How do patient reported outcome measures affect treatment intensification and patient satisfaction in the management of psoriatic arthritis? A cross sectional study of 503 patients.

OBJECTIVES: The ASSIST study investigated prescribing in routine psoriatic arthritis (PsA) care and whether the patient reported outcome: PsA Impact of Disease questionnaire (PsAID-12), impacted treatment. This study also assessed a range of patient and clinician factors and their relationship to PsAID-12 scoring and treatment modification. METHODS: Patients with PsA were selected across the UK and Europe between July 2021-March 2022. Patients completed the PsAID questionnaire, with the results shared with their physician. Patient characteristics, disease activity, current treatment methods, treatment strategies, medication changes and patient satisfaction scores were recorded. RESULTS: 503 patients recruited. 36.2% had changes made to treatment, 88.8% of this had treatment escalation. Overall, the mean PsAID-12 score was higher for patients with treatment escalation; the PsAID-12 score was associated with odds of treatment escalation (OR: 1.58; p< 0.0001). However, most clinicians reported PsAID-12 did not impact their decision to escalate treatment, instead supporting treatment reduction decisions. Physician's assessment of disease activity had the most statistically significant effect on likelihood of treatment escalation, (OR = 2.68, per 1-point score increase). Escalation was more likely in patients not treated with biologic therapies. Additional factors associated with treatment escalation included: patient characteristics, physician characteristics, disease activity and disease impact. CONCLUSION: This study highlights multiple factors impacting treatment decision making for individuals with PsA. PsAID-12 scoring correlates with multiple measures of disease severity and odds of treatment escalation. However, most clinicians reported the PsAID-12 did not influence treatment escalation decisions. PsAID scoring could be used to increase confidence in treatment de-escalation.

An international multi-centre analysis of current prescribing practices and shared decision-making in psoriatic arthritis.

OBJECTIVES: Shared decision-making (SDM) is advocated to improve patient outcomes in Psoriatic arthritis (PsA). We analysed current prescribing practices and the extent of SDM in PsA across Europe. METHODS: The ASSIST study was a cross-sectional observational study of PsA patients aged ≥18 years attending face-to-face appointments between July 2021-March 2022. Patient demographics, current treatment and treatment decisions were recorded. SDM was measured by the clinician's effort to collaborate (CollaboRATE questionnaire) and patient communication confidence (PEPPI-5 tool). RESULTS: 503 patients were included from 24 centres across the UK, France, Germany, Italy and Spain. Physician- and patient-reported measures of disease activity were highest in the UK. Conventional synthetic DMARDs constituted a higher percentage of current PsA treatment in UK than continental Europe (66.4% vs 44.9%), which differed from biologic DMARDs (36.4% vs 64.4%). Implementing treatment escalation was most common in the UK. CollaboRATE and PEPPI-5 scores were high across centres. Of 31 patients with low CollaboRATE scores (<4.5), no patients with low PsAID-12 scores (<5) had treatment escalation. However, of 465 patients with CollaboRATE scores ≥4.5, 59 patients with low PsAID-12 scores received treatment escalation. CONCLUSIONS: Higher rates of treatment escalation seen in the UK may be explained by higher disease activity and a younger cohort. High levels of collaboration in face-to-face PsA consultations suggests effective implementation of the SDM approach. Our data indicate that, in patients with mild disease activity, only those with higher perceived collaboration underwent treatment escalation. Prospective studies should examine the impact of SDM on PsA patient outcomes. TRIAL REGISTRATION: clinicaltrials.gov, NCT05171270.

Efficacy and safety of obinutuzumab in systemic lupus erythematosus patients with secondary non-response to rituximab.

