False positives in the ultrasound diagnosis of giant cell arteritis: some diseases can also show the halo sign.

OBJECTIVES: To describe the frequency and causes for the presence of a halo sign on the ultrasound of patients without a diagnosis of GCA. METHODS: In total, 305 patients with temporal artery colour Doppler ultrasound showing the presence of halo sign (intima-media thickness ≥0.34 mm for temporal arteries [TAs] and ≥1 mm for axillary arteries) were included, and their medical records were reviewed. The clinical diagnosis based on the evolution of the patient over at least one year was established as the definitive diagnosis. RESULTS: Fourteen of the 305 (4.6%) patients included showed presence of the halo sign without final diagnosis of GCA: 12 patients in the TAs (86%), and two patients with isolated AAs involvement (14%). Their diagnoses were PMR (n = 4, 29%); atherosclerosis (n = 3, 21%); and non-Hodgkin lymphoma type T, osteomyelitis of the skull base, primary amyloidosis associated with multiple myeloma, granulomatosis with polyangiitis, neurosyphilis, urinary sepsis and narrow-angle glaucoma (n = 1 each, 7%). CONCLUSION: The percentage of halo signs on the ultrasound of patients without GCA is low, but it does exist. There are conditions that may also show the halo sign (true positive halo sign), and we must know these and always correlate the ultrasound findings with the patient's clinic records.

Infusion reactions during infliximab treatment are not associated with IgE anti-infliximab antibodies.

OBJECTIVES: Controversy exists on the role of IgE antidrug antibodies (IgE-ADA) in infusion reactions (IR) on infliximab treatment, partly due to the lack of a positive control used for assay validation. We sought to (1) develop a robust assay to measure IgE-ADA, including a positive control, (2) determine the association between IgE-ADA and IR and (3) determine the incidence of IgE-ADA in infliximab treated patients. METHODS: A recombinant human IgE anti-infliximab monoclonal antibody was developed as standard and positive control. With this antibody, we set up a novel robust assay to measure IgE-ADA. IgE-ADA was determined in three retrospective cohorts (n=159) containing IR+ (n=37) and IR- (n=39), and longitudinal sera of 83 spondyloarthritis. RESULTS: IgE-ADA was found in 0/39 IR-, whereas 4/37 (11%) IR+ showed low levels (0.1-0.3 IU/mL, below the 0.35 IU/mL threshold associated with elevated risk of allergic symptoms). All patients who were IgE-ADA positive also had (very) high IgG-ADA levels. The incidence of IgE-ADA in patients with infliximab-treated spondyloarthritis was estimated at less than approximately 1%. CONCLUSIONS: IgE-ADA is rarely detected in infliximab-treated patients. Moreover, the absence of IgE-ADA in the majority of IR+ patients suggests that IgE-ADA is not associated with infusion reactions.

Current Practice for Therapeutic Drug Monitoring of Biopharmaceuticals in Rheumatoid Arthritis.

The treatment of rheumatoid arthritis (RA) has largely improved in the biopharmaceutical era. These compounds, primarily tumor necrosis factor (TNF) inhibitors, are effective, but some patients may show poor response, sometimes because of the presence of antidrug antibodies (ADAs). In some instances, clinicians may increase or taper the dose depending on the clinical response. Besides the current clinical-based practice, a tailored strategy based on drug monitoring has emerged as a way to improve the use of these drugs. However, the relevance of this therapeutic drug monitoring (TDM) of biopharmaceuticals in RA is still unknown. In this literature review, we examine the most relevant articles dealing with the concentration-response relationship, ADA detection and pharmacokinetics in RA patients receiving biopharmaceuticals. A concentration-response relationship was clearly established for TNF inhibitors. Moreover, ADA positivity was associated with low drug concentrations, poor clinical outcome, and reduced drug survival for TNF-inhibitor monoclonal antibodies. Concomitant use of disease-modifying antirheumatic drugs, especially methotrexate, is associated with good clinical outcome, increased drug concentrations, and reduced immunogenicity. Strategies based on TDM of TNF inhibitors seem promising for RA, but randomized controlled trials are required to support this. A concentration-response relationship may exist with tocilizumab, and immunogenicity seems rare. Finally, the relevance of TDM for RA patients receiving rituximab and abatacept remains unclear.

