Pneumococcal vaccine uptake in patients with inflammatory arthritis: a single centre cohort study.

INTRODUCTION: Current guidelines recommend pneumococcal vaccination in individuals who are over the age of 65 or are immunosuppressed due to a disease or treatment. The objective of this study was to assess vaccine uptake rates in people with inflammatory arthritis for the pneumococcal, influenza and Covid-19 vaccines and factors determining uptake. METHODS: We conducted a retrospective single centre cohort study in the UK of individuals with rheumatoid arthritis, psoriatic arthritis and axial spondylarthritis between October and December 2023. Data were collected for age, gender, co-morbidities, immunosuppressive therapies, and dates of vaccines. Logistic regression was used to evaluate predictors of vaccine uptake, with adjustments for demographic and clinical factors. RESULTS: 906 individuals were identified. 46% were receiving treatment with csDMARD, 26% on biologic monotherapy, and 23% were on both biologic and csDMARDs. 316 individuals (35%) received a pneumococcal vaccine, lower than uptake for influenza (63%) and Covid-19 (87%) vaccines. Predictors of pneumococcal vaccine uptake included age, with older patients more likely to be vaccinated (odds ratio [OR] for age ≥ 65 years: 1.67, 95% CI 1.21-2.29). Those on biological therapy demonstrated higher likelihood of vaccination (OR for biologic therapy: 1.81, 95% CI 1.33-2.47). Additional Joint committee for immunisation and vaccination (JCVI) Green Book indicators also positively influenced vaccine uptake (OR: 1.67, 95% CI 1.19-2.33). CONCLUSION: Pneumococcal vaccine uptake in inflammatory rheumatic diseases is low, especially in younger patients and those not on biological therapy. The study highlights the need for a focused approach, distinct from strategies for other vaccines, to address this public health challenge.

OpenSAFELY: The impact of COVID-19 on azathioprine, leflunomide and methotrexate monitoring, and factors associated with change in monitoring rate.

AIMS: The COVID-19 pandemic created unprecedented pressure on healthcare services. This study investigates whether disease-modifying antirheumatic drug (DMARD) safety monitoring was affected during the COVID-19 pandemic. METHODS: A population-based cohort study was conducted using the OpenSAFELY platform to access electronic health record data from 24.2 million patients registered at general practices using TPP's SystmOne software. Patients were included for further analysis if prescribed azathioprine, leflunomide or methotrexate between November 2019 and July 2022. Outcomes were assessed as monthly trends and variation between various sociodemographic and clinical groups for adherence with standard safety monitoring recommendations. RESULTS: An acute increase in the rate of missed monitoring occurred across the study population (+12.4 percentage points) when lockdown measures were implemented in March 2020. This increase was more pronounced for some patient groups (70-79 year-olds: +13.7 percentage points; females: +12.8 percentage points), regions (North West: +17.0 percentage points), medications (leflunomide: +20.7 percentage points) and monitoring tests (blood pressure: +24.5 percentage points). Missed monitoring rates decreased substantially for all groups by July 2022. Consistent differences were observed in overall missed monitoring rates between several groups throughout the study. CONCLUSION: DMARD monitoring rates temporarily deteriorated during the COVID-19 pandemic. Deterioration coincided with the onset of lockdown measures, with monitoring rates recovering rapidly as lockdown measures were eased. Differences observed in monitoring rates between medications, tests, regions and patient groups highlight opportunities to tackle potential inequalities in the provision or uptake of monitoring services. Further research should evaluate the causes of the differences identified between groups.

Occupational impacts of early inflammatory arthritis: results from the National Early Inflammatory Arthritis Audit.