OBJECTIVES: Secondary inefficacy with infusion reactions and anti-drug antibodies (secondary non-depletion nonresponse, 2NDNR) occurs in 14% of SLE patients receiving repeated rituximab courses. We evaluated baseline clinical characteristics, efficacy and safety of obinutuzumab, a next-generation humanized type-2 anti-CD20 antibody licensed for haematological malignancies in SLE patients with 2NDNR to rituximab. METHODS: We collated data from SLE patients receiving obinutuzumab for secondary non-response to rituximab in BILAG centres. Disease activity was assessed using BILAG-2004, SLEDAI-2K and serology before, and 6 months after, obinutuzumab 2× 1000 mg infusions alongside methylprednisolone 100 mg. RESULTS: All nine patients included in the study received obinutuzumab with concomitant oral immunosuppression. At 6 months post-obinutuzumab, there were significant reductions in median SLEDAI-2K from 12 to 6 (P = 0.014) and total BILAG-2004 score from 21 to 2 (P = 0.009). Complement C3 and dsDNA titres improved significantly (both P = 0.04). Numerical, but not statistically significant improvements were seen in C4 levels. Of 8/9 patients receiving concomitant oral prednisolone at baseline (all >10 mg/day), 5/8 had their dose reduced at 6 months. Four of nine patients were on 5 mg/day and were in Lupus Low Disease Activity State following obinutuzumab. After obinutuzumab, 6/9 patients with peripheral B cell data achieved complete depletion, including 4/4 assessed with highly sensitive assays. Of the nine patients, one obinutuzumab non-responder required CYC therapy. One unvaccinated patient died from COVID-19. CONCLUSIONS: Obinutuzumab appears to be effective and steroid-sparing in renal and non-renal SLE patients with secondary non-response to rituximab. These patients have severe disease with few treatment options but given responsiveness to B cell depletion, switching to humanized type-2 anti-CD20 therapy is a logical approach.

The effect of smoking on outcomes following primary total hip and knee arthroplasty: a population-based cohort study of 117,024 patients.

Background and purpose - Smoking is a modifiable risk factor that may adversely affect postoperative outcomes. Healthcare providers are increasingly denying smokers access to total hip and knee arthroplasty (THA and TKA) until they stop smoking. Evidence supporting this is unclear. We assessed the effect of smoking on outcomes following arthroplasty.Patients and methods - We identified THAs and TKAs from the Clinical Practice Research Datalink, which were linked with datasets from Hospital Episode Statistics and the Office for National Statistics to identify outcomes. The effect of smoking on postoperative outcomes (complications, medications, revision, mortality, patient-reported outcome measures [PROMs]) was assessed using adjusted regression models.Results - We studied 60,812 THAs and 56,212 TKAs (11% smokers, 33% ex-smokers, 57% non-smokers). Following THA, smokers had an increased risk of lower respiratory tract infection (LRTI) and myocardial infarction compared with non-smokers and ex-smokers. Following TKA, smokers had an increased risk of LRTI compared with non-smokers. Compared with non-smokers (THA relative risk ratio [RRR] = 0.65; 95% CI = 0.61-0.69; TKA RRR = 0.82; CI = 0.78-0.86) and ex-smokers (THR RRR = 0.90; CI = 0.84-0.95), smokers had increased opioid usage 1-year postoperatively. Similar patterns were observed for weak opioids, paracetamol, and gabapentinoids. 1-year mortality rates were higher in smokers compared with non-smokers (THA hazard ratio [HR] = 0.37, CI = 0.29-0.49; TKA HR = 0.52, CI = 0.34-0.81) and ex-smokers (THA HR = 0.53, CI = 0.40-0.70). Long-term revision rates were not increased in smokers. Smokers had improvement in PROMs compared with preoperatively, with no clinically important difference in postoperative PROMs between smokers, non-smokers, and ex-smokers.Interpretation - Smoking is associated with more medical complications, higher analgesia usage, and increased mortality following arthroplasty. Most adverse outcomes were reduced in ex-smokers, therefore smoking cessation should be encouraged before arthroplasty.

Genome-wide association study of response to methotrexate in early rheumatoid arthritis patients.