Current Practice for Therapeutic Drug Monitoring of Biopharmaceuticals in Spondyloarthritis.

Treatment of spondyloarthritis (SpA) has greatly improved in the biopharmaceutical era. These compounds, primarily tumor necrosis factor inhibitors, are effective, but some patients may show poor response, sometimes due to the presence of antidrug antibodies (ADAs). In some instances, clinicians may increase or taper the dose, depending on the clinical response. Besides the current clinical practice, a tailored strategy based on drug monitoring is emerging as a way to improve the use of these drugs. However, the relevance of this therapeutic drug monitoring of biopharmaceuticals for SpA is still unknown. In this literature review, we examined the most relevant articles dealing with the concentration-response relation, ADA detection, and pharmacokinetics in SpA treated with biopharmaceuticals. ADAs were associated with low or undetectable concentration of monoclonal antibodies. The relation between drug concentration and clinical response in SpA is debated, some studies showing an association and others not. Therefore, therapeutic drug monitoring of biopharmaceuticals for SpA requires a better understanding of the association among the pharmacokinetics, pharmacodynamics, and immunogenicity of these drugs.

Color Doppler and spectral Doppler ultrasound detection of active sacroiliitis in spondyloarthritis compared to physical examination as gold standard.

Sacroiliac joint (SIJ) involvement is a distinctive feature of spondyloarthritis (SpA). The main objective of this study was to assess the validity of color Doppler ultrasound (CDUS) in SIJ. This was a cross-sectional, blinded, case-control study of 108 cases divided into three groups: (a) 53 SpA patients with inflammatory back pain (IBP); (b) 28 SpA patients with no IBP; and (c) 27 healthy mechanical lumbar pain subjects. Physical examinations of the SIJs were assessed as positive or negative in each SIJ and were used as the gold standard. SIJs were examined with CDUS and spectral Doppler, and the SIJs were assessed as positive when both color Doppler and the resistance index (RI) were less than the cut-off point within the SIJs area. A total of 108 cases (53 female; mean age 36 ± 10 years old) were studied. The physical examination of the SIJs was positive in 38 patients (59 SIJs). Ultrasound detected Doppler signal within the SIJs in 37 cases (58 SIJs): 33 of them had symptomatic SpA (52 SIJs), 3 of them had asymptomatic SpA (5 SIJs), and 1 was a healthy control (1 SIJ). The accuracy of CDUS, when compared to physical SIJ examination, at the patient level in the overall group had a sensitivity of 70.3%, a specificity of 85.7%, a positive likelihood ratio of 4.9, and a negative likelihood ratio of 0.36. For the spectral Doppler RI, with an optimal cut-off point ≤0.75, the sensitivity was 76.2%, and the specificity was 77.8%. CDUS of SIJs seems to be a feasible and valid method for detecting active inflammation in patients with SpA.

Antibodies to infliximab in Remicade-treated rheumatic patients show identical reactivity towards biosimilars.

OBJECTIVES: The aim of this study was to determine whether antibodies to infliximab (IFX) in Remicade-treated patients cross-react with the biosimilar CT-P13. METHODS: 250 consecutive patients with rheumatic diseases under Remicade and 77 controls were retrospectively selected for the study. Anti-IFX antibodies at drug through levels were measured in parallel with three different bridging ELISA assays: Promonitor-ANTI-IFX kit, which uses Remicade to detect antibodies, and two more assays that use either Inflectra or Remsima with the same format. Correlation and association between each assay was studied. RESULTS: 50.4% of patients were tested positive with Promonitor-ANTI-IFX. All were antibodies to IFX (ATI)-positive when either Inflectra or Remsima assays were used. In all comparisons positive and negative percentage agreements were 100%, and correlation coefficients were ≥0.995. No differences between rheumatoid arthritis and spondyloarthritis, or between concomitant immunosuppressives, were observed. CONCLUSIONS: Anti-IFX antibodies of Remicade-treated patients cross-react with either Inflectra or Remsima. Although additional epitopes may be present in the biosimilar, results suggest that epitopes influencing the immune response to IFX are also present in the biosimilar. Antibody-positive patients treated with Remicade should not be switched to the biosimilar, since antibodies will interact with the new drug and potentially lead to loss of response. This finding supports the utility for therapeutic drug monitoring before a switching strategy is considered.

