicity between ABP 501 and adalimumab. METHODS: In this randomised, double-blind, active comparator-controlled, 26-week equivalence study, patients with moderate to severe active rheumatoid arthritis (RA) despite methotrexate were randomised (1:1) to ABP 501 or adalimumab (40 mg) every 2 weeks. Primary endpoint was risk ratio (RR) of ACR20 between groups at week 24. Primary hypothesis that the treatments were equivalent would be confirmed if the 90% CI for RR of ACR20 at week 24 fell between 0.738 and 1.355, demonstrating that ABP 501 is similar to adalimumab. Secondary endpoints included Disease Activity Score 28-joint count-C reactive protein (DAS28-CRP). Safety was assessed via adverse events (AEs) and laboratory evaluations. Antidrug antibodies were assessed to determine immunogenicity. RESULTS: A total of 526 patients were randomised (n=264, ABP 501; n=262 adalimumab) and 494 completed the study. ACR20 response at week 24 was 74.6% (ABP 501) and 72.4% (adalimumab). At week 24, the RR of ACR20 (90% CI) between groups was 1.039 (0.954, 1.133), confirming the primary hypothesis. Changes from baseline in DAS28-CRP, ACR50 and ACR70 were similar. There were no clinically meaningful differences in AEs and laboratory abnormalities. A total of 38.3% (ABP 501) and 38.2% (adalimumab) of patients tested positive for binding antidrug antibodies. CONCLUSIONS: Results from this study demonstrate that ABP 501 is similar to adalimumab in clinical efficacy, safety and immunogenicity in patients with moderate to severe RA. TRIAL REGISTRATION NUMBER: NCT01970475; Results.

Humoral immune response to vaccines in patients with rheumatoid arthritis treated with tocilizumab: results of a randomised controlled trial (VISARA).

OBJECTIVE: To evaluate the effect of tocilizumab (TCZ), an interleukin 6 receptor inhibitor, on humoral immune responses to immunisations in patients with rheumatoid arthritis (RA). METHODS: Patients with RA with inadequate response/intolerance to one or more anti-tumour necrosis factor-α agents were randomly assigned (2:1) to TCZ 8 mg/kg intravenously every 4 weeks plus methotrexate (MTX) or MTX alone up until week 8. Serum was collected before vaccination at week 3, antibody titres were evaluated at week 8, and then all patients received TCZ+MTX through week 20. End points included proportion of patients responding to ≥6/12 pneumococcal polysaccharide vaccine (PPV23) serotypes (primary) and proportions responding to tetanus toxoid vaccine (TTV; secondary) at week 8. RESULTS: 91 patients were randomised. At week 8, 60.0% of TCZ+MTX and 70.8% of MTX patients responded to ≥6/12 PPV23 serotypes, with insufficient evidence for any difference in treatments (10.8% (95% CI -33.7 to 12.0)), and 42.0% and 39.1%, respectively, responded to TTV. Two of three TCZ+MTX patients with non-protective baseline TTV antibody titres achieved protective levels by week 8. The safety profile of TCZ was consistent with previous reports. CONCLUSIONS: Short-term TCZ treatment does not significantly attenuate humoral responses to PPV23 or TTV. To maximise vaccine response, patients should be up to date with immunisations before starting TCZ treatment. CLINICALTRIALSGOV IDENTIFIER: NCT01163747.

Discussion: DMARDs and biologic therapies in the management of inflammatory joint diseases.

Therapy for inflammatory joint diseases, such as rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis, includes various conventional disease-modifying antirheumatic drugs (DMARDs). These therapeutic agents are termed DMARDs because they have the potential to reduce or prevent joint damage and preserve joint integrity and function. Conventional DMARDs are used as monotherapy or in combination and include methotrexate, leflunomide, azathioprine, ciclosporin, hydroxychloroquine, sulfasalazine, gold and minocycline. Biologic response modifiers, which are based on proteins made by living cells, are newer agents available for the treatment of various inflammatory joint diseases. Biologic therapies now approved for use in inflammatory joint diseases are TNF inhibitors, T-cell modulators and B-cell depleters. They have all been shown to have clinical efficacy and are able to retard structural damage. However, all current immune-modulating therapies also have potential side effects, and the decision to use a particular agent for treatment should be based on a thorough discussion of the benefits and risks with the patient. Newer biologic response modifiers and other immunologic therapies are currently being developed for the treatment of inflammatory joint diseases and are discussed in this review.