Occurrence and Prediction of Flare After Tapering of Tumor Necrosis Factor Inhibitors in Patients With Axial Spondyloarthritis.

OBJECTIVE: Patients with axial spondyloarthritis (axSpA) in clinical remission tapered tumor necrosis factor inhibitor (TNFi) therapy according to a clinical guideline. Over a 2-year follow-up period, we aimed to investigate flare frequency, dose at which flare occurred, type of flare, and predictors thereof. METHODS: Patients in clinical remission (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] < 40, physician global score < 40, and without disease activity the previous year) tapered TNFi to two-thirds the standard dose at baseline, half at week 16, one-third at week 32, and discontinued at week 48. Flares were defined as BASDAI flare (BASDAI ≥ 40 and change ≥ 20 since inclusion), and/or clinical flare (development of inflammatory back pain, musculoskeletal or extraarticular manifestations, and/or Ankylosing Spondylitis Disease Activity Score [ASDAS] ≥ 0.9), and/or magnetic resonance imaging (MRI) flare (≥ 2 new or worsened inflammatory lesions). RESULTS: Of 108 patients, 106 (99%) flared before 2-year follow-up: 29 patients (27%) at two-thirds standard dose, 21 (20%) at half dose, 29 (27%) at one-third dose, and 27 (25%) after discontinuation. Regarding type of flare, 105 (99%) had clinical flares, 25 (24%) had BASDAI flares, and 23 (29% of patients with MRI at flare available) had MRI flares. Forty-one patients (41%) fulfilled the Assessment of SpondyloArthritis international Society (ASAS) definition of clinically important worsening (≥ 0.9 increase since baseline). Higher baseline physician global score was an independent predictor of flare after tapering to two-thirds (OR 1.19, 95% CI 1.04-1.41, P = 0.01). Changes in clinical and/or imaging variables in the 16 weeks prior to tapering did not predict flare. CONCLUSION: Almost all (99%) patients with axSpA in clinical remission experienced flare during tapering to discontinuation, but in over half of these patients, flare did not occur before receiving one-third dose or less. Higher physician global score was an independent predictor of flare.

Tapering of TNF inhibitors in axial spondyloarthritis in routine care - 2-year clinical and MRI outcomes and predictors of successful tapering.

OBJECTIVES: In a 2-year follow-up study of patients with axial spondyloarthritis (axSpA) in clinical remission who tapered TNF inhibitor (TNFi) treatment according to a clinical guideline, we aimed to investigate the proportion who successfully tapered/discontinued therapy and baseline predictors thereof. The proportion regaining clinical remission after flare and the progression on MRI/radiography were also assessed. METHODS: One-hundred-and-nine patients (78 [72%]/31 [28%] receiving standard and reduced dose, respectively) in clinical remission (BASDAI < 40, physician global score < 40) and no signs of disease activity the previous year tapered TNFi as follows: to two-thirds of standard dose at baseline, half at week 16, one-third at week 32 and discontinuation at week 48. Patients experiencing clinical, BASDAI or MRI flare (predefined criteria) stopped tapering and escalated to previous dose. Prediction analyses were performed by multivariable regression. RESULTS: One hundred and six patients (97%) completed 2 years' follow-up; 55 patients (52%) had successfully tapered: 23 (22%) receiving two-thirds, 15 (14%) half, 16 (15%) one-third dose and 1 (1%) discontinued. In patients at standard dose at baseline (n = 78), lower physician global score was the only independent predictor of successful tapering (odds ratio [OR] = 0.79 [95% CI: 0.64, 0.93]; P = 0.003). In the entire patient group lower physician global score (OR = 0.86 [0.75, 0.98]; P = 0.017), lower Spondyloarthritis Research Consortium of Canada (SPARCC) Sacroiliac Joint Erosion score (OR = 0.78 [0.57, 0.98]; P = 0.029) and current smoker (OR = 3.28 [1.15, 10.57]; P = 0.026) were independent predictors of successful tapering. At 2 years, 97% of patients were in clinical remission. Minimal changes in imaging findings were observed. CONCLUSION: After 2 years following a clinical guideline, 52% of patients with axSpA in clinical remission had successfully tapered TNFi, only 1% discontinued. Baseline physician global score was an independent predictor of successful tapering.

Musculoskeletal pain in psoriasis-relation to inflammation and additional value of ultrasound in psoriatic arthritis classification.