Comparing a tapering strategy to the standard dosing regimen of TNF inhibitors in rheumatoid arthritis patients with low disease activity.

OBJECTIVES: The aim of this study is to compare clinical outcomes, incidence of flares and administered drug reduction between rheumatoid arthritis (RA) patients under TNF inhibitors (TNFi) tapering strategy and RA patients on standard regimen. METHODS: Two groups of RA patients on TNFi with DAS28<3.2 were compared: the tapering group (TG: 67 pts from Spain) and the control group with standard therapy regimen (CG: 77 pts from the Netherlands). DAS28 was measured at different time points: visit 0 (prior starting TNFi), visit 1 (prior to start tapering in TG and with DAS28<3.2 in TG and CG), visit 2 (6 months after visit 1), visit 3 (1 year after visit 1), visit 4 (the last visit available after visit 1) and visit-flare (visit with the worst flare between visit 1 and visit 4). RESULTS: Despite the reduction of administered drug at visit 4 in the TG (interval elongation of 32.8% in infliximab, 52.9% in adalimumab and 52.6% in etanercept), the DAS28 remained similar between groups at the end of the study (DAS28: 2.7±0.9 in TG vs. 2.5±1 in CG, p=0.1). No differences were seen in the number of patients with flares [26/67 (38.9%) in the TG vs. 30/77 (39%) in the CG, p=0.324] and only nineteen out of 136 patients (14%) had anti-drug antibodies at the end of the study. CONCLUSIONS: The tapering strategy of TNFi in RA patients result in a reduction of the drug administered, while the disease control is not worse than patients on the standard regimen.

Influence of immunogenicity on the efficacy of longterm treatment of spondyloarthritis with infliximab.

BACKGROUND: Infliximab (IFX) is a monoclonal antibody against tumour necrosis factor α that is effective for treating spondyloarthritis (SpA). However, after initial success of the drug some patients lose responsiveness or develop infusion reactions, which may be related to the development of antibodies against the drug. OBJECTIVE: To investigate the clinical relevance of antibodies to infliximab (ATI) formation in patients with SpA undergoing IFX treatment over a prolonged period. METHODS: 94 patients with SpA treated with IFX from 1999 to 2010 were studied. Their clinical characteristics, serum trough IFX levels and ATI status were evaluated for a mean of 6.99 (95% CI:6.28 to 7.7) years. Clinical activity and improvement were measured using the Ankylosing Spondylitis Disease Activity Score (ASDAS): inactive <1.3, moderate ≥1.3 and <2.1, high ≥2.1-≤3.5, and very high >3.5 at three time points (6 months, 12 months and >4 years). RESULTS: ATI were detected in 24 (25.5%) patients. The patients with ATI had higher ASDAS scores than those without ATI (2.55±0.89 vs 1.79±1.04, p=0.038 at 6 months; 1.95±0.67 vs 1.67±0.71, p=0.042 at 1 year; 2.52±0.99 vs 1.53±0.81, p=0.024 at >4 years). Eleven patients (12%) developed infusion-related reactions, and of these, ATI were present in eight patients (73%). The patients with infusion-related reactions had higher ATI titres (median 12 931 AU/ml, IQR 853-82 437) vs median 2454 AU/ml, IQR 449-7718, p=0.028) and shorter survival (4.25 years vs 8.19 years, p<0.001). ATI development occurred more frequently in the patients not receiving methotrexate (20/58 (34.5%) vs 4/36 (11.1%), p=0.011). CONCLUSION: In patients with SpA treated with IFX, ATI formation is associated with a poor clinical response, the appearance of infusion reactions and the discontinuation of treatment.

Pathogenic mechanisms involving the interplay between adipose tissue and auto-antibodies in rheumatoid arthritis.

