Influence of Social Support, Financial Status, and Lifestyle on the Disparity Between Inflammation and Disability in Rheumatoid Arthritis.

OBJECTIVE: To investigate how social support, financial status, and lifestyle influence the development of excess disability in rheumatoid arthritis (RA). METHODS: Data were obtained from the Étude et Suivi des Polyarthrites Indifférenciées Récentes (ESPOIR) cohort study of people with RA. A previous analysis identified groups with similar inflammation trajectories but markedly different disability over 10 years; those in the higher disability trajectory groups were defined as having "excess disability." Self-reported data regarding contextual factors (social support, financial situation, lifestyle) were obtained from participants, and they completed patient-reported outcome measures (pain, fatigue, anxiety, depression) at baseline. The direct effect of the contextual factors on excess disability and the effect mediated by patient-reported outcome measures were assessed using structural equation models. Findings were validated in 2 independent data sets (Norfolk Arthritis Register [NOAR], Early Rheumatoid Arthritis Network [ERAN]). RESULTS: Of 538 included ESPOIR participants (mean age ± SD 48.3 ± 12.2 years; 79.2% women), 200 participants (37.2%) were in the excess disability group. Less social support (ß = 0.17 [95% confidence interval (95% CI) 0.08, 0.26]), worse financial situation (ß = 0.24 [95% CI 0.14, 0.34]), less exercise (ß = 0.17 [95% CI 0.09-0.25]), and less education (ß = 0.15 [95% CI 0.06, 0.23]) were associated with excess disability group membership; smoking, alcohol consumption, and body mass index were not. Fatigue and depression mediated a small proportion of these effects. Similar results were seen in NOAR and ERAN. CONCLUSION: Greater emphasis is needed on the economic and social contexts of individuals with RA at presentation; these factors might influence disability over the following decade.

The Utility of Myositis Specific Antibodies in Clinical Practice.

BACKGROUND: Fifteen myositis-specific antibodies have been described and characterized over the past 40 years. Approximately two thirds of patients with idiopathic inflammatory myositis have a myositis-specific antibody and only rarely more than one. Assays to detect them are now widely available within clinical practice. CONTENT: We describe the original description and clinical phenotype of the myositis-specific antibodies, forming the antisynthetase syndrome group, anti-MDA-5 and rapidly progressive interstitial lung disease, anti-SRP/HMGCR and necrotizing myositis, anti-TIF-1γ/NXP-2 and malignancy, anti-SAE and esophageal disease, and anti-Mi-2 and classic dermatomyositis skin disease. SUMMARY: Clinical practice is likely to be refined, with diagnosis and classification of the idiopathic inflammatory myositides based primarily on myositis-specific antibody, rather than directed by muscle histology or the broader clinical characteristics of polymyositis and dermatomyositis. All patients newly presenting with idiopathic inflammatory myositis should be routinely screened for myositis-specific antibodies. A positive result will usefully provide diagnostic and prognostic information, guide selection of therapy, and prompt surveillance for potential organ involvement and other features, such as cancer, throughout the disease course.

Large joints are progressively involved in rheumatoid arthritis irrespective of rheumatoid factor status-results from the early rheumatoid arthritis study.

This study aimed to examine the progression of large joint involvement from early to established RA in terms of range of movement (ROM) and time to joint surgery, according to the presence of rheumatoid factor (RF). We used a historical longitudinal cohort of early RA patients. Patients were deemed RF negative if all repeated assessments were negative. The rate of progression from normal to any loss of range of movement (ROM) from years 3 to 14 were modelled using generalized estimating equations, for elbows, wrists, hips, knees and ankle, adjusting for confounders. Time to joint surgery was analysed using multivariable Cox models. A total of 1458 patients were included (66% female, mean age 55 years) and 74% were RF-positive. The prevalence of any loss of ROM, from year 3 through to 14 was highest in the wrist followed by ankle, knee, elbow and hip. Odds of loss of ROM increased over time in all joint regions assessed, at around 7-13% per year from year 3 to 14. Time to surgery was similar according to RF-status for the wrist and ankle, but RF-positive cases had a lower hazard of surgery at the elbow (HR 0.37, 0.15-0.90), hip (HR 0.69, 0.48-0.99) and after 10 years at the knee (HR 0.41, 0.25-0.68). Large joints become progressively involved in RA, most frequently affecting the wrist followed by ankle, which is overlooked in composite disease activity indices. RF-negative and positive cases progressed similarly. Treat-to-target approaches should be followed irrespective of RF status.

Secukinumab as a potential trigger of inflammatory bowel disease in ankylosing spondylitis or psoriatic arthritis patients.

