Characteristics of difficult-to-treat axial spondyloarthritis: Results of a real-world multicentric study.

OBJECTIVE: The EULAR task force recently published the difficult-to-treat RA (D2T RA) definition, however, a definition of D2T axSpA is still lacking and limitations in this definition exist. The objectives were to study the characteristics of D2T axSpA patients using the EULAR definition and to study a subgroup of patients with a predefined more stringent definition including a temporal criterion. METHODS: A multicentric retrospective study was performed. D2T axSpA was defined as failure of≥2 b/tsDMARDs with different mechanism of action. Very D2T axSpA was defined as failure of≥2 b/tsDMARDs in less than 2 years of follow-up. D2T and Very D2T axSpA patients were compared to non-D2T (nD2T) axSpA patients. RESULTS: Three hundred and eleven axSpA patients were included: 88 D2T axSpA (28.3%) and 223 non-D2T (nD2T) axSpA (71.7%). Peripheral involvement was more prevalent in the D2T group (34.9 vs. 21.4%; P=0.015). BASDAI level at baseline was higher in the D2T group (63.7±16.5 vs. 58.8±14.7; P=0.015). Fibromyalgia was found to be more frequent in the D2T group vs nD2T group (P<0.001). Twelve patients (3.8%) were categorized as very D2T axSpA. Compared to nD2T, Very D2T patients had a higher CRP level at baseline (42.0±31.3 vs. 17.8±23.1; P=0.010). IBD prevalence at baseline was higher in the very D2T group (41.7 vs. 3.1%; P<0.001). None of the very D2T patients presented a fibromyalgia. CONCLUSION: D2T axSpA was associated with higher disease activity, peripheral involvement, extra-musculoskeletal manifestations and fibromyalgia. Very D2T patients represented a minim proportion of patients after applying a more stringent definition including a temporal criterion of 2 years and might be independent from fibromyalgia.

Characteristics Of Difficult-To-Treat Psoriatic Arthritis: A Comparative Analysis.

OBJECTIVE: The EULAR task force recently published the difficult-to-treat rheumatoid arthritis (D2T RA) criteria, however, a definition of D2T patients in psoriatic arthritis (PsA) is still lacking. To date, we have little data concerning D2T PsA, especially in real-world. One of the limitations of the D2T RA EULAR definition is the absence of a temporal criterion. The primary endpoint of this work was to study the characteristics of D2T PsA patients using the EULAR definition. The second objective was to study a sub-group of patients with a predefined more stringent definition including a temporal criterion. METHODS: A retrospective study was performed in a tertiary center. D2T PsA was defined as failure of ≥ 2 b/tsDMARDs with different mechanism of action. Very D2T PsA was defined as failure of ≥ 2 b/tsDMARDs in less than 2 years of follow-up. D2T and Very D2T PsA patients were compared to nD2T PsA patients using statistical tests. RESULTS: 150 PsA patients were included (from 2004 to 2015): 49 D2T PsA and 101 nD2T PsA. D2T PsA was associated with a higher prevalence of axial involvement (p=0.030), axial and/or peripheral structural damage (p=0.007) at baseline and more bDMARDs discontinuation due to poor dermatological control (p=0.005). There was no significant difference regarding comorbidities such as obesity, smoking status, fibromyalgia or depression. In multivariate analysis, peripheral structural damage at baseline was found to be a predictive factor for D2T PsA with an OR of 2.57 (1.16 to 5.69; p=0.020). 17 PsA (11.3%) patients were categorized as Very D2T PsA. When compared to nD2T group, proportion of obesity was higher (p=0.015) and axial involvement was more prevalent in the Very D2T group (p=0.020). CONCLUSION: D2T PsA patients had a higher prevalence of axial involvement, peripheral structural damage and therapeutic discontinuation due to poor dermatological control whereas Very D2T PsA patients were more likely obese with axial involvement. Very D2T PsA represent a minim proportion among patients when applying a more stringent definition. Pending the PsA D2T definition by the European and American societies, this study highlights some characteristics that may help practitioners better identify D2T patients.