We aimed to evaluate the association between adipose tissue (AT) dysfunction, autoimmunity, and disease activity in rheumatoid arthritis (RA). A cross-sectional study including 150 RA patients and 50 healthy donors and longitudinal study with 122 RA patients treated with anti-tumor necrosis factor (TNF)-α, anti-interleukin 6 receptor (IL6R) or anti-CD20 therapies for 6 months were carried out. In vitro experiments with human AT and adipocyte and macrophage cell lines were performed. A collagen-induced arthritis mouse model was developed. The insulin resistance and the altered adipocytokine profile were associated with disease activity, the presence of anti-citrullinated proteins anti-bodies (ACPAs), and worse response to therapy in RA. AT in the context of arthritis is characterized by an inflammatory state alongside the infiltration of macrophages and B/plasmatic cells, where ACPAs can have a direct impact, inducing inflammation and insulin resistance in macrophages and promoting a defective adipocyte differentiation, partially restored by biologicals.

Enthesis erosion in spondyloarthritis is not a persistent structural lesion.

OBJECTIVE: To evaluate the ability of ultrasound (US) to detect the presence and change of Achilles erosions in spondyloarthritis (SpA). METHODS: A blind prospective two-dimensional (2D) and three-dimensional (3D) US study of Achilles enthesis erosions in early SpA was undertaken. US examinations were performed at baseline and at 6 and 12 months of follow-up. Clinical outcomes measures were collected. RESULTS: Bilateral Achilles entheses of 68 patients (35 women) were investigated. The mean Bath Ankylosing Spondylitis Disease Activity Index and C reactive protein (CRP) levels were 4.58 ± 2.05 and 5.97 ± 9.91 mg/l, respectively. The κ values for intrareader agreement for 2D and 3D images were 0.84 and 0.85 for two readers. 2D US visualised 10 erosions (7.4%) and 3D US visualised 13 erosions (9.6%) in 10 patients (14.7%). At 6 and 12 months of follow-up, 25% and 50% of basal erosions had disappeared, respectively and, of the new erosions that appeared at 6 months, 40% had disappeared 6 months later. A statistically significant association between erosion and CRP levels, entheseal Doppler signals and the number of tender and swollen joints was found. CONCLUSIONS: US examination of Achilles erosions is reliable and sensitive to change. An association was found between Achilles erosions and objective activity-based measurements of SpA outcomes.

Influence of immunogenicity on the efficacy of long-term treatment with infliximab in rheumatoid arthritis.

OBJECTIVE: To analyse the clinical relevance of the production of anti-infliximab antibodies (anti-infliximab Abs) in patients with RA undergoing infliximab treatment over a prolonged period of time. METHODS: Clinical characteristics, serum trough infliximab and antibody levels were evaluated in 85 RA patients treated with infliximab for a median of 4.42 (interval 0.4-10.2) years. DAS in 28 joints (DAS-28), EULAR response criteria and survival of treatment were assessed at 3 time points (6 months, 12 months and >4 years). RESULTS: Antibodies against infliximab were detected in 28 (32.9%) patients and were present in all EULAR non-responder patients. Antibody levels were higher in EULAR non-responders throughout the study period (P = 0.05 at 6 months, P = 0.02 at 1 year, P = 0.003 at >4 years) compared with EULAR (good and moderate) responders. Nine (10.5%) patients, all of them with high-serum anti-infliximab Ab levels, developed infusion-related reactions. Patients with anti-infliximab Abs more often required increased infliximab doses (51.7%) (P = 0.032) and median survival time on treatment was shorter (4.15 vs 8.89 years) (P = 0.0006). MTX co-therapy was not associated with lower proportion of anti-infliximab Ab-positive patients, but those receiving both infliximab and MTX had lower levels of anti-infliximab Abs (P = 0.073) and longer survival (P = 0.015) on treatment. CONCLUSION: The formation of anti-infliximab Abs during treatment with infliximab is associated with a loss of clinical response, the appearance of infusion reactions and discontinuation of treatment.

