Real-world apremilast use in biologic-naïve psoriatic arthritis patients. Data from Spanish clinical practice.

INTRODUCTION: Apremilast is approved for treatment of psoriasis and psoriatic arthritis (PsA). Real-world evidence on apremilast effectiveness in clinical practice is limited. METHODS: Observational study enrolling adult patients, across 21 Spanish centres, who had initiated apremilast in the prior 6 (±1) months and were biologic naive. Data were collected at routine follow-up visits 6 and 12 months after apremilast initiation. Primary outcome was 6 and 12-month persistence to apremilast. Secondary outcomes included Disease Activity for PsA (DAPSA), joint erosions, enthesitis, dactylitis, and patient-reported quality of life (QoL, measured using the PsA impact of disease [PsAID] questionnaire). RESULTS: We included 59 patients. Most had oligoarticular PsA, moderate disease activity, and high comorbidity burden. Three-quarters were continuing apremilast at 6 months and two-thirds at 12 months; mean (SD) apremilast treatment duration was 9.43 (1.75) months. DAPSA scores showed improved disease activity: one-third of patients in remission or low activity at apremilast initiation versus 62% and 78% at 6 and 12 months, respectively. Eleven of 46 patients with radiographic assessments had joint erosions at apremilast initiation and none at month 12. Median (Q1, Q3) number of swollen joints was 4.0 (2.0, 6.0) at apremilast initiation versus 0.0 (0.0, 2.0) at 12 months. Incidence of dactylitis and enthesitis decreased between apremilast initiation (35.6% and 28.8%, respectively) and month 12 (11.6% and 2.4%, respectively). Over two-thirds of patients had a PSAID-9 score <4 (cut-off for patient-acceptable symptom state) at month 12. CONCLUSIONS: In Spanish clinical practice, two-thirds of PsA patients continued apremilast at 12 months, with clinical benefits at the joint level, no radiographic progression of erosions, and a positive impact on patient-reported QoL. Trial registration number Clinicaltrials.gov: NCT03828045.

Efficacy of Tofacitinib in the Treatment of Psoriatic Arthritis: A Systematic Review.

INTRODUCTION: Therapeutic approaches for psoriatic arthritis (PsA) include non-pharmacologic therapies, symptomatic treatments, tumor necrosis factor inhibitors, interleukin inhibitors, cytotoxic T lymphocyte antigen 4 immunoglobulin, and Janus kinase inhibitors. This systematic review aimed to provide complete and up-to-date information on efficacy of tofacitinib in the treatment of PsA, giving special attention to non-skin manifestations (peripheral arthritis, axial disease, enthesitis, and dactylitis). METHODS: A search of studies published between January 2016 and June 2020 was carried out on PubMed and Google Scholar. RESULTS: The number of studies with tofacitinib in PsA is limited and most of them are post hoc analyses from OPAL Broaden and OPAL Beyond. Tofacitinib has been demonstrated to be efficacious for the treatment of all disease manifestations in PsA. Superior effectivity to placebo is achieved at the earliest time point evaluated, and maintained over time. Patients who switch from placebo to tofacitinib show the same improvements; however, the time to initial response is faster in patients who firstly receive tofacitinib, compared with those switching subsequently. Additional data suggest that tofacitinib may be also effective for the treatment of the axial domain. CONCLUSIONS: Tofacitinib has been demonstrated to be efficacious for the treatment of peripheral and axial involvement, enthesitis, and dactylitis manifestation in PsA. Further prospective and long-term studies are required to corroborate and complete the present results. Similarly, real-world evidence is also necessary to complement the information obtained in clinical trials, and thereby to have a better overview of real efficacy and safety of the drug.

Atlas of axial spondyloarthritis in Spain 2017: Study design and population.