Efficacy and management of tocilizumab in polymyalgia rheumatica: results of a multicenter retrospective observational study.

OBJECTIVES: The efficacy of anti-IL6 receptors such as Tocilizumab (TCZ) was demonstrated in patients with Polymyalgia Rheumatica (PMR) in two recent randomized controlled trials. The objective of this multicentre retrospective study was to assess the efficacy of TCZ in PMR patients requiring GC-sparing treatment, as well as different strategies for TCZ withdrawal. METHODS: We conducted a multicentre study in French tertiary health care departments for patients with PMR. PMR patients receiving off-label TCZ between 2015 and 2022 were included. The primary end point was the proportion of patients tapering to glucocorticoids (GCs) ≤5mg/day 6 months after the first TCZ infusion. The secondary endpoints were the proportion in whom GC was discontinued during follow-up, and the proportion of patients in whom TCZ was discontinued. RESULTS: Fifty-three PMR patients were included. Thirty-one (31) patients suffered from active PMR despite csDMARDs. GCs were ≤5mg/day in 77% of the patients (95% confidence interval [CI95%]: 36-89) at 6 months, and in 97% of the patients at 12 months. Six and 12 months after the first TCZ infusion, the proportions of GC-free patients were 22.5% (CI95%: 12.7-37.8) and 58.3% (CI95%: 43.2-74.1), respectively. Among TCZ withdrawal strategies, TCZ infusion spacing and TCZ dose reduction were more successful (success in 87% and 79% of attempts, respectively) than TCZ discontinuation (success in 52% of attempts; p= 0.012 and p= 0.039, respectively). CONCLUSION: In GC-dependent PMR patients, treatment with TCZ led to a drastic decrease in GC dose and remission of PMR. TCZ dose reduction or TCZ infusion spacing are good options to consider in TCZ withdrawal.

Characteristics of Patients Treated with JAK Inhibitors in Rheumatoid Arthritis before versus after VTE Risk Warnings.

BACKGROUND: Baricitinib (BARI) or Tofacitinib (TOFA) were the first Janus Kinase Inhibitors (JAKi) to be marketed in rheumatoid arthritis (RA). Concerns regarding venous thromboembolism (VTE) risk have emerged during the past years. The aim of the study was to compare the baseline characteristics of patients initiating BARI or TOFA in RA before versus after European Medicine Agency (EMA)'s VTE warnings and to compare real-world persistence with these two drugs. METHODS: In this multicentric cohort study, RA patients initiating BARI or TOFA were included from October 2017, date of BARI marketing authorization in France, to September 2020. Baseline characteristics regarding VTE risk were compared (before vs. after May 2019) by using pre-specified statistical tests. Comparison of persistence was assessed by using propensity-score methods. RESULTS: 232 patients were included; 155 with BARI and 77 with TOFA. Baseline characteristics of patients regarding VTE risk factors were not statistically different when Janus Kinase inhibitor (JAKi) was initiated before vs. after EMA's warnings although a trend towards a lower proportion of VTE history was observed. Five VTE events occurred, four with BARI, one with TOFA. Cumulative persistence rate at 2 years was similar between BARI and TOFA: HR 0.96; 95% Cl: 0.52 to 1.74; p = 0.89. CONCLUSIONS: Our study did not show a significant change in patients characteristics starting a JAKi after the EMA's warnings, probably due to a lack of power. Though, the lower proportion of VTE history in patients after May 2019 suggests that rheumatologists have taken into account the potential VTE risk. These results need to be confirmed by further evidence.

Lymphoma complicating rheumatoid arthritis: results from a French case-control study.