OBJECTIVE: Real-world secukinumab gastrointestinal-related adverse events (GIRAE) data during treatment for AS and PsA are lacking. We aimed to obtain this through baseline evaluation of pre-existing IBD rates and predictors of GIRAE. METHODS: Patient electronic and paper records commencing secukinumab from 10 UK hospitals between 2016 and 2019 were reviewed. GIRAE after initiation were defined as: definite [objective evidence of IBD (biopsy proven), clear temporal association, resolution of symptoms on drug withdrawal, no alternative explanation felt more likely], probable (as per definite, but without biopsy confirmation) or possible (gastrointestinal symptoms not fulfilling definite or probable criteria). RESULTS: Data for all 306 patients started on secukinumab were analysed: 124 (40.5%) AS and 182 (59.5%) PsA. Twenty-four of 306 (7.8%) experienced GIRAE after starting secukinumab. Amongst patients who developed GIRAE, four (1.3%) had definite, seven (2.3%) probable and 13 (4.2%) possible IBD. All definite cases were patients with AS and stopped secukinumab; two had pre-existing IBD and two (0.7%) were de novo cases of which one required surgical intervention. Seven patients (2.3%) had pre-existing diagnoses of IBD prior to initiation, of which five patients experienced GIRAE. CONCLUSION: Absolute rates of new IBD in patients starting secukinumab are low. The majority of patients developing new GIRAE did not develop objective evidence of IBD or stop therapy. For patients with pre-existing IBD and AS the risk of GIRAE is much higher, and prescribing alternatives should be considered.

Discrete Trajectories of Resolving and Persistent Pain in People With Rheumatoid Arthritis Despite Undergoing Treatment for Inflammation: Results From Three UK Cohorts.

Rheumatoid arthritis (RA) is an example of human chronic inflammatory pain. Modern treatments suppress inflammation, yet pain remains a major problem for many people with RA. We hypothesized that discrete RA subgroups might display favorable or unfavorable pain trajectories when receiving treatment, and that baseline characteristics will predict trajectory allocation. Growth mixture modelling was used to identify discrete trajectories of Short Form-36 bodily pain scores during 3 years in 3 RA cohorts (Early RA Network (n = 683), British Society for Rheumatology Biologics Register Biologics (n = 7,090) and nonbiologics (n = 1,720) cohorts. Logistic regression compared baseline predictor variables between trajectories. The role of inflammation was examined in a subgroup analysis of people with normal levels of inflammatory markers after 3 years. The mean Short Form-36 bodily pain scores in each cohort improved but remained throughout 3 years of follow-up of >1 standard deviation worse than the UK general population average. Discrete persistent pain (59-79% of cohort participants) and resolving pain (19-27%) trajectories were identified in each cohort. In Early RA Network, a third trajectory displaying persistently low pain (23%) was also identified. In people with normal levels of inflammatory markers after 3 years, 65% were found to follow a persistent pain trajectory. When trajectories were compared, greater disability (adjusted odds ratio = 2.3-2.5 per unit baseline Health Assessment Questionnaire score) and smoking history (adjusted odds ratio = 1.6-1.8) were risk factors for persistent pain trajectories in each cohort. In conclusion, distinct trajectories indicate patient subgroups with very different pain prognosis during treatment for RA. Inflammation does not fully explain the pain trajectories, and noninflammatory factors as well as acute phase response predict which trajectory an individual will follow. Targeted treatments additional to those which suppress inflammation might reduce the long-term burden of arthritis pain. PERSPECTIVE: Immunosuppression decreases inflammation in RA, but pain outcomes are less favorable. Discrete persistent and resolving pain trajectories were identified after treatment, both in early and established RA. Smoking and greater disability at baseline predicted persistent pain. Identifying patient subgroups with a poor pain prognosis could enable adjunctive treatment to improve outcomes.

Medical arthroscopy: A tool for diagnosis and research in rheumatology.

Arthroscopy is an important diagnostic procedure which can be used in rheumatology practice to provide direct visualization of the joint cavity, permitting macroscopic evaluation of the synovium, sampling for histopathologic and microbiologic examination and the potential therapeutic benefit of lavage. The term 'medical arthroscopy' is used here to refer to arthroscopy performed by rheumatologists for these purposes. This term differentiates arthroscopy performed by orthopedic surgeons for structural interventions such as meniscal debridement and ligament repair. Medical arthroscopy finds a place in rheumatology as an aid to diagnosis, to confirm the presence of synovitis when not expected, to provide histologic or microbiologic diagnosis, and potential stratification for therapy, for example in rheumatoid arthritis, as well as a range of other research purposes. It is performed with local anesthetic using a small bore arthroscope, most usually inserted into the knee, although the wrist and metacarpophalangeal joints may also be inspected in this way. In experienced hands it is well tolerated, safe and complications are comparable to those reported by orthopedic surgeons.

Discordant inflammation and pain in early and established rheumatoid arthritis: Latent Class Analysis of Early Rheumatoid Arthritis Network and British Society for Rheumatology Biologics Register data.