OBJECTIVE: To investigate and compare clinical features and US signs of inflammation in joints and entheses in patients with psoriasis with and without musculoskeletal pain, and the additional value of US in classification of PsA. Furthermore, to explore the association between such findings and patient-reported outcomes (PROs) and the performance of screening-questionnaires for identifying patients with PsA. METHODS: Patients with psoriasis (n = 126) recruited from a nationwide survey were evaluated at one of four rheumatology departments. The evaluation included clinical examination, laboratory tests, radiography, greyscale and colour Doppler US of 48 joints and 12 entheses, PROs, and four screening questionnaires for PsA. Patients were classified with Classification for PsA (CASPAR), US-modified CASPAR, and US-only criteria. RESULTS: When subgroups of self-reported pain (63%), no pain (29%) and diagnosed PsA (9%) were compared, patients with pain had higher tenderness-related clinical scores (tender joints, entheses and FM points) and US greyscale sum-scores, compared with 'no pain' patients. PROs were negligibly moderately correlated with pain-related clinical scores (Spearman's rho = 0.11-0.59, all patients), and negligibly weakly with US sum-scores (rho = 0.01-0.34). More patients could be classified as PsA when US synovitis/enthesitis was included as an entry criterion (US-modified CASPAR, 66% of all patients) compared with conventional CASPAR (35%) or US-only criteria (52%). Sensitivities of screening questionnaires were low for fulfilment of CASPAR (0.23-0.66), US-modified CASPAR (0.17-0.57), and US-only (0.20-0.57) criteria. CONCLUSION: Self-reported pain in psoriasis is related to US inflammation. US-modified CASPAR criteria identified almost twice as many patients as conventional CASPAR criteria. Screening questionnaires showed limited value.

Increased galectin-3 may serve as a serologic signature of pre-rheumatoid arthritis while markers of synovitis and cartilage do not differ between early undifferentiated arthritis subsets.

BACKGROUND: Undifferentiated arthritis (UA) is a label applied to patients with joint complaints which cannot be classified according to current criteria, which implies a need for precision diagnostic technologies. We studied serum galectin-3, a proinflammatory mediator, and seromarkers of structural joint elements in patients with early, UA and their associations with disease profile and biochemical and imaging findings. METHODS: One hundred and eleven UA patients were followed-up for at least 12 months and reclassified according to appropriate criteria (TUDAR). At baseline, demographics and laboratory and clinical disease measures, as well as wrist magnetic resonance imaging (MRI) synovitis, erosion, and bone marrow edema scorings, were recorded. Galectin-3, the type IIA collagen N-terminal propeptide (PIIANP), which is a marker of regenerative cartilage formation, and hyaluronan (HYA), which is prevalent in synovial tissue swellings, were measured by enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristic (ROC) curve analysis was carried out to assess the discriminant capacity of galectin-3 against arthritis subsets. RESULTS: Galectin-3 was increased in pre-rheumatoid arthritis (RA) (4.6 µg/l, interquartile range (IQR) 3.8-5.5) versus non-RA (4.0 µg/l, IQR 3.1-4.9; p = 0.03) and controls (3.8 µg/l, IQR 3.0-4.8; p = 0.009). PIIANP was equally depressed in either subset (p < 0.01). Galectin-3 in non-RA and HYA in UA did not differ from healthy controls. In the entire UA cohort, galectin-3 correlated with the MRI bone marrow edema score, while PIIANP correlated with the MRI erosion score, and HYA with the synovitis and erosion scores. ROC curve analysis showed that baseline galectin-3 discriminated well between pre-RA and non-RA with univariate area under the curve (AUC) of 0.64 (95% confidence interval (CI) 0.53-0.76) while AUC for galectin-3 + anti-CCP increased to 0.71 (95% CI 0.59-0.83). CONCLUSIONS: Galectin-3 in serum was increased in patients with early UA of pre-RA origin. Cartilage remodeling assessed by PIIANP was diminished in UA irrespective of subsequent clinical differentiation, while HYA did not differ from controls. ROC analysis showed a potential for galectin-3 to discriminate between pre-RA and non-RA. TRIAL REGISTRATION: KF 11 315829. Registered 25 July 2006.

Can magnetic resonance imaging differentiate undifferentiated arthritis?

A high sensitivity for the detection of inflammatory and destructive changes in inflammatory joint diseases makes magnetic resonance imaging potentially useful for assigning specific diagnoses, such as rheumatoid arthritis and psoriatic arthritis in arthritides, that remain undifferentiated after conventional clinical, biochemical and radiographic examinations. With recent data as the starting point, the present paper describes the current knowledge on magnetic resonance imaging in the differential diagnosis of undifferentiated arthritis.

Magnetic resonance imaging of peripheral joints in rheumatic diseases.

The need for better methods than the conventional clinical, biochemical and radiographical examinations in the management of inflammatory joint diseases is evident, since these methods are not sensitive or specific to early pathologies and subtle changes. Magnetic resonance imaging (MRI) offers improved sensitivity to early inflammatory and destructive changes in peripheral joints in rheumatoid arthritis (RA) and, even though less well documented, in other inflammatory joint diseases. Good evidence is available that MRI bone erosions represent true bone abnormalities and are predictors of radiographical outcome in RA. Similarly, there is solid evidence for MRI synovitis representing true synovial inflammation and being of considerable practical, clinical and radiological significance in RA. Describing the encouraging current knowledge regarding MRI for diagnosis, monitoring and prognosis, this chapter discusses the potential for the use of MRI in the clinical management of patients with suspected and diagnosed inflammatory joint diseases, as well as research priorities and clinical situations where the use of MRI could be suggested.