OBJECTIVES: To study the characteristics of B-cell non-Hodgkin's lymphoma (NHL) or Hodgkin lymphoma complicating rheumatoid arthritis (RA) and to identify RA-related factors associated with their occurrence. METHODS: A multicentre case-control study was performed in France. Cases were patients with RA fulfilling ACR-EULAR 2010 criteria in whom B-cell NHL or Hodgkin lymphoma developed after the diagnosis of RA. For each case, 2 controls were assigned at random from the ESPOIR cohort and were matched on age at lymphoma diagnosis (cases)/age at the 10-year follow-up visit in the cohort (controls). Case and control characteristics were compared to identify parameters associated with the occurrence of lymphoma. RESULTS: 54 cases were included and matched to 108 controls. Lymphomas were mostly diffuse large B-cell lymphoma (DLBCL, n=27, 50.0%). On immunochemistry, 4 of 27 (14.8%) lymphoma cases were positive for Epstein-Barr virus. On univariate analysis, factors associated with the occurrence of lymphoma were male sex (OR 3.3, 95% CI 1.7 to 6.7), positivity for ACPA (OR 5.1, 95% CI 2.0 to 15.7) and rheumatoid factor (OR 3.9, 95% CI 1.6 to 12.2), and erosions on radiographs (OR 3.8, 95% CI 1.7 to 8.3) and DAS28 (OR 2.0, 95% CI 1.5 to 2.7), both at the time of matching. Methotrexate, TNF blockers and a number of previous biologics were not associated with the occurrence of lymphoma. On multivariable analysis, erosions and DAS28 remained significantly associated with increased risk of lymphoma. CONCLUSION: Lymphomas complicating RA are mostly DLBCL. Risk of lymphoma in patients with RA was increased with markers of disease activity and severity, which supports the paradigm of a continuum between autoimmunity and lymphomagenesis in RA.

Secukinumab and ustekinumab treatment in psoriatic arthritis: results of a direct comparison.

OBJECTIVES: To evaluate the characteristics of patients (pts) with PsA treated by ustekinumab (UST) or secukinumab (SEK) and to compare real-world persistence of UST and SEK in PsA. METHODS: In this retrospective, national, multicentre cohort study, pts with PsA (CASPAR criteria or diagnosis confirmed by the rheumatologist) initiating UST or SEK with a follow-up ≥6 months were included from January 2011 to April 2019. The persistence between SEK and UST was assessed after considering the potential confounding factors by using pre-specified propensity-score methods. Causes of discontinuation and tolerance were also collected. RESULTS: A total of 406 pts were included: 245 with UST and 161 with SEK. The persistence rate was lower in the UST group compared with the SEK group [median persistence 9.4 vs 14.7 months; 26.4% vs 38.0% at 2 years; weighted hazard ratio (HR) = 1.42; 95% CI: 1.07, 1.92; P =0.015]. In subgroup analysis, the persistence rate of SEK associated with MTX was significantly higher than that of UST associated with MTX: HR = 2.20; 95% CI: 1.30, 3.51; P =0.001, in contrast to SEK vs UST monotherapy: HR = 1.06; 95% CI: 0.74, 1.53; P =0.75. Discontinuation due to inefficacy was reported in 91.7% (SEK) and 82.4% (UST) of pts. Discontinuation due to an adverse event was reported in 12.2% (SEK) and 7.7% (UST) of pts. CONCLUSION: In this first study comparing UST and SEK, the persistence of SEK was higher than that of UST in PsA. In subgroup analysis, this difference was only found in association with MTX.

Association Between Comorbidities and Quality of Life in Psoriatic Arthritis: Results from a Multicentric Cross-sectional Study.