OBJECTIVES: Inflammatory arthritis (IA) causes significant work disability. Studies frequently fail to report important contextual information such as employment type. Our objective was to explore work participation, by gender and occupation type in early IA. METHODS: Data are from the National Early Inflammatory Arthritis Audit between 2018 and 2020. At diagnosis, clinicians collected information on demographics, IA disease activity and working status. Participants completed patient-reported outcomes at baseline, 3- and 12-months, including occupation and Work Productivity Activity Impairment (WPAI). Descriptive analyses of work participation and WPAI scores by occupational class at all timepoints were performed. Regression models examined associations between WPAI score and occupation. FINDINGS: 12 473 people received a diagnosis of IA and reported employment status, amongst whom 5,999 (47%) were in paid-work at least 20-h/week. At diagnosis, the working cohort had statistically significant lower measures of disease activity (p< 0.001). Occupation data were available for 3,694 individuals. At diagnosis, 2,793 completed a WPAI; 200 (7.2%) had stopped work and 344 (12.3%) changed jobs because of IA symptoms. There was a high burden of absenteeism (30%) and presenteeism (40%). Compared with managerial or professional workers, the burden of work disability was greater amongst those in routine (manual) occupations. During follow-up, 9.4% of WPAI completers had stopped work and 14.6% had changed roles. Work dropout occurred almost entirely amongst people doing routine jobs. CONCLUSION: IA associates with work disability within 12 months of diagnosis. It is easier to retain work in certain employment sectors. Participation in routine jobs is more affected, which may widen health inequalities.

Implementing treat-to-target urate-lowering therapy during hospitalisations for gout flares.

OBJECTIVES: To evaluate a strategy designed to optimise care and increase uptake of urate-lowering therapy (ULT) during hospitalisations for gout flares. METHODS: We conducted a prospective cohort study to evaluate a strategy that combined optimal in-hospital gout management with a nurse-led, follow-up appointment, followed by handover to primary care. Outcomes, including ULT initiation, urate target attainment, and re-hospitalisation rates, were compared between patients hospitalised for flares in the 12 months post-implementation and a retrospective cohort of hospitalised patients from 12 months pre-implementation. RESULTS: 119 and 108 patients, respectively, were hospitalised for gout flares in the 12 months pre- and post-implementation. For patients with 6-month follow-up data available (n = 94 and n = 97, respectively), the proportion newly initiated on ULT increased from 49.2% pre-implementation to 92.3% post-implementation (age/sex-adjusted odds ratio (aOR) 11.5; 95% confidence interval (CI) 4.36-30.5; p < 0.001). After implementation, more patients achieved a serum urate ≤360 micromol/L within 6 months of discharge (10.6% pre-implementation vs. 26.8% post-implementation; aOR 3.04; 95% CI 1.36-6.78; p = 0.007). The proportion of patients re-hospitalised for flares was 14.9% pre-implementation vs. 9.3% post-implementation (aOR 0.53, 95% CI 0.22 to 1.32; p = 0.18). CONCLUSION: Over 90% of patients were initiated on ULT after implementing a strategy to optimise hospital gout care. Despite increased initiation of ULT during flares, recurrent hospitalisations were not more frequent following implementation. Significant relative improvements in urate target attainment were observed post-implementation; however, for the majority of hospitalised gout patients to achieve urate targets, closer primary-secondary care integration is still needed.

Nonadherence to systemic immune-modifying therapy in people with psoriasis during the COVID-19 pandemic: findings from a global cross-sectional survey.