Methotrexate (MTX) monotherapy is a common first treatment for rheumatoid arthritis (RA), but many patients do not respond adequately. In order to identify genetic predictors of response, we have combined data from two consortia to carry out a genome-wide study of response to MTX in 1424 early RA patients of European ancestry. Clinical endpoints were change from baseline to 6 months after starting treatment in swollen 28-joint count, tender 28-joint count, C-reactive protein and the overall 3-component disease activity score (DAS28). No single nucleotide polymorphism (SNP) reached genome-wide statistical significance for any outcome measure. The strongest evidence for association was with rs168201 in NRG3 (p = 10-7 for change in DAS28). Some support was also seen for association with ZMIZ1, previously highlighted in a study of response to MTX in juvenile idiopathic arthritis. Follow-up in two smaller cohorts of 429 and 177 RA patients did not support these findings, although these cohorts were more heterogeneous.

Relationship between area-level socio-economic deprivation and autoantibody status in patients with rheumatoid arthritis: multicentre cross-sectional study.

OBJECTIVES: The aims of this study were to assess the association between area-level socio-economic deprivation and the phenotype of rheumatoid arthritis (RA), defined by rheumatoid factor (RF) and anticitrullinated peptide antibody (AC PA) status, and to determine whether any observed association can be explained by smoking. METHODS: The authors performed logistic regression analysis of 6298 patients with RA, defined by American College of Rheumatology classification criteria modified for genetic studies. Analysis was stratified by cohort/recruitment centre. Socio-economic deprivation was measured using the Townsend Index. RESULTS: Deprivation predicted RF but not ACPA positivity, independent of smoking. The ORs for trend across tertiles, adjusted for smoking, gender, period of birth and cohort/recruitment centre, were 1.14 (95% CI 1.01 to 1.29) for RF and 1.01 (95% CI 0.87 to 1.16) for ACPA. Even after adjusting for deprivation, smoking was strongly associated with ACPA positivity (OR 1.38, 95% CI 1.22 to 1.55). There was no evidence of any effect modification by the RA risk alleles (HLA-DRB1 shared epitope and PTPN22 rs2476601) that have previously been shown to modify the effect of smoking on ACPA and RF positivity. CONCLUSIONS: Among patients with RA, deprivation predicted RF positivity but not ACPA positivity. The effect of deprivation did not appear to be explained by smoking. Deprivation may be a marker for previously unrecognised, potentially modifiable environmental influences on the immunological phenotype of RA. Furthermore, given the known associations of RF positivity with prognosis and response to treatment in RA, these findings have potential implications for resource allocation and healthcare delivery.

Measuring Physical Function in Psoriatic Arthritis: Comparing the Multidimensional Health Assessment Questionnaire to the Health Assessment Questionnaire-Disability Index.

OBJECTIVE: To compare physical function scales of the Multidimensional Health Assessment Questionnaire (MDHAQ) with that of the Health Assessment Questionnaire-Disability Index (HAQ-DI) in patients with psoriatic arthritis (PsA), and to examine whether either questionnaire is less prone to "floor effects." METHODS: Data were collected prospectively from 2018 to 2019 across 3 UK hospitals. All patients completed physical function scales within the MDHAQ and HAQ-DI in a single clinic visit. Agreement was assessed using medians and the Bland-Altman method. Intraclass correlation coefficients (ICCs) were used to assess test-retest reliability. RESULTS: Two hundred ten patients completed the clinic visit; 1 withdrew consent. Thus, 209 were analyzed. Sixty percent were male, with mean age of 51.7 years and median disease duration of 7 years. In clinic, median MDHAQ and HAQ-DI including/excluding aids scores were 0.30, 0.50, and 0.50 respectively. Although the median score for HAQ-DI was higher than for MDHAQ, the difference between the 2 scores was mostly within 1.96 SDs from the mean, suggesting good agreement. The ICCs demonstrated excellent test-retest reliability for both the MDHAQ and HAQ-DI. Similar numbers of patients scored 0 on the MDHAQ and HAQ-DI including/excluding aids (48, 47, and 49, respectively). Using a score of ≤ 0.5 as a cutoff for minor functional impairment, 23 patients had a MDHAQ ≤ 0.5 when their HAQ-DI including aids was > 0.5. Conversely, 4 patients had a MDHAQ > 0.5 when the HAQ-DI including aids was ≤ 0.5. CONCLUSION: Both the MDHAQ and HAQ-DI appear to be similar in detecting floor effects in patients with PsA.