OBJECTIVE: Atlas of Axial Spondyloarthritis in Spain 2017 aims to better understand the reality of the patients suffering from this disease from an integrated approach. METHODS: The Atlas 2017 based its results on an extensive cross-sectional patient survey conducted in Spain (2016), validated by a multidisciplinary group of experts on spondyloarthritis. RESULTS: Data from 680 patients with axSpA were obtained, most of them suffered from AS, were HLA-B27 positive, older than 45 years, and live as part of a couple. A large percentage had university studies, were disabled and members of a patient association. Patients reported a diagnostic delay of 8.5 years, high disease activity (BASDAI 5.5±2.2), moderate-important stiffness (61.0%), medium-high functional limitation (74.9%), and psychological distress (GHQ 5.7±4.5). A total of 54.7% reported taking NSAIDs, 28.4% DMARDs, 36.3% biological therapy and 32.2% were not receiving pharmacological treatment. CONCLUSIONS: The Atlas survey data reveals still a long diagnostic delay, high disease activity, psychological distress, while an important proportion could be undertreated.

Influence of HLA-B27 on the Ankylosing Spondylitis phenotype: results from the REGISPONSER database.

OBJECTIVE: To assess HLA-B27 influence on the clinical phenotype of Ankylosing Spondylitis (AS) patients. METHOD: An observational, cross-sectional and descriptive study of AS patients from the Spanish REGISPONSER database was performed. Demographic, clinical, disease activity (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP)), and radiographic data (Bath Ankylosing Spondylitis Radiology Index (BASRI) score) were compared regarding HLA-B27 status. A univariate and multivariate analysis was performed to identify variables independently related to the presence of HLA-B27. RESULTS: Data from 1235 patients (74.8% male) were analyzed; 1029 were HLA-B27 positive (83%). HLA-B27-positive patients showed higher family aggregation and an earlier onset of disease compared with those who were HLA-B27 negative. HLA-B27-negative patients presented statistically higher BASDAI and BASFI scores and higher prevalence of arthritis, dactylitis, and extra-articular manifestations (psoriasis and inflammatory bowel disease (IBD)) but not anytime uveitis compared with those who were HLA-B27 positive. In the multivariate analysis, family history (odds ratio (OR) 2.10, 95% confidence interval (CI) 1.27-3.49), younger age at diagnosis (OR 0.97, 95% CI 0.96-0.98), presence of peripheral arthritis (OR 0.53, 95% CI 0.32-0.89), dactylitis (OR 0.16, 95% CI 0.05-0.56), psoriasis (OR 0.45, 95% CI 0.26-0.78), and IBD (OR 0.22, 95% CI 0.12-0.40) were the main variables independently related to the presence or not of HLA-B27. CONCLUSION: In Caucasian AS patients, the presence of HLA-B27 is related to an earlier disease onset and higher family aggregation. Absence of HLA-B27 is related to a higher frequency of peripheral arthritis, dactylitis, and extra-articular manifestations. Being HLAB27 positive is not related to a higher burden of disease or anytime uveitis.

Points to Consider in the Foundation of Multidisciplinary Units for Psoriatic Arthritis: A Delphi Study and a Systematic Review of the Literature.

INTRODUCTION: In numerous clinical practice guidelines, emphasis is placed on the need for coordinated care of psoriatic arthritis (PsA) between rheumatologists and the objective was to develop experience-based points to consider facilitating the implementation of multidisciplinary units (Dermatology/Rheumatology) for the management of patients with PsA. METHODS: A scientific committee of rheumatology and dermatology experts in the management of PsA, and with experience in joint care, discussed the critical aspects of multidisciplinary PsA Units. The discussion became the basis for a Delphi survey in two rounds submitted to a panel of 24 specialists in rheumatology and dermatology not involved in PsA units. The statements and practices that reached a consensus were summarized and further elaborated. RESULTS: After two Delphi rounds, agreement was reached for 49 of the 50 proposed statements. These included a justification of the units, objectives, and utilities, as well as operational aspects of the units, such as the minimal and ideal premises, referral criteria, and necessary resources. The statements were compiled in 11 points to consider. CONCLUSIONS: This consensus offers some points to consider, including premises and recommendations, for the development of specialized Units in the management of PsA based on expert opinion. We trust these guidelines may facilitate their implementation in the future. FUNDING: Pfizer.