BACKGROUND: Nonadherence to immune-modifying therapy is a complex behaviour which, before the COVID-19 pandemic, was shown to be associated with mental health disorders in people with immune-mediated diseases. The COVID-19 pandemic has led to a rise in the global prevalence of anxiety and depression, and limited data exist on the association between mental health and nonadherence to immune-modifying therapy during the pandemic. OBJECTIVES: To assess the extent of and reasons underlying nonadherence to systemic immune-modifying therapy during the COVID-19 pandemic in individuals with psoriasis, and the association between mental health and nonadherence. METHODS: Online self-report surveys (PsoProtectMe), including validated screens for anxiety and depression, were completed globally during the first year of the pandemic. We assessed the association between anxiety or depression and nonadherence to systemic immune-modifying therapy using binomial logistic regression, adjusting for potential cofounders (age, sex, ethnicity, comorbidity) and country of residence. RESULTS: Of 3980 participants from 77 countries, 1611 (40.5%) were prescribed a systemic immune-modifying therapy. Of these, 408 (25.3%) reported nonadherence during the pandemic, most commonly due to concerns about their immunity. In the unadjusted model, a positive anxiety screen was associated with nonadherence to systemic immune-modifying therapy [odds ratio (OR) 1.37, 95% confidence interval (CI) 1.07-1.76]. Specifically, anxiety was associated with nonadherence to targeted therapy (OR 1.41, 95% CI 1.01-1.96) but not standard systemic therapy (OR 1.16, 95% CI 0.81-1.67). In the adjusted model, although the directions of the effects remained, anxiety was not significantly associated with nonadherence to overall systemic (OR 1.20, 95% CI 0.92-1.56) or targeted (OR 1.33, 95% CI 0.94-1.89) immune-modifying therapy. A positive depression screen was not strongly associated with nonadherence to systemic immune-modifying therapy in the unadjusted (OR 1.22, 95% CI 0.94-1.57) or adjusted models (OR 1.14, 95% CI 0.87-1.49). CONCLUSIONS: These data indicate substantial nonadherence to immune-modifying therapy in people with psoriasis during the pandemic, with attenuation of the association with mental health after adjusting for confounders. Future research in larger populations should further explore pandemic-specific drivers of treatment nonadherence. Clear communication of the reassuring findings from population-based research regarding immune-modifying therapy-associated adverse COVID-19 risks to people with psoriasis is essential, to optimize adherence and disease outcomes.

Diagnostic delay is common for patients with axial spondyloarthritis: results from the National Early Inflammatory Arthritis Audit.

OBJECTIVES: Updated guidelines for patients with axial SpA (axSpA) have sought to reduce diagnostic delay by raising awareness among clinicians. We used the National Early Inflammatory Arthritis Audit (NEIAA) to describe baseline characteristics and time to diagnosis for newly referred patients with axSpA in England and Wales. METHODS: Analyses were performed on sociodemographic and clinical metrics, including time to referral and assessment, for axSpA patients (n = 784) recruited to the NEIAA between May 2018 and March 2020. Comparators were patients recruited to the NEIAA with RA (n = 9270) or mechanical back pain (MBP; n = 370) in the same period. RESULTS: Symptom duration prior to initial rheumatology assessment was longer in axSpA than RA patients (P < 0.001) and non-significantly longer in axSpA than MBP patients (P = 0.062): 79.7% of axSpA patients had symptom durations of >6 months, compared with 33.7% of RA patients and 76.0% of MBP patients. Following referral, the median time to initial rheumatology assessment was longer for axSpA than RA patients (36 vs 24 days; P < 0.001) and similar to MBP patients (39 days; P = 0.30). Of the subset of patients deemed eligible for early inflammatory arthritis pathway follow-up, fewer axSpA than RA patients had disease education provided (77.5% vs 97.8%) and RA patients reported a better understanding of their condition and treatment. CONCLUSION: Diagnostic delay in axSpA remains a major challenge despite improved disease understanding and updated referral guidelines. Disease education is provided to fewer axSpA than RA patients, highlighting the need for specialist clinics and support programmes for axSpA patients.

The safety of JAK-1 inhibitors.