Comparing the Visual Analog Scale and the Numerical Rating Scale in Patient-reported Outcomes in Psoriatic Arthritis.

OBJECTIVE: Patient self-report scales are invaluable in psoriatic arthritis (PsA), as they allow physicians to rapidly assess patient perspectives of disease activity. We aimed to assess the agreement of the visual analog scale (VAS), a 100-mm horizontal line, and the numerical rating scale (NRS), a 21-point scale ranging from 0 to 10 in increments of 0.5, in patients with PsA. METHODS: Data were collected prospectively across 3 UK hospital trusts from 2018 to 2019. All patients completed the VAS and NRS for pain, arthritis, skin psoriasis (PsO), and global disease activity. A subset completed an identical pack 1 week later. Demographic and clinical data were also collected. Agreement was assessed using medians and the Bland-Altman method. Intraclass correlation coefficients (ICCs) were used to assess test-retest reliability. Spearman rank correlation coefficients were used to assess dependency between scale scores and clinical variables. RESULTS: Two hundred ten patients completed the study; 1 withdrew consent. Thus, 209 were analyzed. For pain, arthritis, skin PsO, and global disease activity, the difference between the VAS and NRS lay mostly within 1.96 SD of the mean, suggesting reasonable agreement between the 2 scales. Among the patients, 64.1% preferred the NRS. The ICCs demonstrated excellent test-retest reliability for both VAS and NRS. Higher VAS and NRS scores were associated with increased tender/swollen joint count, poorer functional status, and greater life impact. CONCLUSION: The VAS and NRS show reasonable agreement in key patient-reported outcomes in PsA. Results from both scales are correlated with disease severity and life impact.

Effect of Fatigue, Older Age, Higher Body Mass Index, and Female Sex on Disability in Early Rheumatoid Arthritis in the Treatment-to-Target Era.

OBJECTIVE: To compare disease activity and disability over 2 years in early rheumatoid arthritis (RA) before and after implementation of treat-to-target therapy and identify predictors of adverse outcome. METHODS: The Yorkshire Early Arthritis Register (YEAR) recruited 725 patients with early RA between 2002 and 2009, treated with a step-up approach. The Inflammatory Arthritis Continuum study (IACON) recruited cases between 2010 and 2014 and treated to target. A total of 384 IACON cases met 2010 American College of Rheumatology/European League Against Rheumatism criteria. Latent growth curves of change in Disease Activity Score in 28 joints (DAS28) and the Health Assessment Questionnaire (HAQ) were compared between YEAR and IACON. Latent class growth analysis identified trajectories of change. Baseline predictors of trajectories were identified using logistic regression. RESULTS: The mean DAS28 over 2 years was lower in IACON than in YEAR. Latent trajectories of HAQ change in YEAR were high stable (21% of cohort), moderate reducing (35%), and low reducing (44%). Only moderate reducing (66%) and low reducing (34%) were seen in IACON. In both cohorts, female sex and fatigue predicted adverse HAQ trajectories (high stable and moderate reducing). Odds ratios (ORs) for moderate reducing compared to low reducing for women were 2.58 (95% confidence interval [95% CI] 1.69, 4.49) in YEAR and 5.81 (95% CI 2.44, 14.29) in IACON. ORs per centimeter fatigue visual analog score were 1.13 (95% CI 1.07, 1.20) in YEAR and 1.16 (95% CI 1.12, 1.20) in IACON. CONCLUSION: Treat-to-target therapy gave more favorable trajectories of change in DAS28 and HAQ, but adverse HAQ trajectory was more likely in women with greater fatigue, suggesting such patients would benefit from interventions to improve function as well as reduce inflammation.

Comorbidities in Anti-Cyclic Citrullinated Peptide Positive At-Risk Individuals Do Not Differ from Those Patients with Early Inflammatory Arthritis.

