a) Purpose of Review: The intervertebral discs (IVD) are an essential component of the spine. Degeneration of the discs, commonly due to age or injury, is a leading cause of chronic lower back pain. Despite its high prevalence, there is no effective treatment for disc disease due to limited understanding of disc at the cellular and molecular level. b) Recent Findings: Recent research has demonstrated the importance of the intracellular developmental pathway sonic hedgehog (Shh) during the formation and postnatal maintenance of the IVD. Recent studies corroborate that the down-regulation of SHH expression is associated with pathological changes in the IVDs and demonstrate the reactivation of the hedgehog pathway as a promising avenue for rescuing health disc structure and function. c) Summary: Understanding the role of developmental signaling pathways that regulate disc formation and maintenance may help develop strategies to recapitulate the same mechanism for disc treatment and hence improve the quality and longevity of patient lives.

Objective To determine the risk of not being able to sustain remission after tapering MTX from targeted therapy in patients with controlled RA. Methods A systematic literature search was conducted in Medline, Embase and Cochrane Library for studies reporting remission outcomes after tapering MTX from targeted therapies in RA. Full-text articles and abstracts reported in English were included. Meta-analyses were conducted using random effects models. Forest and funnel plots were created. Results Ten articles were included. Studies evaluated MTX being tapered from combination treatment with TNF-inhibitors, tocilizumab, abatacept and tofacitinib. Nine studies were randomized and one was observational. Three out of 10 studies focused on early RA (<1 year). The MTX tapering strategy was gradual in 2 and rapid in 8 studies. Follow-up ranged from 3-18 months in randomized trials, and up to 3 years in the observational study. Our meta-analysis conducted in 2000 RA participants from 10 studies showed that patients who tapered MTX from targeted therapy had a 10% reduction in ability to sustain remission, an overall pooled RR 0.90 (95% CI 0.84, 0.97). There was no heterogeneity, (I2=0.0%, p=0.938). Our funnel plot indicated minimal publication bias. Conclusion Patients with controlled RA may taper MTX from targeted therapy with a 10% reduction in ability to sustain remission, for up to 18 months. Longer follow-up studies with attention to radiographic, functional and patient-reported outcomes are needed. The risk of disease worsening should be discussed with the patient with careful follow-up and prompt retreatment of disease worsening.

BackgroundImmune checkpoint inhibitors (ICI) can potentially cause ICI-inflammatory arthritis (ICI-IA), which often resembles rheumatoid arthritis (RA). In this study, we examined the degree of anticitrullinated peptide antibodies (ACPA) epitope expansion in CCP+ICI-IA and patients with RA.MethodsWe used clinical data and serum from ICI-IA and patients with RA with early disease as well as longstanding disease. A custom, bead-based antigen array was used to identify IgG ACPA reactivities to 18 putative RA-associated citrullinated proteins. Hierarchical clustering software was used to create a heatmap to identify ACPA levels. Additionally, HLA DRB1 typing was performed on ICI-IA patients as well as controls of patients treated with ICI that did not develop ICI-IA (ICI controls).ResultsCompared to patients with CCP+RA, patients with CCP+ICI-IA were older (p<0.001), less likely to have positive rheumatoid factor (p<0.001) and had a shorter duration of symptoms (p<0.001). There were less ACPA levels and a lower number of distinct ACPA epitopes in the serum of patients with ICI-IA compared with longstanding patients with RA (p<0.001). Among those tested for HLA DRB1, there were no differences in the frequency of the shared epitope between those with ICI-IA and ICI controls.ConclusionPatients with ICI-IA had lower ACPA titres and targeted fewer ACPA epitopes than longstanding patients with RA, and there were no significant differences in the presence of the shared epitope between those that developed ICI-IA and ICI controls. It remains to be determined if ICI-IA represents an accelerated model of RA pathogenesis with ICI triggering a transition from preclinical to clinical disease.