As efficacy and safety data emerge, differences between JAK inhibitor subclasses are appearing. JAK1 selective drugs, upadacitinib and filgotinib, have broadly come with the same overarching safety recommendations as other immunosuppressive drugs for RA: caution is needed regarding infection risk; monitoring for laboratory abnormalities, including lipids and muscle enzymes, is indicated. A distinguishing feature of JAK inhibitors is a risk for zoster reactivation. Numerically, overall rates of serious infection are similar among JAK inhibitor classes. There are currently no signals for diverticular perforation. VTE incidence rates were similar across comparator groups for the JAK1 selective agents. These observations are not yet conclusive evidence for different safety profiles between JAK1 selective agents and other JAK inhibitors. Differences in study population, design, and concomitant steroid use are examples of potential confounders. It is too early to draw conclusions on long-term outcomes such as malignancy and cardiovascular risk. Post-marketing pharmacovigilance studies will be essential.

A systematic review and network meta-analysis of the safety of early interventional treatments in rheumatoid arthritis.

OBJECTIVES: To evaluate the safety of treatment strategies in patients with early RA. METHODS: Systematic searches of MEDLINE, EMBASE and PubMed were conducted up to September 2020. Double-blind randomized controlled trials (RCTs) of licensed treatments conducted on completely naïve or MTX-naïve RA patients were included. Long-term extension studies, post-hoc and pooled analyses and RCTs with no comparator arm were excluded. Serious adverse events, serious infections and non-serious adverse events were extracted from all RCTs, and event rates in intervention and comparator arms were compared using meta-analysis and network meta-analysis (NMA). RESULTS: From an initial search of 3423 studies, 20 were included, involving 9202 patients. From the meta-analysis, the pooled incidence rates per 1000 patient-years for serious adverse events were 69.8 (95% CI: 64.9, 74.8), serious infections 18.9 (95% CI: 16.2, 21.6) and non-serious adverse events 1048.2 (95% CI: 1027.5, 1068.9). NMA showed that serious adverse event rates were higher with biologic monotherapy than with MTX monotherapy, rate ratio 1.39 (95% CI: 1.12, 1.73). Biologic monotherapy rates were higher than those for MTX and steroid therapy, rate ratio 3.22 (95% CI: 1.47, 7.07). Biologic monotherapy had a higher adverse event rate than biologic combination therapy, rate ratio 1.26 (95% CI: 1.02, 1.54). NMA showed no significant difference between strategies with respect to serious infections and non-serious adverse events rates. CONCLUSION: The study revealed the different risk profiles for various early RA treatment strategies. Observed differences were overall small, and in contrast to the findings of established RA studies, steroid-based regimens did not emerge as more harmful.

The use of real-world data to address questions of patient safety.

Pharmacovigilance registries of biologics were established to evaluate the risk of adverse events that may be missed in trials due to shorter durations and homogeneous samples. This review will present the strengths and weaknesses of registry data in addressing patient safety issues. Since their inception, scope has broadened because registries represent a relatively inexpensive approach to answering many clinical questions, both research and non-research focused. They achieve high statistical power, allow direct comparability, and offer a level of detail about adverse events not possible with trial data. Registries have been central in clarifying the risk of infection and malignancy with anti-TNF therapy, despite the limitations of selection and channelling bias, incomplete case capture, unmeasured confounding, and the inability to infer causality. Routinely collected data from electronic health records and national audits offer alternative real-world resources, further assisting patients and clinicians in understanding the risks of biologic therapy choices.

Is background methotrexate advantageous in extending TNF inhibitor drug survival in elderly patients with rheumatoid arthritis? An analysis of the British Society for Rheumatology Biologics Register.