OBJECTIVE: In psoriatic arthritis (PsA), comorbidities add to the burden of disease, which may lead to poorer quality of life. The purpose of this study was to evaluate the relationship between comorbidities and quality of life (QOL). METHODS: Patients from a multicentric, cross-sectional study on comorbidities in PsA were included in the analysis. Data on comorbidities were collected and were subsequently used to compute the modified Rheumatic Disease Comorbidity Index (mRDCI). The Medical Outcomes Study Short Form-36 questionnaire physical (PCS) and mental component summary (MCS) scales were used to assess QOL. RESULTS: In total, 124 recruited patients fulfilled the ClASsification for Psoriatic ARthritis criteria (CASPAR): 62.1% were male; mean age and mean disease duration were 52.6 ± 12.6 years and 11.3 ± 9.6 years, respectively. The number of comorbid conditions was 2.0 ± 1.3, with 30.6% of the sample having currently or a history of 3 or more comorbidities. In the multivariate linear regression analysis, only anxiety remained significantly related to mental health (p < 0.0001). Anxiety alone accounted for 28.7% of the variance in MCS scores. Moreover, MCS was also significantly associated with the mRDCI score, which explained 4.9% of the variance in MCS [ß = -1.56 (standard error 0.64), R2 = 0.049, p = 0.0167]. In contrast, PCS was not significantly associated either with type or number of comorbidities. CONCLUSION: In this study, the type of comorbidity appeared to have a greater effect than the number of comorbidities. Indeed, anxiety in PsA was independently associated with QOL and would thus be an important factor to take into account in daily clinical practice.

Abatacept Monotherapy Versus Abatacept Plus Methotrexate for Treatment-Refractory Rheumatoid Arthritis.

BACKGROUND: Methotrexate combination therapy improves abatacept efficacy as a first-line biologic agent for the treatment of rheumatoid arthritis, but it is unclear when abatacept is used later on, particularly after non-TNF inhibitor (TNFi) failure. STUDY QUESTION: The objective of this study was to determine whether treatment response after non-TNFi inadequate response is different in patients with rheumatoid arthritis (RA) treated with abatacept in combination with or not with methotrexate. METHODS: Patients treated with abatacept monotherapy or in combination with methotrexate after non-TNFi failure were included. RESULTS: Data from 46 patients aged 56 years [49-61] with 12 years [8-16] of disease duration were examined. Rituximab was the treatment used in the previous line for 75.0% of the combination therapy group (15/20) and 34.6% (9/26) in the monotherapy group. At 12 months, 38.5% (10/26) of patients were in good-to-moderate EULAR response in the monotherapy group compared with 25.0% (5/20) in the combination therapy group (P = 0.33). Treatment persistence at 12 months was 61.5% (16/26) in the monotherapy group and 35.0% (7/20) in the combination therapy group (P = 0.07). CONCLUSIONS: Adding methotrexate to abatacept did not improve treatment response in patients with RA after non-TNFi inadequate response.

Takayasu Arteritis and Spondyloarthritis: Coincidence or Association? A Study of 14 Cases.

OBJECTIVE: Spondyloarthritis (SpA) and Takayasu arteritis (TA) are 2 chronic inflammatory diseases; their coexistence in a single patient is uncommon. The aims of our study were to describe clinical features of patients having SpA associated with TA and to identify some characteristics of the types of patients with SpA associated with TA. We also analyzed treatments used in this context. METHODS: This French multicenter retrospective survey called for observations on behalf of the Club Rhumatismes et Inflammations, with a standardized questionnaire established by the investigators. RESULTS: We included 14 patients (women: 10/14; median age at SpA diagnosis: 43.5 yrs, ranging from 19 to 63). Subtypes of SpA were ankylosing spondylitis (n = 11), psoriatic arthritis (n = 2), and synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome (n = 1). HLA-B27 was positive in 3 cases, negative in 9, and unknown in 2. SpA was diagnosed before TA in 13 cases. Imaging findings compatible with the diagnosis of TA were found with computed tomography (11/14) and/or Doppler ultrasound (10/14). Laboratory tests showed increased acute-phase reactants in all cases (C-reactive protein ≥ 25 mg/l in 71% of the cases). All patients except 1 received corticosteroids and 7 were treated with anti-tumor necrosis factor (anti-TNF). CONCLUSION: Association of SpA and TA is rare but probably not coincidental. Peripheral pulse palpation and vascular auscultation should be systematic and are the first indicators of TA in patients with SpA. Moreover, increased acute-phase reactants during SpA followup should lead to search for TA. Finally, there are therapeutic implications because anti-TNF are efficient in SpA and might be efficient in TA.

