Methotrexate (MTX) has become the first-line treatment for rheumatoid (RA) and psoriatic arthritis (PsA); however, few studies have focused on its tolerability. The objective of our analyses was to study RA and PsA patients in whom MTX was discontinued, the reasons for this and the duration of MTX treatment prior to withdrawal. A retrospective electronic database review was undertaken to identify all patients who had received MTX for RA or PsA. Patients who had discontinued MTX were then identified, and the reasons for this were categorised. The duration of MTX treatment was assessed in those who had stopped treatment due to intolerability. A total of 1,257 patients who had received MTX were identified [762 (61 %) RA and 193 (15 %) PsA]. MTX had been stopped in 260 (34 %) patients with RA and 71 (36 %) patients with PsA most commonly due to gastrointestinal intolerability. The median duration of MTX treatment was 10 months in both groups, mean duration 21 and 18.6 months in RA and PsA groups, respectively. Overall, one third of patients with RA and PsA stop MTX most commonly due to poor tolerability. In the context of chronic disease, the median duration of treatment is short (10 months). Our analysis did not include patients who suffer from side effects but continue therapy; thus, the magnitude of the problem may be substantially greater therefore as poor tolerability impacts treatment adherence.

Background Biosimilar adalimumab became available in the UK in October 2018, with payers introducing a series of measures to drive the adoption of the ‘best value’ adalimumab.1 Consideration of value should include risk of loss of efficacy and adverse reactions, which might drive further biologic switches or ‘reverse switches’ to originator. Managing potential ‘nocebo effect’ requires high levels of patient engagement, whilst the presence or absence of citrate buffer may affect patient-reported discomfort, hence patient treatment perceptions. Methods Patients were switched to 2 different biosimilar adalimumabs, one buffered with citrate (ADA1) and one in a citrate-free buffer (ADA2). The choice of adalimumab biosimilar was made for clinical and economic reasons. Patients were informed of the switch to either ADA1 or ADA2 in advance via letter and at clinic visits. Patients who reported problems after switching were reviewed. Results A total of 744 patients were switched from originator adalimumab (ADA0) to ADA1 or ADA2. Rheumatology and dermatology patients were switched to ADA1, whilst gastroenterology patients were switched to ADA2, except for those with a latex allergy, where ADA1 was used (or ADA2 in a latex-free syringe). A total of 49 (6.6%) patients reported problems and a further switch of drug was judged necessary in 48 (Table 1). Switch failure was significantly more likely with ADA1 than ADA2 (7.7% vs. 1.8%; p = 0.006). The median time to switch failure was 97 days (range 5–196 days). The commonest reason for switch failure was disease flare (23 patients, 48%), followed by injection site pain or reaction (21 patients, 44%). Disease flare and injection site problems were more likely to be reported with ADA1 than ADA2 (flare: 23/583 vs. 0/161, p = 0.008; injection site pain 20/583 vs. 1/161, p = 0.06). For patients reporting disease flare, clinicians tended to select a reverse switch to ADA0, whilst for those with injection site problems, a further switch to a different biosimilar was the preferred approach; both strategies were effective at recapture. Conclusion In the context of an effective patient communication strategy, adalimumab biosimilar switching was associated with overall low rates of patient-reported problems in a large cohort. Despite an identical communication strategy, significantly higher rates of injection site problems and disease flares were seen between 2 different biosimilars, reflected in a higher need for further switches. These differences may impact the cost-effectiveness of any chosen strategy. Reference

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.Electronic supplementary materialThe online version of this article (doi:10.1007/s40744-014-0007-2) contains supplementary material, which is available to authorized users.