OBJECTIVE: To evaluate drug survival with monotherapy compared with combination therapy with MTX in RA older adults. METHODS: Patients from the British Society for Rheumatology Biologics Register, a prospective observational cohort, who were biologic naïve and commencing their first TNF inhibitors (TNFi) were included. The cohort was stratified according to age: <75 and ≥75. Cox-proportional hazards models compared the risk of TNFi discontinuation from (i) any-cause, (ii) inefficacy and (iii) adverse events, between patients prescribed TNFi-monotherapy compared with TNFi MTX combination. RESULTS: The analysis included 15 700 patients. Ninety-five percent were <75 years old. Comorbidity burden and disease activity were higher in the ≥75 cohort. Fifty-two percent of patients discontinued TNFi therapy during the follow-up period. Persistence with therapy was higher in the <75 cohort. Patients receiving TNFi monotherapy were more likely to discontinue compared with patients receiving concomitant MTX [hazard rate 1.12 (1.06-1.18) P <0.001]. This finding only held true in patients <75 [hazard rate (HR) 1.11 (1.05-1.17) vs ≥75 [HR 1.13 (0.90-1.41)]. Examining TNFi discontinuation by cause revealed patients ≥75 receiving TNFi monotherapy were less likely to discontinue TNFi due to inefficacy [HR 0.66 (0.43-0.99) P=0.04] and more likely to discontinue therapy from adverse events [HR 1.41(1.02-1.96) P =0.04]. These results were supported by the multivariate adjustment in complete case and imputed analyses. CONCLUSION: TNFi monotherapy is associated with increased treatment failure. In older adults, the disadvantage of TNFi monotherapy on drug survival is no longer seen. Patients ≥75 have fewer discontinuations due to inefficacy than adverse events compared with younger patients. This likely reflects greater disposition to toxicity but perhaps also a decline in immunogenicity associated with immunosenescence.

The association between lymphopenia and serious infection risk in rheumatoid arthritis.

OBJECTIVES: To investigate the relationship between occurrence of serious infection (SI) and lymphocyte counts in patients with RA using data from a single centre. METHODS: We used routinely captured data from a single tertiary rheumatology centre to explore the relationship between lymphopenia and SI risk. Adult RA patients were included over a 5-year follow-up period. Admissions due to confirmed SI were considered. SI rate with 95% confidence intervals was calculated. The association between SI with baseline lymphocyte counts, time-averaged lymphocyte counts throughout all follow-up, and a nadir lymphocyte count was assessed using Cox proportional hazards regression. The relationship between lymphopenia over time and SI was analysed using a mixed-effect model of lymphocyte counts prior to SI. RESULTS: This analysis included 1095 patients with 205 SIs during 2016 person-years of follow-up. The SI rate was 4.61/100 patient-years (95% CI: 3.76, 5.65). Compared with patients with nadir lymphocyte counts >1.5 × 109 cells/l, nadir lymphopenia <1 × 109 cells/l was significantly associated with higher SI risk (HR 3.28; 95% CI: 1.59, 6.76), increasing to HR 8.08 (95% CI: 3.74, 17.44) in patients with lymphopenia <0.5 × 109 cells/l. Lymphocyte counts were observed to be reduced in the 30-day period prior to SI. CONCLUSION: Lymphocyte counts below <1.0 × 109 cells/l were associated with higher SI risk in RA patients; the strongest association between lymphopenia and SI was observed when lymphocyte counts were below <0.5 × 109 cells/l. Lymphopenia may be used as a measure to stratify patients at risk of SI.

Variation and implications of treatment decisions in early rheumatoid arthritis: results from a nationwide cohort study.

OBJECTIVES: Trial data have provided an evidence base to guide early treatment in RA. Few studies have investigated rheumatologists' adherence to guidelines, and subsequent impact on outcomes. The objectives of this study are to characterize baseline prescribing for patients with RA across the National Health Service, identifying treatment decisions that associate with patient outcomes. METHODS: A nationwide audit of RA collected information on treatment choices, DAS and sociodemographic factors at baseline. Treatment response was assessed at 3 months. Multilevel regression models were used to characterize departmental variations in prescribing. Heat maps were used to visualize geographical variation. Mixed effects regression models were constructed to assess the relationship between treatment decisions and disease outcomes, adjusting for patient and department level covariates. RESULTS: A total of 7154 patients with a diagnosis of RA were recruited from 136 departments. There was broad variation in prescribing choices, even between departments close to one another, with evidence of substantial deviation from guidelines. Over 75% of patients received glucocorticoids, fewer than half received combination conventional DMARDs. Early glucocorticoid therapy associated with achieving a good treatment response [odds ratio 1.93 (95% CI 1.31, 2.84), P-value = 0.001]. The association was maintained following propensity modelling and imputation. CONCLUSION: Guideline adherence varies between departments and cannot be explained by case-mix alone. Departments that prescribe early adjunctive steroid achieve better short-term outcomes. Further research should work to ensure that the early arthritis evidence base translates into better outcomes for patients.