Doppler enthesitis: a potential useful outcome in the assessment of axial spondyloarthritis and psoriatic arthritis.

OBJECTIVE: To analyse the frequency of power Doppler (PD) enthesitis in active axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) patients and its potential usefulness in clinical practice. METHODS: A prospective multicentre cross-sectional study in patients with axSpA and PsA with active disease was undertaken. Patients underwent bilateral ultrasound (US) examination of the peripheral entheses according to the Madrid Sonographic Enthesis Index (MASEI). The MASEI and Outcome Measures in Rheumatology (OMERACT) PD enthesitis definitions were checked. An inter-reader analysis of recorded videos was performed to determine reliability. RESULTS: Sixty-four consecutive patients were included. The mean DAS28 (3.9 ± 1.3) for peripheral involvement, mean BASDAI (5.6 ± 2.2) for axial involvement, and CRP values (10 ± 10.9) reflected moderate-high disease activity at baseline. The mean global MASEI score was 29.4 (± 11.4), and 55 patients (86%) scored ≥ 18 (proposed cut-off point to diagnose SpA). At the patient level, abnormal US findings consistent with at least one enthesis showing a PD signal were observed in 52 (81.3%) patients using the MASEI PD definition and 48 (75%) using the OMERACT PD definition, without significant variation between axSpA and PsA. The inter-reader reliability was excellent (kappa = 0.92 for MASEI PD and 0.86 for OMERACT PD). CONCLUSIONS: PD enthesitis was found in the majority of patients with active axSpA and PsA, independent of axial or peripheral affectation. Both MASEI and OMERACT PD definitions were useful in detecting active enthesitis. These findings support the usefulness of a PD US evaluation of entheses in the assessment of axSpA and PsA. Key Points • PD enthesitis is a very common finding in patients with active axSpA and PsA • Both MASEI and OMERACT PD definitions are useful to detect active enthesitis • US enthesitis may reveal information in axSpA and PsA.

Cost evolution of biological drugs in rheumatoid arthritis patients in a tertiary hospital: Influential factors on price.

OBJECTIVE: To assess the evolution of cost per patient/year and the cost per patient/year/drug in patients with rheumatoid arthritis (RA) receiving biological treatments. To analyze and quantify the factors influencing this evolution, such as the optimization of the biological drugs, the use of biosimilars, and official discounts and discounts obtained after negotiated procedures. In addition, to assess specific clinical parameters of disease activity in these patients. METHODS: Retrospective, observational study conducted in a Spanish tertiary hospital. Adult patients diagnosed with RA under treatment from 2009 to 2017 were included. RESULTS: 320, 270 and 389 patients were included in 2009, 2013 and 2017, respectively. The patient/year cost decreased from 10,789€ in 2009, 7491€ in 2013 to 7116€ in 2017. In 2017, due to the established competition, discounts of 14% and 29.5% were achieved on etanercept and its biosimilar; 11.5%, 17.8%, 17.9%, 17.3% on adalimumab, certolizumab, golimumab and tocilizumab IV respectively, and 24.6% and 43.1% on infliximab and its biosimilar. The percentage of patients optimized in 2017 was 35.2%. The annual saving in 2017 was 1,288,535€ (830,000€ due to dose optimization and/or administration regimens, 249,666€ corresponding to 7.5% of the official discount and 208,868€ after negotiated procedures). CONCLUSION: The annual cost per patient in RA decreased considerably due to different factors, such as discounts on the purchase of drugs due to official discounts and negotiated procedures, together with the optimization of therapies, the latter being the factor that contributed most to this decrease.

Clinical predictors of multiple failure to biological therapy in patients with rheumatoid arthritis.