OBJECTIVES: To compare comorbidities in a cohort of cyclic citrullinated peptide (CCP) antibody positive patients without or prior to onset of inflammatory arthritis (IA) to those in patients with early IA. METHODS: Baseline data from two established cohorts were used. The first recruited people at risk of IA: CCP antibody positive cases without IA (CCP Cohort, n = 296). The second cohort [the Inflammatory Arthritis CONtinuum study (IACON)] recruited patients with early IA (n = 725). Proportions of patients with given comorbidities were compared between cohorts and then logistic regression was used to determine odds ratios (OR) for the CCP cohort having specific comorbidities, compared to IACON patients. Analyses adjusted for gender, age, smoking status, and body mass index. RESULTS: Patients from the CCP cohort were younger (mean age 50, compared to 53 years). The proportion of patients with at least one comorbidity was higher in the IACON than the CCP cohort: (40% compared to 24%, respectively). Results of logistic regression analyses suggested the odds of hypertension, taking a lipid-lowering agent, ischemic heart disease, cerebrovascular disease, lung disease, and diabetes were not increased in either cohort. However, patients in the CCP cohort were more likely to be taking an antidepressant (OR = 1.62, 95% CI 1.03, 2.56, p = 0.037). CONCLUSION: There was no significant difference in comorbidities among people with CCP antibodies but without IA, compared to those of patients with established IA.

Patient-reported Outcomes as Predictors of Change in Disease Activity and Disability in Early Rheumatoid Arthritis: Results from the Yorkshire Early Arthritis Register.

OBJECTIVE: To assess patient-reported variables as predictors of change in disease activity and disability in early rheumatoid arthritis (RA). METHODS: Cases were recruited to the Yorkshire Early Arthritis Register (YEAR) between 1997 and 2009 (n = 1415). Predictors of the 28-joint Disease Activity Score (DAS28) and the Health Assessment Questionnaire-Disability Index (HAQ-DI) at baseline and change over 12 months were identified using multilevel models. Baseline predictors were sex, age, symptom duration, autoantibody status, pain and fatigue visual analog scales (VAS), duration of early morning stiffness (EMS), DAS28, and HAQ-DI. RESULTS: Rates of change were slower in women than men: DAS28 fell by 0.19 and 0.17 units/month, and HAQ-DI by 0.028 and 0.023 units/month in men and women, respectively. Baseline pain and EMS had small effects on rates of change, whereas fatigue VAS was only associated with DAS28 and HAQ-DI at baseline. In patients recruited up to 2002, DAS28 reduced more quickly in those with greater pain at baseline (by 0.01 units/mo of DAS28 per cm pain VAS, p = 0.024); in patients recruited after 2002, the effect for pain was stronger (by 0.01 units/mo, p = 0.087). DAS28 reduction was greater with longer EMS. In both cohorts, fall in HAQ-DI (p = 0.006) was greater in patients with longer EMS duration, but pain and fatigue were not significant predictors of change in HAQ-DI. CONCLUSION: Patient-reported fatigue, pain, and stiffness at baseline are of limited value for the prediction of RA change in disease activity (DAS28) and activity limitation (HAQ-DI).

Saddle-nose deformities in the rheumatology clinic.

Saddle-nose deformity can occur as a result of trauma to the nose, but it has also been well described in the setting of infections such as leprosy and syphilis and idiopathic inflammatory conditions such as granulomatosis with polyangiitis (formerly known as Wegener granulomatosis) and relapsing polychondritis. Since these deformities may also arise without an evident precipitating cause, they can pose a diagnostic conundrum. We review 2 cases of saddle-nose deformity that were treated at Northwick Park Hospital in Middlesex, England. The first patient was a 53-year-old woman who presented with epistaxis and deviation of the nasal septum. She subsequently developed a saddle-nose deformity and a septal ulcer. An autoimmune screen was negative, and histologic findings were nonspecific. She underwent successful reconstruction with a polyethylene implant. The second patient was a 21-year-old woman who presented with nasal obstruction and a nasal septal deviation. Two years later, she was diagnosed with Crohn disease and treatment with azathioprine was commenced. Eventually, the cartilaginous dorsum of her nose collapsed. A biopsy of the area revealed nonspecific, active, chronic inflammation. A polyethylene implant was placed to correct the deformity, but part of the implant became dislodged, and revision surgery was not successful. A subsequent revision was performed, and the early results were encouraging. Saddle-nose deformity may be a manifestation of underlying connective tissue disease, so it is important to detect and treat any such condition before embarking on surgical repair of the deformity. Our 2 cases indicate that this very deforming condition is poorly understood and treatment can be unsatisfactory.