Centre effects and case-mix in early rheumatoid arthritis observational cohorts: a narrative review.

OBJECTIVES: Observational cohort studies in early RA are a key source of evidence, despite inconsistencies in methodological approaches. This narrative review assesses the spectrum of methodologies used in addressing centre-level effect and case-mix adjustment in early RA observational cohort studies. METHODS: An electronic search was undertaken to identify observational prospective cohorts of >100 patients recruited from two or more centres, within 2 years of an RA or early inflammatory arthritis diagnosis. References and author publication lists of all studies from eligible cohorts were assessed for additional cohorts. RESULTS: Thirty-four unique cohorts were identified from 204 studies. Seven percent of studies considered centre in their analyses, most commonly as a fixed effect in regression modelling. Reporting of case-mix variables in analyses varied widely. The number of variables considered in case-mix adjustment was higher following publication of the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) statement in 2007. CONCLUSION: Centre effect is unreported or inadequately accounted for in the majority of RA observational cohorts, potentially leading to spurious inferences and obstructing comparisons between studies. Inadequate case-mix adjustment precludes meaningful comparisons between centres. Appropriate methodology to account for centre and case-mix adjustment should be considered at the outset of analyses.

A systematic review and meta-analysis of infection risk with small molecule JAK inhibitors in rheumatoid arthritis.

OBJECTIVES: To evaluate the risk of serious infection (SI) and herpes zoster (HZ) in rheumatoid arthritis patients receiving JAK inhibitors. METHODS: We conducted a systematic literature review and meta-analysis of phase II and III randomized controlled trials of tofacitinib (5 mg bid), baricitinib (4 mg od) and upadacitinib (15 mg od). Patient-exposure years were calculated. A per-protocol analysis was applied, incorporating follow-up time from patients randomized to placebo who cross into the treatment arm. Pooled incidence rates per 100 person-years of SI and HZ were calculated. Incidence rate ratios (IRRs) of drug vs placebo were compared using a meta-synthesis approach. RESULTS: Twenty-one studies were included in the meta-analysis; 11 tofacitinib (5888 patients), six baricitinib (3520 patients) and four upadacitinib studies (1736 patients). For SI, the incidence rates were 1.97 (95% CI: 1.41, 2.68), 3.16 (95% CI: 2.07, 4.63) and 3.02 (95% CI: 0.98, 7.04), respectively. The IRRs comparing treatment arm to placebo were statistically non-significant: 1.22 (95% CI: 0.60, 2.45), 0.80 (95% CI: 0.46, 1.38) and 1.14 (95% CI: 0.24, 5.43), respectively. For HZ, the incidence rates were 2.51 (95% CI: 1.87, 3.30), 3.16 (95% CI: 2.07, 4.63) and 2.41 (95% CI: 0.66, 6.18), respectively. The IRR of HZ comparing baricitinib with placebo was 2.86 (95% CI: 1.26, 6.50). Non-significant IRRs were seen with tofacitinib and upadacitinib: 1.38 (95% CI: 0.66, 2.88) and 0.78 (95% CI: 0.19, 3.22), respectively. Indicator opportunistic infections excluding HZ were too rare to provide meaningful incidence rates. CONCLUSION: The absolute SI rates were low. However across the JAK inhibitors, the incidence of HZ is higher than expected for the population (3.23 per 100 patient-years). While the risk was numerically greatest with baricitinib, indirect comparisons between the drugs did not demonstrate any significant difference in risk. SYSTEMATIC REVIEW REGISTRATION NUMBER: Prospero 2017 CRD4201707879.