BACKGROUND: Biological therapies have improved the clinical course and quality of life of rheumatoid arthritis (RA) patients. Despite the availability and effectiveness of these treatments, some patients experience multiple failures to biologic disease-modifying antirheumatic drugs (bDMARDs), constituting a particular challenge to clinicians. OBJECTIVES: This study aims to determine the percentage of rheumatoid arthritis (RA) patients who fail to respond to subsequent bDMARDs, describe their characteristics, and identify specific baseline and early features during the first bDMARD as possible predictors of consecutive multiple bDMARD failure. METHODS: This is a longitudinal study involving RA patients from the prospective biological cohort drawn from the La Paz University Hospital RA Registry (RA-Paz), starting a bDMARD during the years 2000 to 2019. Patients who presented insufficient response (due to primary or secondary inefficacy) to at least three bDMARDs or two bDMARDs with different mechanism of action were considered multi-refractory (MR-patients). Patients who achieved low disease activity or remission (by DAS-28) with the first bDMARD and maintained this over a follow-up period of at least 5 years were considered non-refractory (NR-patients). RESULTS: A total of 41 out of 402 (10%) patients were MR-patients and 71 (18%) NR-patients. In the multivariate analysis, the presence of erosions, younger age, higher baseline DAS-28 and mostly achieving delta-DAS < 1.2 after 6 months of the first bDMARD (OR 11.12; 95% CI 3.34-26.82) were independently associated with being MR-patients to bDMARDs. CONCLUSIONS: In our cohort, 10% of patients with RA were observed to have multi-refractoriness to bDMARDs. This study supports the contention that younger patients with erosive disease and especially the early absence of clinical response to the first bDMARDs are predictors of multi-refractoriness to consecutive biologics. Hence, patients with these characteristics should be monitored more closely and may benefit from personalized treatments.

Cost evolution of biological agents for the treatment of spondyloarthritis in a tertiary hospital: influential factors in price.

Background Spending on biological agents has risen dramatically due to the high cost of the drugs and the increased prevalence of spondyloarthritis. Objective To evaluate the annual cost per patient and cost for each biological drug for treating patients with spondyloarthritis from 2009 to 2016, and to calculate factors that affect treatment cost, such as optimizing therapies by monitoring drug serum levels, the use of biosimilar-TNF inhibitors, and official discounts or negotiated rebates in biologicals acquired by the pharmacy department. Method Retrospective, observational study in a Spanish tertiary hospital. Main outcome Annual cost per patient and per drug. Factors that influenced the costs and socio-demographic parameters and disease activity. Results A total of 129, 215, and 224 patients were treated in 2009, 2013, and 2016, respectively. The annual cost per patient decreased: EUR11,604 in 2009, EUR8513 in 2013, and EUR7464 in 2016. The introduction of new drugs drives economic competition, leading to total savings per drug, with discounts reaching 5.8, 12.4, 16.7, 17.7, 13.7, and 24.8% for original infliximab, etanercept, adalimumab, ertolizumab, golimumab, and secukinumab, respectively, while rebates for biosimilar infliximab reached 31.90% in 2016. The number of patients with optimized therapies reached 47.5% in 2016, which led to cost savings of EUR798,614, in addition to savings from official discounts and rebates of EUR252,706 and savings from optimized therapies of EUR545,908 in 2016. Conclusion The cost of biological treatments declined after official discounts, negotiated rebates, and optimized therapies, leading to a significant decrease in the annual cost per patient. The greatest contribution to economic savings in biological therapy according to our study was biological therapy optimization.

Cost evolution of biological drugs in rheumatoid arthritis patients in a tertiary hospital: Influential factors on price / Evolución del coste de medicamentos biológicos en pacientes con artritis reumatoide en un hospital terciario. Factores influyentes en dicha evolución

Objective: To assess the evolution of cost per patient/year and the cost per patient/year/drug in patients with rheumatoid arthritis (RA) receiving biological treatments. To analyze and quantify the factors influencing this evolution, such as the optimization of the biological drugs, the use of biosimilars, and official discounts and discounts obtained after negotiated procedures. In addition, to assess specific clinical parameters of disease activity in these patients. Methods: Retrospective, observational study conducted in a Spanish tertiary hospital. Adult patients diagnosed with RA under treatment from 2009 to 2017 were included. Results: 320, 270 and 389 patients were included in 2009, 2013 and 2017, respectively. The patient/year cost decreased from 10,789€ in 2009, 7491€ in 2013 to 7116€ in 2017. In 2017, due to the established competition, discounts of 14% and 29.5% were achieved on etanercept and its biosimilar; 11.5%, 17.8%, 17.9%, 17.3% on adalimumab, certolizumab, golimumab and tocilizumab IV respectively, and 24.6% and 43.1% on infliximab and its biosimilar. The percentage of patients optimized in 2017 was 35.2%. The annual saving in 2017 was 1,288,535€ (830,000€ due to dose optimization and/or administration regimens, 249,666€ corresponding to 7.5% of the official discount and 208,868€ after negotiated procedures). Conclusion: The annual cost per patient in RA decreased considerably due to different factors, such as discounts on the purchase of drugs due to official discounts and negotiated procedures, together with the optimization of therapies, the latter being the factor that contributed most to this decrease.(AU)