Are abatacept and tocilizumab intravenous users willing to switch for the subcutaneous route of administration? A questionnaire-based study.

Choosing the subcutaneous (SC) route of administration of abatacept and tocilizumab is more cost-effective than the intravenous (IV) route. The objective of this study was to examine patients' reasons for choosing to keep with their IV infusions or to switch to subcutaneous SC injections. This study was based upon a self-administered questionnaire given to consecutive rheumatoid arthritis patients treated with abatacept or tocilizumab. Patients were asked to express their opinions concerning reasons explaining why they chose to keep the IV route or switch to the SC route. A total of 201 questionnaires completed by 127 patients treated by tocilizumab and 74 by abatacept were analysed. Overall, 45.8% of the patients chose to keep the IV route of administration. Another ongoing SC treatment was noted more often in patients choosing the SC route (15.9 versus 4.3%, p < 0.05). Reasons guiding the choice of the SC route were concerns about repeated hospital day-care (72%), greater autonomy with SC injections (38.7%) and economic considerations (21.5%). Reasons associated with choosing to maintain the IV route were worries about a lack of follow-up (72.1%), the absence of medical assistance during the SC injection (61.2%), maintaining social relationships with other patients developed at the hospital (40.5%), lower frequency of injection (32.9%), fear of adverse events (27.7%) and fear of SC injections (17.9%). Patients reject the SC switch from the IV route of tocilizumab and abatacept mainly because of fears about the unknown SC route, while those who accept it find it more convenient.

Soluble vascular endothelial (VE) cadherin and autoantibodies to VE-cadherin in rheumatoid arthritis patients treated with etanercept or adalimumab.

OBJECTIVES: The aim of this study was to investigate the clinical value of sVE and anti-vascular endothelial-cadherin antibodies (AAVE) in RA treated with etanercept or adalimumab combined with methotrexate. METHODS: This was an 18-month prospective multicenter study in which patients had active RA, requiring TNF antagonist. sVE rates and AAVE titers were measured respectively by dot blot and ELISA. The relationship of these biomarkers with parameters reflecting articular or systemic disease activity, progression of structural damage, and response or remission to treatment was analyzed. RESULTS: Forty-eight patients received TNF blocking agents. Variation of sVE rates were significantly correlated with that of C-reactive protein (CRP) levels at weeks 6, 12, 26 and 52. A significant decrease in sVE levels was observed in the group of patients exhibiting a decrease in CRP levels as compared to the patient group with unmodified CRP. AAVE at baseline were correlated with rheumatoid factor. Kinetics analysis of sVE levels and AAVE titers showed that their level were not associated with disease activity score and to methotrexate/adalimumab or etanercept response. CONCLUSIONS: sVE is a biomarker associated with systemic RA activity under anti-TNF. AAVE are related to autoantibodies usually associated to RA.

Comparative efficacy of tocilizumab, abatacept and rituximab after non-TNF inhibitor failure: results from a multicentre study.

AIMS: The aim of this study was to compare the efficacy of tocilizumab, rituximab and abatacept after a non-tumor necrosis factor inhibitor (non-TNFi) failure for the treatment of rheumatoid arthritis (RA). MATERIALS AND METHODS: This retrospective multi-centre study included patients treated for RA with abatacept, rituximab or tocilizumab after having received in the previous line the first non-TNFi. Data were collected from patient charts. The primary endpoint was the delta Disease Activity Index of 28 joints - erythrocyte sedimentation rate (DAS28-ESR) and DAS28-CRP (C-reactive protein) at 12 months. The relative change in primary outcome measures from baseline were calculated. RESULTS: One hundred patients started a second non-TNFi between 2006 and 2013, including 15 patients treated with rituximab, 36 with tocilizumab and 49 with abatacept. The change of DAS28-ESR was significantly different between the three groups (P = 0.001). In post hoc pairwise comparisons, patients treated with tocilizumab had a higher decrease of the DAS28-ESR than patients treated by abatacept (median [interquartile range: IQR]: 36% [0; 54%] vs. 0% [0; 20%], P = 0.002). A similar non-significant difference was found between tocilizumab and rituximab (median [IQR] decrease: 36% [0; 54%] vs. 0% [-11; 34%], P = 0.07). Similar results were found with the 12 months change in DAS28-CRP. CONCLUSIONS: This study suggests a better efficacy of tocilizumab compared with abatacept and rituximab in situations of non-TNFi failure.

