Tofacitinib (Xeljanz) is a potent, selective JAK inhibitor that preferentially inhibits Janus kinase (JAK) 1 and JAK3. In the EU, oral tofacitinib 5 mg twice daily is indicated for the treatment of moderate to severe active rheumatoid arthritis (RA) in adult patients who have responded inadequately to, or who are intolerant of, one or more DMARDs. Several clinical studies of ≤ 24 months' duration showed that tofacitinib monotherapy (as first- or second-line treatment) and combination therapy with a conventional synthetic DMARD (csDMARD; as second- or third-line treatment) was effective in reducing signs and symptoms of disease and improving health-related quality of life (HR-QOL), with benefits sustained during long-term therapy (≤ 96 months). Tofacitinib monotherapy inhibited progression of structural damage in methotrexate-naïve patients during ≤ 24 months' treatment, with beneficial effects also seen in patients receiving tofacitinib plus methotrexate as second-line therapy for 12 months. Tofacitinib was generally well tolerated during ≤ 114 months' treatment, with most adverse events of mild or moderate severity. The tolerability profile of tofacitinib was generally similar to that of biological DMARDs (bDMARDs), with infections and infestations the most common adverse events (AEs) in tofacitinib recipients. However, the incidence of herpes zoster (HZ) was higher with tofacitinib than in the general RA population, although infections were clinically manageable. When added to background methotrexate, tofacitinib was noninferior to adalimumab in terms of efficacy, and both combination therapies had generally similar tolerability profiles. Although additional comparative studies are needed to more definitively position tofacitinib relative to bDMARDs and other targeted synthetic DMARDs, current evidence indicates that oral tofacitinib is a useful option for the treatment of patients with RA.

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Epi proColon 2.0 CE is a blood-based test designed to aid in the early detection of colorectal cancer. The test comprises a qualitative assay for the polymerase chain reaction (PCR) detection of methylated Septin9 DNA, the presence of which is associated with colorectal cancer: however, positive results should be verified by colonoscopy or sigmoidoscopy. Epi proColon 2.0 CE discriminated between patients with colorectal cancer and healthy controls with high clinical sensitivity and specificity in pivotal case-control studies. The sensitivity of the test did not appear to be affected by the tumour location or by patient age or gender. In addition, limited data suggest that Epi proColon 2.0 CE discriminated between patients with colorectal cancer and healthy controls with higher sensitivity and generally similar specificity to that of the faecal immunochemical test, and with higher sensitivity and specificity to that of the guaiac-based faecal occult blood test (statistical data not available). In an observational study, most patients who refused colonoscopy for screening accepted a non-invasive test option as an alternative, and preferred Epi proColon 2.0 CE over a stool-based test. Large prospective trials of Epi proColon 2.0 CE in a screening setting will be required to further elucidate the cost-effectiveness of the test. Nevertheless, currently available data suggests that Epi proColon 2.0 CE has the potential to be a sensitive and convenient screening option for patients refusing screening by colonoscopy.

Palbociclib (Ibrance®) is an oral, reversible, selective, small-molecule inhibitor of cyclin-dependent kinases (CDK) 4 and CDK6 developed by Pfizer for the treatment of cancer. CDKs are important modulators of cell cycle entry and progression in response to growth signals, and inhibition of these kinases with palbociclib could enhance the activity of other anticancer drugs in tolerable regimens. Palbociclib, in combination with letrozole, was recently approved in the US for the first-line treatment of advanced breast cancer. Phase III development is underway worldwide investigating its use as first-line treatment in advanced breast cancer, as well as treatment of recurrent or advanced breast cancer and high-risk, early-stage breast cancer. A phase II trial is underway in the USA for non-small cell lung cancer under a US National Cancer Institute-funded research collaboration, and several phase I and II investigations are being conducted for various other solid tumour types and haematological malignancies. This article summarizes the milestones in the development of palbociclib leading to this first approval for use in postmenopausal women with estrogen-positive, human epidermal growth factor receptor (HER) 2-negative advanced breast cancer as initial endocrine-based therapy for their metastatic disease.

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Dapagliflozin (Forxiga ®) is a highly potent, reversible and selective sodium-glucose cotransporter-2 inhibitor indicated worldwide for the treatment of type 2 diabetes (T2D). In the EU, oral dapagliflozin once daily is approved for use as monotherapy (in patients who are intolerant of metformin) and as add-on combination therapy (with other glucose-lowering agents, including insulin) for T2D when diet and exercise alone do not provide adequate glycaemic control. In numerous well-designed clinical studies and their extensions, dapagliflozin as monotherapy and combination therapy with other antihyperglycaemic agents provided effective glycaemic control and reduced bodyweight and blood pressure (BP) across a broad spectrum of patients. Dapagliflozin reduced the rate of cardiovascular (CV) death or hospitalization for heart failure (HHF), did not adversely affect major adverse CV events (MACE) and possibly reduced progression of renal disease relative to placebo in patients with established atherosclerotic CV disease (CVD) or multiple risk factors for CVD. Dapagliflozin was generally well tolerated, with a low risk of hypoglycaemia; diabetic ketoacidosis (DKA), although rare, and genital infections were more common with dapagliflozin than placebo. Given its antihyperglycaemic, cardioprotective and possibly renoprotective properties and generally favourable tolerability profile, dapagliflozin provides an important option for the management of a broad patient population, regardless of the history of CVD.