Objetivo: Evaluar la evolución del coste por paciente/año y del coste por paciente/año/medicamento en pacientes en tratamientos con biológicos con artritis reumatoide (AR). Analizar y cuantificar los factores influyentes en dicha evolución tales como la optimización de medicamentos biológicos, el uso de biosimilares y los descuentos oficiales y los obtenidos tras procedimientos negociados. Además, evaluar parámetros clínicos de la actividad propios de la enfermedad en dichos pacientes. Métodos: Estudio retrospectivo, observacional, realizado en un hospital terciario español. Se incluyeron pacientes adultos diagnosticados de AR en tratamiento con biológicos desde 2009 a 2017. Resultados: Se incluyeron 320, 270 y 389 pacientes en 2009, 2013 y 2017, respectivamente. El coste paciente/año disminuyó de 10.798€ en 2009, 7.491€ en 2013 a 7.116€ en 2017. En 2017, debido a la competencia establecida, se alcanzaron descuentos del 14 y del 29,5% en etanercept y su biosimilar; 11,5, 17,8, 17,9 y 17,3% en adalimumab, certolizumab, golimumab y tocilizumab IV, respectivamente, así como un 24,6% y 43,1% en infliximab y su biosimilar. El porcentaje de pacientes optimizados en 2017 alcanzó el 35.2%. El ahorro anual en 2017 fue de 1.288.535€ (830.000€ debido a la optimización de dosis y/o pautas de administración, 249.666€ correspondiente al 7,5% del descuento oficial y 208.868€ tras procedimientos negociados). Conclusión: El coste anual por paciente en AR disminuyó considerablemente debido a diferentes factores, tales como, descuentos en la adquisición de medicamentos debido a descuentos oficiales y procedimientos negociados, junto a la optimización de terapias, siendo este último el factor que más contribuyó en dicho descenso.(AU)

Effect of Infliximab Dose Increase in Rheumatoid Arthritis at Different Trough Concentrations: A Cohort Study in Clinical Practice Conditions.

BACKGROUND: Evidence supporting treatment intensification in rheumatoid arthritis (RA) is limited and controversial. We explored outcomes of infliximab dose increases and accounted for pre-existing trough levels in patients with active RA. METHODS: This study was a retrospective study of 42 RA patients who received increased infliximab following an insufficient response (DAS28 >3.2). Serum concentrations of infliximab and antibodies to infliximab (ATI) and DAS28 and EULAR clinical response parameters were recorded for 1 year. Analyses were performed in three patient groups that were defined by infliximab serum concentration prior to treatment enhancement: no detectable, low (<1.1 µg/mL) or high (≥1.1 µg/mL) drug levels. RESULTS: No circulating infliximab was detected in 20 patients (47.6%), but 13 (31%) and 9 (21.4%) patients exhibited low and high levels, respectively. ATI was only detected in patients with no detectable drug levels because the drug interferes with ELISA. DAS28 disease activity globally showed a modest improvement after dose escalation, but this improvement did not persist after 6 and 12 months. Infliximab serum levels increased significantly in the high group (p = 0.016), but no increase was achieved in the low and no detectable groups. The three study groups exhibited similar disease activity over time, and no improvement was observed in the non-responder EULAR rates. CONCLUSION: These results suggest that the efficacy of an infliximab dose increase is limited, and the response is independent of the infliximab trough serum concentration that is achieved prior to escalation.