Tumor Necrosis Factor-α Inhibition in Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis: Treatment Response, Drug Survival, and Patient Outcome.

OBJECTIVE: The purpose of this study was to (1) evaluate baseline characteristics of nonradiographic axial spondyloarthritis (nr-axSpA) and ankylosing spondylitis (AS) treated with tumor necrosis factor-α inhibitors (TNFi), (2) assess the response to first TNFi treatment, and (3) compare drug-survival duration and rates. METHODS: Inclusion criteria were patients with axSpA who initiated first TNFi treatment between April 2001 and July 2014 and were followed up for at least 3 months. Efficacy criteria were an improvement of at least 2 points (on a 0-10 scale) or a 50% improvement in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Baseline characteristics, responses at 12 months, and drug survival were compared between AS and nr-axSpA. RESULTS: A total of 361 patients were included in the study (AS, n = 263 and nr-axSpA, n = 98). Patients with AS were more often men (65.02% vs 45.92%, p = 0.001) and had longer symptom duration (11.71 ± 9.52 vs 7.34 ± 9.30 yrs, p < 0.001). Median levels of acute-phase reactants (C-reactive protein and erythrocyte sedimentation rate) were significantly higher in patients with AS (p < 0.001 for both). Median BASDAI scores at first TNFi initiation were not higher in patients with nr-axSpA than in patients with AS (59, 49-70 vs 60, 50-70, p = 0.73). BASDAI 20 and BASDAI 50 response rates at 12 months were not statistically different between patients with AS and patients with nr-axSpA (74.58% vs 64.58%, p = 0.19 and 61.02% vs 50.00%, p = 0.19, respectively). No statistically significant difference in terms of survival was observed between patients with AS and nr-axSpA (p = 1.00). CONCLUSION: Treatment response and drug survival were similar in patients with AS and nr-axSpA after first TNFi initiation.

Identification of 7 Proteins in Sera of RA Patients with Potential to Predict ETA/MTX Treatment Response.

OBJECTIVE: The recent growth of innovating biologics has opened fascinating avenues for the management of patients. In rheumatoid arthritis, many biologics are currently available, the choice of which being mostly determined empirically. Importantly, a given biologic may not be active in a fraction of patients and may even provoke side effects. Here, we conducted a comparative proteomics study in attempt to identify a predictive theranostic signature of non-response in patients with rheumatoid arthritis treated by etanercept/methotrexate combination. METHODS: A serum sample was collected prior to treatment exposure from a cohort of 22 patients with active RA. A proteomic "label free" approach was then designed to quantitate protein biomarkers using mass spectrometry. To verify these results, a relative quantification followed by an absolute quantification of interesting protein candidates were performed on a second cohort. The criterion of judgment was the response to etanercept/methotrexate combination according to the EULAR criteria assessed at 6 months of treatment. RESULTS: These investigations led to the identification of a set of 12 biomarkers with capacity to predict treatment response. A targeted quantitative analysis allowed to confirm the potential of 7 proteins from the latter combination on a new cohort of 16 patients. Two highly discriminating proteins, PROS and CO7, were further evaluated by ELISA on this second cohort. By combining the concentration threshold of each protein associated to a right classification (responders vs non-responders), the sensitivity and specificity reached 88.9 % and 100 %, respectively. CONCLUSION: Prior to methotrexate/etanercept treatment, abundance of several sera proteins, notably PROS and CO7, were associated to response status of RA patients 6 month after treatment initiation.

