Number of days required to measure sedentary time and physical activity using accelerometery in rheumatoid arthritis: a reliability study.

This study aimed to determine the minimum number of days required to reliably estimate free-living sedentary time, light-intensity physical activity (LPA) and moderate-intensity physical activity (MPA) using accelerometer data in people with Rheumatoid Arthritis (RA), according to Disease Activity Score-28-C-reactive protein (DAS-28-CRP). Secondary analysis of two existing RA cohorts with controlled (cohort 1) and active (cohort 2) disease was undertaken. People with RA were classified as being in remission (DAS-28-CRP < 2.4, n = 9), or with low (DAS-28-CRP ≥ 2.4-≤ 3.2, n = 15), moderate (DAS-28-CRP > 3.2-≤ 5.1, n = 41) or high (DAS-28-CRP > 5.1, n = 16) disease activity. Participants wore an ActiGraph accelerometer on their right hip for 7 days during waking hours. Validated RA-specific cut-points were applied to accelerometer data to estimate free-living sedentary time, LPA and MPA (%/day). Single-day intraclass correlation coefficients (ICC) were calculated and used in the Spearman Brown prophecy formula to determine the number of monitoring days required to achieve measurement reliability (ICC ≥ 0.80) for each group. The remission group required ≥ 4 monitoring days to achieve an ICC ≥ 0.80 for sedentary time and LPA, with low, moderate and high disease activity groups requiring ≥ 3 monitoring days to reliably estimate these behaviours. The monitoring days required for MPA were more variable across disease activity groups (remission = ≥ 3 days; low = ≥ 2 days; moderate = ≥ 3 days; high = ≥ 5 days). We conclude at least 4 monitoring days will reliably estimate sedentary time and LPA in RA, across the whole spectrum of disease activity. However, to reliably estimate behaviours across the movement continuum (sedentary time, LPA, MPA), at least 5 monitoring days are required.

The IL-23/IL-17A axis in spondyloarthritis: therapeutics informing pathogenesis?

PURPOSE OF REVIEW: To give an overview of the recently published trials relating to IL-23/IL-17 pathway in spondyloarthritis (SpA). RECENT FINDINGS: Recent studies in psoriasis confirmed the efficacy of targeting the IL-23/IL-17 pathway, with emerging evidence from head-to-head studies suggesting functional hierarchy of these inhibitors. In psoriatic arthritis (PsA), recent studies have indicated the efficacy of inhibiting IL-23p19, in addition to IL-23p40 and IL-17A, albeit all with lower hurdle results than those seen in psoriasis. The first head-to-head study of an IL-17A and tumour necrosis factor inhibitor in PsA has also recently been published. Recent studies have demonstrated the efficacy of the IL-17A inhibitor, ixekizumab, across the axial SpA spectrum. In contrast, inhibition of IL-12/IL-23p40 and IL-23p19 both failed in axial SpA. In inflammatory bowel disease (IBD), recent studies indicate efficacy of IL-23p40 and IL-23p19 inhibition, in contrast to the previous failed studies of IL-17 inhibition. SUMMARY: Clinical trials of IL-23/IL-17 inhibition have been transformative in psoriasis, with more mixed results in PsA and differential responses in axial SpA and IBD. These results pose challenges to our fundamental understanding of SpA pathogenesis and further head-to-head studies and more subtle evaluation of the local tissue-specific aspects will be required.

The potential value of blood monitoring of biologic drugs used in the treatment of rheumatoid arthritis.

The advent of biological therapies has been a major therapeutic advance in rheumatology. Many patients now enjoy improved quality of life through better disease control. The number of therapies continues to grow both within drug class (including biosimilar drugs) and via new mechanisms. For the first time, nonbiological drugs such as small-molecule inhibitors (Janus kinase inhibitors) have shown clinical equivalence. However, clinical unmet need remains with up to a third of patients commenced on a biologic therapy having minimal or no response: (a) Generally, the first biologic used secures the best response, with likelihood of remission falling thereafter with successive therapies; (b) the success of strategy trials using biological therapies can be difficult to replicate in clinical practice due to a combination of patient factors and service limitations. Accordingly, ensuring optimization of initial treatment is an important consideration before switching to alternatives. Therapeutic drug monitoring (TDM) is the measurement of serum levels of a biologic drug with the aim of improving patient care. It is usually combined with detection of any antidrug antibodies that could neutralize the effect of the therapy. This technology has the potential to be a form of 'personalized medicine' by individualizing therapy, in particular, dosing and likelihood of sustained treatment response. It requires a clear relationship between drug dose, blood concentration and therapeutic effect. This paper will outline the technology behind TDM and unpack what we can learn from our colleagues in gastroenterology, where the adoption of TDM is at a more advanced stage than in rheumatology. It will explore and set out a number of clinical scenarios where rheumatologists might find TDM helpful in day-to-day practice. Finally, an outline is given of international developments, including regulatory body appraisals and guideline development.