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ObjectiveTo explore anxiety and self-isolation in patients with inflammatory rheumatic disease (IRD)15 months into the coronavirus disease 2019 (COVID-19) pandemic, including attitudes toward and effects of SARS-CoV-2 vaccination.MethodsA nationwide online survey was conducted at 3 timepoints: May 2020, November 2020, and May 2021. Patients with IRD followed in the Danish Rheumatology Quality Registry (DANBIO) were asked about the effects of the pandemic, including SARS-CoV-2 infection and their behavior, anxiety, and concerns. The May 2021 survey included attitudes toward SARS-CoV-2 and influenza vaccination. Characteristics associated with self-isolation in May 2021 were explored with adjusted logistic regression analyses that included patient characteristics and SARS-CoV-2 vaccination status.ResultsRespondents to surveys 1, 2, and 3 included 12,789; 14,755; and 13,921 patients, respectively; 64% had rheumatoid arthritis and 63% were female. Anxiety and concerns were highest in May 2020 and decreased to stable levels in November 2020 and May 2021; 86%, 50%, and 52% of respondents reported self-isolation, respectively. In May 2021, 4% of respondents self-reported previous SARS-CoV-2 infection. The SARS-CoV-2 vaccine acceptance rate was 86%, and the proportion of patients vaccinated against influenza had increased from 50% in winter 2019-2020 to 64% in winter 2020-2021. The proportion of patients with anxiety appeared similar among those vaccinated and unvaccinated against SARS-CoV-2. In multivariable analyses, being unvaccinated, female gender, receiving biologic drugs, and poor quality of life were independently associated with self-isolation.ConclusionLevels of anxiety and self-isolation decreased after the initial lockdown period in patients with IRD. Half of the patients reported self-isolation in May 2021, a phase that included widespread reopening of society and large-scale vaccination. The lack of prepandemic data prevented a full understanding of the long-term effects of the pandemic on anxiety and self-isolation in patients with IRD.

ObjectiveTo investigate the distribution of patient-reported outcomes (PROs) in patients with axial spondyloarthritis (axSpA) initiating a tumor necrosis factor inhibitor (TNFi), to assess the proportion reaching PRO "remission" across registries and treatment series, and to compare patients registered to fulfill the modified New York (mNY) criteria for ankylosing spondylitis (AS) vs patients with nonradiographic axSpA (nr-axSpA).MethodsFifteen European registries contributed PRO scores for pain, fatigue, patient global assessment (PtGA), Bath Ankylosing Spondylitis (AS) Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), and Health Assessment Questionnaire (HAQ) from 19,498 patients with axSpA. Changes in PROs and PRO remission rates (definitions: ≤ 20 mm for pain, fatigue, PtGA, BASDAI, and BASFI; ≤ 0.5 for HAQ) were calculated at 6, 12, and 24 months of treatment.ResultsHeterogeneity in baseline characteristics and outcomes between registries were observed. In pooled data, 6 months after the start of a first TNFi, pain score was reduced by approximately 60% (median at baseline/ 6/12/24 months: 65/25/20/20 mm) in patients on treatment. Similar patterns were observed for fatigue (68/32/30/25 mm), PtGA (66/29/21/20 mm), BASDAI (58/26/21/19 mm), BASFI (46/20/16/16 mm), and HAQ (0.8/0.4/0.2/0.2). Patients with AS (n = 3281) had a slightly better response than patients with nr-axSpA (n = 993). The Lund Efficacy Index (LUNDEX)-adjusted remission rates at 6 months for pain/fatigue/PtGA/BASDAI/BASFI/HAQ were 39%/30%/38%/34%/35%/48% for the AS cohort and 30%/21%/26%/24%/33%/47% for the nr-axSpA cohort. Better PRO responses were seen with a first TNFi compared to a second and third TNFi.ConclusionPatients with axSpA starting a TNFi achieved high PRO remission rates, most pronounced in those fulfilling the mNY criteria and for the first TNFi.

Objective.The RAMRIS [Outcome Measures in Rheumatology rheumatoid arthritis (RA) magnetic resonance imaging (MRI) Scoring system] is used in clinical RA trials. We have investigated methods to combine the RAMRIS features into valid and responsive scores for inflammation and joint damage.Methods.We used data from 3 large randomized early RA trials to assess 5 methods to develop a combined score for inflammation based on RAMRIS bone marrow edema, synovitis, and tenosynovitis scores, and a combined joint damage score based on erosions and joint space narrowing. Methods included unweighted summation, normalized summation, and 3 different variants of weighted summation of the RAMRIS features. We used a derivation cohort to calculate summation weights to maximize the responsiveness of the combined score. Construct validity of the combined scores was examined by assessing correlations to imaging, clinical, and biochemical measures. Responsiveness was tested by calculating the standardized response mean (SRM) and the relative efficiency of each score in a validation cohort.Results.Patient characteristics, as well as baseline and followup RAMRIS scores, were comparable between cohorts. All combined scores were significantly correlated to other imaging, clinical, and biochemical measures. Inflammation scores combined by normalized and weighted summation had significantly higher responsiveness in comparison to unweighted summation, with SRM (95% CI) for unweighted summation 0.62 (0.51–0.73), normalized summation 0.73 (0.63–0.83), and weighted summation 0.74 (0.64–0.84). For the damage score, there was a trend toward higher responsiveness for weighted summation.Conclusion.Combined MRI scores calculated by normalized or weighted summation of individual MRI pathologies were valid and responsive.