AA amyloidosis treated with tocilizumab: case series and updated literature review.

BACKGROUND: In published case reports, tocilizumab (TCZ) has shown good efficacy for AA amyloidosis in almost all patients. We investigated the efficacy and safety of TCZ in AA amyloidosis in a multicentre study of unselected cases. METHODS: We e-mailed rheumatology and internal medicine departments in France, Switzerland and North Africa by using the Club Rhumatismes Inflammation (CRI) network and the French TCZ registry, Registry RoAcTEmra (REGATE), to gather data on consecutive patients with histologically proven AA amyloidosis who had received at least one TCZ infusion. Efficacy was defined as a sustained decrease in proteinuria level and/or stable or improved glomerular filtration rate (GFR) and by TCZ maintenance. RESULTS: We collected 12 cases of AA amyloidosis treated with TCZ as monotherapy (mean age of patients 63 ± 16.2 years, amyloidosis duration 20.6 ± 31.3 months): eight patients had rheumatoid arthritis (RA), six with previous failure of anti-tumor necrosis factor α (anti-TNF-α) therapy. In total, 11 patients had renal involvement, with two already on hemodialysis (not included in the renal efficacy assessment). For the nine other patients, baseline GFR and proteinuria level were 53.6 ± 32.8 mL/min and 5 ± 3.3 g/24 h, respectively. The mean follow-up was 13.1 ± 11 months. TCZ was effective for six of the eight RA patients (87.5%) according to European League Against Rheumatism response criteria (four good and two moderate responders). As expected, C-reactive protein (CRP) level decreased with treatment for 11 patients. Renal amyloidosis (n = 9) progressed in three patients and was stabilized in three. Overall, three patients showed improvement, with sustained decrease in proteinuria level (42%, 82% and 96%). Baseline CRP level was higher in subsequent responders to TCZ than other patients (p = 0.02). Among the six RA patients with previous anti-TNF-α therapy, amyloidosis was ameliorated in one and stabilized in three. Three serious adverse events occurred (two diverticulitis and one major calciphylaxia due to renal failure). Finally, 7 of 12 (58%) patients continued TCZ. CONCLUSIONS: The efficacy of TCZ for AA amyloidosis varies depending on the inflammatory status at treatment onset. Discrepancies between our study of unselected consecutive patients and reported cases may be due to publication bias. These results support further prospective trials of TCZ for AA amyloidosis.

Treatment response, drug survival and safety of anti-tumour necrosis factor α therapy in 193 patients with psoriatic arthritis: a twelve-year "real life" experience.

OBJECTIVE: To evaluate the performance of anti-TNFα therapy in psoriatic arthritis (PsA) in a routine care setting. METHODS: Inclusion criteria were patients with PsA who initiated anti-TNFα therapy between April 2001 and April 2013 with a follow-up of at least 6 months. For peripheral forms, treatment was considered to be effective for patients with a favourable expert opinion or>30% clinical improvement of swollen and tender joint counts. For axial forms, efficacy criteria were: improvement of BASDAI by at least 2 points on a scale from 0 to 10 or 50% improvement (BASDAI 50) or expert opinion. Drug survival of first anti-TNFα therapy was also investigated. RESULTS: The study included 193 patients (107/86M/F, mean age: 46.8 years, mean disease duration: 6.7 years, 171/22 peripheral/axial forms). Only 48 (25%) patients received concomitant DMARD therapy (65% were treated with methotrexate). The majority of patients started with first-line etanercept (n=102), followed by adalimumab (n=46), infliximab (n=44) and golimumab (n=1). At 3 months, 90% of patients had obtained an adequate response, 7% had discontinued due to lack of efficacy and 3% due to adverse events. Median drug survival was 2 years. One-year and 2-year drug survival rates were 77% and 67%, respectively. Seventy-nine (41%) patients switched to a second anti-TNFα and 29 to a third anti-TNFα; 82% of switchers responded to second-line therapy and 83% responded to third-line therapy. CONCLUSION: High drug survival and high response rates were observed in these patients with PsA receiving their first anti-TNFα therapy in routine clinical practice.