Polypharmacy is associated with treatment response and serious adverse events: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis.

OBJECTIVE: To evaluate whether polypharmacy is associated with treatment response and serious adverse events (SAEs) in patients with RA using data from the British Society for Rheumatology Biologics Register (BSRBR-RA). METHODS: The BSRBR-RA is a prospective observational cohort study of biologic therapy starters and a DMARD comparator arm. A logistic regression model was used to calculate the odds of a EULAR 'good response' after 12 months of biologic therapy by medication count. Cox proportional hazards models were used to identify risk of SAEs. The utility of the models were compared with the Rheumatic Disease Comorbidity Index using Receiver Operator Characteristic and Harrell's C statistic. RESULTS: The analysis included 22 005 patients, of which 83% were initiated on biologics. Each additional medication reduced the odds of a EULAR good response by 8% [odds ratios 0.92 (95% CI 0.91, 0.93) P < 0.001] and 3% in the adjusted model [adjusted odds ratios 0.97 (95% CI 0.95, 0.98) P < 0.001]. The Receiver Operator Characteristic demonstrated significantly greater areas under the curve with the polypharmacy model than the Rheumatic Disease Comorbidity Index. There were 12 547 SAEs reported in 7286 patients. Each additional medication equated to a 13% increased risk of an SAE [hazard ratio 1.13 (95% CI 1.12, 1.13) P < 0.001] and 6% in the adjusted model [adjusted hazard ratio 1.06 (95% CI 1.05, 1.07) P < 0.001]. Predictive values for SAEs were comparable between the polypharmacy and Rheumatic Disease Comorbidity Index model. CONCLUSION: Polypharmacy is a simple but valuable predictor of clinical outcomes in patients with RA. This study supports medication count as a valid measure for use in epidemiologic analyses.

The new entries in the therapeutic armamentarium: The small molecule JAK inhibitors.

The past decade has witnessed an explosion in trial data on JAK inhibitors (JAKi). These small molecules target the Janus kinase - signal transducer and activator of transcription (JAK-STAT) pathway, blocking crucial cytokines across a septum of rheumatic diseases. As a class, JAKi are beginning to demonstrate efficacy on par, if not superior to biologics. Two first generation JAKi are licensed for use in inflammatory arthritis; tofacitinib and baricitinib. Next-generation JAKi have been designed with selective affinity for one JAK enzymes, the aim to reduce unwanted adverse effects without declining clinical efficacy. Emerging data with selective JAK1 inhibitors upadacitinib and filgotinib looks very promising. Despite differences in selectivity between JAKi, an overlap exists in their safety profiles. Across the class, a characteristic safety signal is emerging with viral opportunistic infections, particularly herpes zoster. Post marketing drug surveillance will be essential in evaluating the long-term risk with these agents.

A review of the musculoskeletal manifestations of sarcoidosis.

Sarcoidosis is a systemic disease of unknown aetiology that is characterized by granulomatous inflammation that can develop in almost any organ system. Musculoskeletal manifestations are seen in up to one-third of patients, ranging from arthralgia through to widespread destructive bone lesions. Inflammatory tendon lesions and periarticular swelling are more common than true joint synovitis. Despite advances in our understanding of the pathophysiology of the disease, diagnosis remains challenging. Definitive diagnosis, irrespective of organ site involvement, hinges on histological confirmation of non-caseating granuloma combined with an appropriate clinical syndrome. Musculoskeletal involvement usually develops early in the disease course. Imaging modalities, particularly fluorodeoxyglucose PET, are helpful in delineating the extent of involvement and measuring disease activity. Bone involvement may only become apparent following isotope imaging. Corticosteroids remain the cornerstone of treatment. MTX is the steroid-sparing agent of choice unless there is renal involvement. Biologic therapies are sometimes used in severe disease, although the evidence base for efficacy is inconsistent.