Objective.By linkage of national registries, we investigated the risk of longterm sickness absence (LTSA) ≥ 3 weeks in a large cohort of Danish patients with rheumatoid arthritis (RA) and non-patients. The study aimed to (1) estimate the risk of LTSA for patients with RA compared with the general population, (2) examine whether the risk of LTSA has changed in recent years, and (3) evaluate the effect of other risk factors for LTSA (e.g., physical work demands, age, sex, education, and psychiatric and somatic comorbidities).Methods.A total of 6677 patients with RA aged 18–59 years in the years 1994–2011 were identified in registries and compared with 56,955 controls from the general population matched by age, sex, and city size. The risk of LTSA was analyzed using Cox proportional hazards models with late entry, controlling for other risk factors and assuming separate risks in the first year after diagnosis and the following years.Results.Compared with the general population, patients with RA had increased risk of LTSA in the first year after diagnosis (HR 5.4 during 1994–1999, 95% CI 4.2–6.8) and in following years (HR 2.4, 95% CI 2.1–2.8). For established RA (> 1 yr after diagnosis), the excess was 20% lower in 2006–2011 (HR 1.9, 95% CI 1.7–2.2) compared with 1994–1999 (p < 0.001). For patients with RA and controls, older age, shorter education, a physically demanding job, and somatic and/or psychiatric comorbidities increased the risk of LTSA.Conclusion.While improvements were observed from 1994–1999 to 2006–2011, patients with RA have significant increased risk of LTSA, in particular in the first year after diagnosis.

Objective.To investigate sex differences in response to anti-tumor necrosis factor-α (TNF-α) therapy over time in early versus established rheumatoid arthritis (RA).Methods.Patients with RA who initiated anti-TNF therapy between January 2003 and June 2008 in Denmark were selected from the DANBIO Registry. Sex differences in baseline disease features were examined using chi-square, Mann-Whitney U tests, and t tests. Using a generalized estimating equations (GEE) model for repeated measures, we examined European League Against Rheumatism (EULAR) responses in men and women over 48 months of followup, adjusting for baseline values of age, 28-joint Disease Activity Score (DAS28), disease duration, and anti-TNF, methotrexate, and prednisolone use.Results.At initiation of anti-TNF therapy (baseline), 328 women and 148 men had early RA (≤ 2 yrs), and 1245 women and 408 men had established RA (> 2 yrs). In both early and established RA, men and women had active disease with similar DAS28 scores (mean ± SD 5.2 ± 1.1), physician global scores, swollen joint counts, and radiographic changes. In early RA, men were significantly more likely to achieve a EULAR good/moderate response over 48 months compared to women (GEE; p = 0.003), and a significant interaction between sex and followup time (GEE; p < 0.0005) suggested that men achieved this response sooner than women.Conclusion.Better responses to anti-TNF therapy among men compared to women in early but not established RA suggest that disease duration at initiation of therapy may be an important factor to consider when investigating sex differences in treatment responses.

Objective.To investigate by magnetic resonance imaging (MRI) which bones in wrists and metacarpophalangeal (MCP) joints most frequently show bone erosions, and which most frequently demonstrate erosive progression, in early and established rheumatoid arthritis (RA).Methods.MRI datasets from 258 RA patients [126 with early RA (disease duration < 6 months)] were analyzed, of whom 223, including 126 with early RA, had 1-year followup MRI. All patients had MRI of one wrist, whereas 86 patients had additional images of 2nd–5th MCP joints, and 46 patients additional images of the contralateral wrist. MRI were evaluated blinded by one reader, according to the OMERACT RA MRI scoring system (RAMRIS) for erosions, and presence/absence of erosions was noted in each bone, as was presence/absence of erosive progression.Results.The capitate, ulna, lunate, triquetrum, and scaphoid were the 5 bones with both most frequent baseline erosions and most frequently demonstrated erosive progression. No bones were without erosions. Patterns of erosions and progression were similar in early and established RA. No major difference between dominant and nondominant wrists was detected. In the fingers, the 2nd–3rd MCP joint most frequently displayed erosions and erosive progression.Conclusion.The distribution and frequency of bone erosion and erosive progression as detected by MRI in RA wrists and MCP joints were identified. No pattern differences between early versus established disease and dominant versus nondominant sides were detected. No bones showed erosive progression. Thus, no self-evident simplification of the RAMRIS erosion score was identified. Bone involvement patterns may be considered, when joints are selected for MRI protocols for clinical trials and practice.