Identification of S100A9 as biomarker of responsiveness to the methotrexate/etanercept combination in rheumatoid arthritis using a proteomic approach.

OBJECTIVES: One way to optimize the drug prescription in rheumatoid arthritis (RA) is to identify predictive biomarkers of drug responsiveness. Here, we investigated the potential "theranostic" value of proteins of the S100 family by monitoring levels of both S100A8 and S100A9 in blood samples from RA patients. DESIGN: For proteomic analysis, peripheral blood mononuclear cells (PBMC) and serum samples were collected in patients prior to initiation of the methotrexate/etanercept (MTX/ETA) combination. Firstly, relative mass spectrometry (MS) quantification focusing on S100A8 and S100A9 proteins was carried out from PBMCs samples to identify potential biomarkers. The same approach was also performed from serum samples from responder (R) and non responder (NR) patients. Finally, to confirm these results, an absolute quantification of S100A8, S100A9 proteins and calprotectin (heterodimer of S100A8/S100A9) was carried out on the serum samples using ELISA. RESULTS: MS analyses revealed that both S100A8 and S100A9 proteins were significantly accumulated in PBMC from responders. In contrast to PBMC, only the S100A9 protein was significantly overexpressed in the serum of R patients. Absolute quantification by ELISA confirmed this result and pointed out a similar expression level of S100A8 protein and calprotectin in sera from both R and NR groups. Thus, the S100A9 protein revealed to be predictive of MTX/ETA responsiveness, contrarily to parameters of inflammation and auto-antibodies which did not allow significant discrimination. CONCLUSION: This is the first report of an overexpression of S100A9 protein in both PBMCs and serum of patients with subsequent response to the MTX/ETA combination. This protein thus represents an interesting biomarker candidate of therapeutic response in RA.

Dosage adjustment of anti-tumor necrosis factor-α inhibitor in ankylosing spondylitis is effective in maintaining remission in clinical practice.

OBJECTIVE: While remission is possible in patients with ankylosing spondylitis (AS), it is often unclear what attitude should be adopted once remission has occurred. We investigated whether dosage adjustment is an effective means of maintaining remission. METHODS: This was a retrospective study drawn from clinical situations. Remission was defined using clinical measures [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≤ 20/100 and no peripheral joint disease] and biological measures [C-reactive protein (CRP) levels ≤ normal value]. The tumor necrosis factor-α (TNF-α) inhibitors used were infliximab, adalimumab, and etanercept. Response predictors of remission were evaluated by logistic regression (age, CRP, HLA-B27 positivity, sex, duration of disease, and anti-TNF-α naivety). CRP and BASDAI were evaluated before and after dosage adjustment at about 6, 12, 24, and 36 months. RESULTS: One hundred eighty-nine patients with AS were included in the study, with a mean followup of 43.5 (± 17.9) months after the introduction of the first anti-TNF-α inhibitor. Mean age was 45.6 (± 12.5) years. Remission had occurred in 65 patients (35%). Significant response predictors of remission were male sex (p = 0.003) and anti-TNF-α naivety (p < 0.001). Dosage adjustment was observed 49 times, and progressively reducing treatment frequency was effective to maintain remission in a large number of patients for 36 months. The cumulative probability of continuing anti-TNF-α after dosage adjustment was 79.0% at 12 months, 70.5% at 24 months, and 58.8% at 36 months. CONCLUSION: Remission had occurred in 35% of the patients with AS under anti-TNF-α inhibitor therapy. Dosage adjustment and progressively reducing treatment frequency was effective in maintaining remission.