BACKGROUND: Rheumatoid arthritis (RA) disease activity is often measured using the 28-joint Disease Activity Score (DAS28). We aimed to identify and independently verify subgroups of people with RA that may be discordant with respect to self-reported and objective disease state, with potentially different clinical needs. METHODS: Data were derived from three cohorts: (1) the Early Rheumatoid Arthritis Network (ERAN) and the British Society for Rheumatology Biologics Register (BSRBR), (2) those commencing tumour necrosis factor (TNF)-α inhibitors and (3) those using non-biologic drugs. In latent class analysis, we used variables related to pain, central pain mechanisms or inflammation (pain, vitality, mental health, erythrocyte sedimentation rate, swollen joint count, tender joint count, visual analogue scale of general health). Clinically relevant outcomes were examined. RESULTS: Five, four and four latent classes were found in the ERAN, BSRBR TNF inhibitor and non-biologic cohorts, respectively. The proportions of people assigned with >80% probability into latent classes were 76%, 58% and 72% in the ERAN, TNF inhibitor and non-biologic cohorts, respectively. The latent classes displayed either concordance between measures indicative of mild, moderate or severe disease activity; discordantly worse patient-reported measures despite less markedly elevated inflammation; or discordantly less severe patient-reported measures despite elevated inflammation. Latent classes with discordantly worse patient-reported measures represented 12%, 40% and 21% of the ERAN, TNF inhibitor and non-biologic cohorts, respectively; contained more females; and showed worse function. In those latent classes with worse scores at baseline, DAS28 and function improved over 1 year (p < 0.001 for all comparisons), and scores differed less at follow-up than at baseline. CONCLUSIONS: Discordant latent classes can be identified in people with RA, and these findings are robust across three cohorts with varying disease duration and activity. These findings could be used to identify a sizeable subgroup of people with RA who might gain added benefit from pain management strategies.

Biologic efficacy optimization--a step towards personalized medicine.

This following is a review of the factors that influence the outcome of biologic agents in the treatment of adult RA and, when synthesized into the clinical decision-making process, enhance optimization. Adiposity can exacerbate inflammatory diseases; patients with high BMI have worse outcomes from RA, including TNF inhibitors (TNFis), whereas the efficacy of abatacept and tocilizumab is unaffected. Smoking adversely affects TNFi outcomes but has less or no effect on the efficacy of rituximab and tocilizumab, and the effect on abatacept is unknown. Patients who are positive for ACPA and RF have better efficacy with rituximab and abatacept than those who are seronegative, whereas the influence of serotype is less significant for tocilizumab and more complex for TNFis. All biologics seem to do better when co-prescribed with MTX, whereas in monotherapy, tocilizumab is superior to adalimumab and prescription of a non-MTX DMARD has advantages over no DMARD for rituximab and adalimumab. Monitoring of TNFi drug levels is an exciting new field, correlating closely with efficacy in RA and PsA, and is influenced by BMI, adherence, co-prescribed DMARDs and anti-drug antibodies. The measurement of trough levels provides a potential tool for patients who are not doing well to determine early whether to switch within the TNFi class (if levels are low) or to a biologic with an alternative mode of action (if levels are normal or high). Conversely, the finding of supratherapeutic levels has the potential to enable individual patient selection for dose reduction without the risk of flare.

Predictors of change in bodily pain in early rheumatoid arthritis: an inception cohort study.

OBJECTIVE: To investigate possible predictors for lack of pain improvement after 1 year of treatment for early rheumatoid arthritis (RA). METHODS: The Early Rheumatoid Arthritis Network (ERAN) database was used for analysis of baseline and 1-year pain data. The ERAN is a hospital-based inception cohort of 1,189 people. Short Form 36 questionnaire bodily pain scores were used to calculate change in pain at 1 year as the outcome. The proportion of the Disease Activity Score in 28 joints (DAS28) attributable to patient-reported components (joint tenderness and visual analog scale score; DAS28-P) at baseline was derived as a predictor. Predictors of less improvement in pain were investigated using adjusted odds ratios (OR(adj) ) generated by logistic regression, adjusting for 14 additional clinical and demographic covariates. RESULTS: Greater pain at baseline was associated with sex, high DAS28, worse mental health, and smoking. Most patients with early RA reported incomplete improvement in bodily pain after 1 year. The DAS28-P index did not significantly change in the patients whose disease remained active. Less improvement in pain was predicted by female sex (OR(adj) 3.41, 95% confidence interval [95% CI] 1.35-8.64) and a high DAS28-P index at baseline (OR(adj) for tertiles 2.09, 95% CI 1.24-3.55). Other conventional RA risk factors did not predict pain changes. CONCLUSION: The factors most likely to predict less improvement in pain in early RA are female sex and a high DAS28-P index. A high DAS28-P index may reflect greater contributions of noninflammatory factors, such as central sensitization, to pain. Strategies in addition to inflammatory disease suppression may be required to adequately treat pain.