MTHFR functional genetic variation and methotrexate treatment response in rheumatoid arthritis: a meta-analysis.

AIM: To date, functional MTHFR SNPs have been tested for their impact on low-dose methotrexate (MTX) response in small rheumatoid arthritis (RA) cohorts. We sought to test their effect in the single largest cohort studied to date, and undertook a meta-analysis utilizing stringent study inclusion criteria. MATERIALS & METHODS: RA patients treated with MTX monotherapy from the Yorkshire Early Arthritis Register (YEAR) were genotyped using RFLP assays, and tested for association with treatment efficacy. Studies for meta-analysis were screened by a set of stringent inclusion criteria. RESULTS & CONCLUSION: rs1801131 and rs1801133 were not associated with response to MTX in the YEAR cohort, nor did they affect the probability of achieving a low disease activity state. A meta-analysis of comparable studies found no association with these SNPs. MTHFR SNPs rs1801131 and rs1801133 are unlikely to have a clinically meaningful effect on the first 6 months of MTX treatment in early RA.

Metaanalysis of the association of smoking and PTPN22 R620W genotype on autoantibody status and radiological erosions in rheumatoid arthritis.

OBJECTIVE: To investigate the interrelationships among smoking, protein tyrosine phosphatase non-receptor 22 (PTPN22) R620W (rs2476601) genotype, and anticitrullinated peptide antibody (ACPA) status; and among smoking, PTPN22 R620W genotype, and presence of bone erosions overall and separately by ACPA status in patients with rheumatoid arthritis (RA). METHODS: Six studies totaling 2680 patients with RA were included in a Mantel-Haenszel fixed-effects metaanalysis investigating ACPA status and up to 8 studies totaling 3172 patients with RA were included in a Mantel-Haenszel fixed-effects metaanalysis investigating presence of erosive damage. RESULTS: Evidence was found for an increase in the odds of ACPA positivity for ever smoking (OR 1.56, 95% CI 1.28-1.90, p = 8.5 × 10(-6)), carriage of at least 1 of the PTPN22 risk alleles (OR 1.50, 95% CI 1.13-2.00, p = 5.5 × 10(-3)) and both ever smoking and carriage of at least 1 of the PTPN22 risk alleles (OR 2.22, 95% CI 1.69-2.91, p = 8.3 × 10(-9)). There was no evidence of an association between presence of erosive damage and smoking status or carriage of PTPN22 risk alleles when analyzed overall or separately by ACPA status. CONCLUSION: This metaanalysis indicates that both smoking and the PTPN22 risk allele are associated with the risk of ACPA positivity. There was insufficient evidence to establish a relationship in either direction between PTPN22 and smoking with erosive damage, despite evidence that ACPA positivity is associated with erosive damage.

Purification and characterisation of an antifreeze protein from Forsythia suspensa (L.).

Recrystallisation inhibition (RI) activity has been isolated from cold-acclimated Forsythia suspensa bark and leaves, which is stable when boiled, and not sensitive to reducing agents. The antifreeze activity has been purified to a single 20 kDa protein, using anion exchange, hydroxyapatite chromatography, and gel filtration. The protein is abundant in forsythia bark with 0.5microg pure protein obtained from 35 g bark. RI activity is seen with as little as 6 microg ml(-1) protein. Sequence homology was seen with dehydrins, and forsythia AFP contains the Y-segment, a conserved region found in many dehydrins.