Objective.In rheumatoid arthritis (RA), radiographic progression may occur despite clinical remission. This may be explained by subclinical inflammation. Magnetic resonance imaging (MRI) provides a greater sensitivity than clinical examination and radiography for assessing disease activity. Our objective was to determine the MRI characteristics of RA patients in clinical remission or low disease activity (LDA) state.Methods.Databases from 6 cohorts were collected from 5 international centers. RA patients in clinical remission according to Disease Activity Score28-C-reactive protein (DAS28-CRP < 2.6; n = 213) or LDA-state (2.6 ≤ DAS28-CRP < 3.2; n = 81) with available MRI data were included. MRI were assessed according to the OMERACT RA MRI scoring system (RAMRIS).Results.Patient characteristics: 70% women, median age 55 (interquartile range, IQR 43–63) years, disease duration 2.3 (IQR 0.7–5.1) years, DAS28-CRP 2.2 (IQR 1.8–2.6), Simplified Disease Activity Index, SDAI, 3.9 (IQR 1.9–6.5), Clinical Disease Activity Index, CDAI, 3.1 (IQR 1.5– 5.8), rheumatoid factor/anti-cyclic citrullinated peptide positivity 57%/54%, presence of radiographic erosions: 66%. Wrist and metacarpophalangeal MRI (MCP-MRI) data were available for 287 and 241 patients, respectively. MRI inflammatory activity in wrist and/or MCP joints was observed in the majority [synovitis: 95%, bone edema (osteitis): 35%] of patients. The median (IQR) RAMRIS score was 6 (3–9) for synovitis and 0 (0–2) for osteitis. Synovitis and osteitis were not less frequent in DAS28 clinical remission (synovitis/osteitis 96%/35%) than LDA (91/36). A trend towards lower frequencies of osteitis in patients in SDAI and CDAI remission was observed.Conclusion.Subclinical inflammation was identified by MRI in the majority of RA patients in clinical remission or LDA state. This may explain structural progression in such patients. Further work is required to understand the place of modern imaging in future remission criteria.

Objective. To compare health-related quality of life (HRQOL) of patients with rheumatoid arthritis (RA) to that of the general population and to investigate the association with disease activity, focusing on different clinical remission criteria.Methods. EQ-5D data from 3156 patients with RA from 11 Danish centers were compared with Danish EQ-5D population norms (n = 16,136). The Disease Activity Score (DAS28) and the Clinical Disease Activity Index score (CDAI) were used as definitions of disease activity and clinical remission. The score difference (ΔEQ-5D) was calculated in each patient as the difference from the age and sex-matched general population and adjusted for age, marital status, education, body mass index, smoking, exercise habits, disease duration, IgM-rheumatoid factor status, joint surgery, extraarticular features, treatment, and comorbidity in multiple linear regression models.Results. 37% vs 22% fulfilled the DAS28 and CDAI remission criteria, respectively. The ΔEQ-5D values for women/men in clinical remission were DAS28 0.05/0.06 vs CDAI 0.01/0.02; low disease activity: DAS28 0.12/0.13 vs CDAI 0.11/0.14; moderate disease activity: DAS28 0.18/0.20 vs CDAI 0.20/0.23; and high disease activity: DAS28 0.38/0.28 vs CDAI 0.33/0.26. Adjusting for confounders reduced the ΔEQ-5D values between 0 and 0.04 units.Conclusion. Patients with RA had worse EQ-5D scores than the general population, and the difference was strongly associated with disease activity. The EQ-5D score for patients in clinical remission approached that of the general population, suggesting that strict treatment goals are critical in order to achieve near-normal HRQOL in patients with RA.

Objective.To study the association between polymorphisms in the mannose-binding lectin gene (MBL2)and disease activity, physical disability, and joint erosions in patients with newly diagnosed rheumatoid arthritis (RA).Methods.Patients with early RA (n = 158) not previously treated with disease modifying antirheumatic drugs, participating in a treatment trial (CIMESTRA study) were examined at inclusion forMBL2pooled structural genotypes (O/O, A/O, A/A), regulatoryMBL2promoter polymorphism in position −221 (XX, XY, YY), anti-cyclic citrullinated peptide 2 antibodies (anti-CCP2), disease activity by Disease Activity Score-28 (DAS28 score), physical disability by Health Assessment Questionnaire (HAQ) score, and erosive changes in hands and feet (Sharp-van der Heijde score).Results.Eight patients were homozygousMBL2defective (O/O), 101 belonged to an intermediate group, and 49 wereMBL2high producers (YA/YA). Anti-CCP was present in 93 patients (59%). High scores of disease activity, C-reactive protein-based DAS28 (p = 0.02), and physical disability by HAQ (p = 0.01) were associated with highMBL2expression genotypes in a gene-dose dependent way, but only in anti-CCP-positive patients. At this early stage of the disease there was no association with erosion score from radiographs.Conclusion.The results point to a synovitis-enhancing effect of MBL in anti-CCP-positive RA, whereas such an effect was not demonstrated for joint erosions.