Reccomendations for the detection, study and referral of inflammatory low-back pain in primary care.

OBJECTIVE: To design a strategy for the early detection and referral of patients with possible spondyloarthritis based on recommendations developed, agreed upon, and directed to primary care physicians. METHODS: We used a modified RAND/UCLA methodology plus a systematic literature review. The information was presented to a discussion group formed by rheumatologists and primary care physicians. The group studied the process map and proposed recommendations and algorithms that were subsequently submitted in two Delphi rounds to a larger group of rheumatologists and primary care physicians. The final set of recommendations was derived from the analysis of the second Delphi round. RESULTS: We present the recommendations, along with their mean level of agreement, on the early referral of patients with possible spondyloarthritis. The panel recommends that the study of chronic low back pain in patients under 45 years be performed in four phases 1) clinical: key questions, 2) clinical: extra questions, 3) physical examination, and 4) additional tests. CONCLUSIONS: The level of agreement with these simple recommendations is high. It is necessary to design strategies for the education and sensitization from rheumatology services to maintain an optimal collaboration with primary care and to facilitate referral to rheumatology departments.

ASDAS high disease activity versus BASDAI elevation in patients with ankylosing spondylitis as selection criterion for anti-TNF therapy.

OBJECTIVE: To investigate which of the 2 ankylosing spondylitis (AS) disease activity instruments identifies better those patients with characteristics that have been associated with positive response to anti-TNF therapy. METHODS: Data from patients with AS in the REGISPONSER registry were analyzed. Patients were categorized by disease activity using 3 different selection criteria: elevated Bath Ankylosing Spondylitis Disease Activity Index criteria (BASDAI≥4), high Ankylosing Spondylitis Disease Activity Score (ASDAS≥2.1), or very high ASDAS (ASDAS≥3.5). To determine which criterion selects for patients most likely to respond to anti-TNF therapy, the groups of patients selected with each criterion were compared on five disease characteristics that are associated with good response to anti-TNF therapy: lower age, lower function score, less enthesitis, higher C-reactive protein (CRP), and HLA-B27-positive status. RESULTS: 50.9%, 66.3%, and 24.9% of 1156 patients had elevated BASDAI, high ASDAS, or very high ASDAS, respectively. Compared to patients selected with elevated BASDAI, more patients selected with high ASDAS had characteristics associated with good response to anti-TNF therapy. Patients with very high ASDAS had higher CRP and were younger, but more frequently had enthesitis and had higher function scores when compared to those with elevated BASDAI. CONCLUSIONS: Selection of AS patients with the ASDAS instrument results in patient sub-populations with different characteristics than those selected with the BASDAI instrument. Since some of these characteristics have been associated with response to anti-TNF therapy, further study should establish if the choice of selection instrument improves the outcome of therapy in the selected populations.

Different clinical expression of patients with ankylosing spondylitis according to gender in relation to time since onset of disease. Data from REGISPONSER.

OBJECTIVE: To describe the differential characteristics by gender and time since disease onset in patients diagnosed with ankylosing spondylitis (AS) attending the Spanish rheumatology clinics, including those on the "Spanish Registry of spondyloarthritis" (REGISPONSER), as well as the diagnostic and therapeutic implications that this entails. PATIENTS AND METHODS: This is a transversal and observational study of 1514 patients with AS selected from 2367 spondyloarthritis cases included in REGISPONSER. For each patient, the demographics, epidemiology, geriatric, clinical, laboratory, radiological, and therapeutic aspects were were evaluated and comprehensively recorded under the aegis of REGISPONSER, constituting the Minimum Basic identifying data for the disease. Physical function was assessed by Bath Ankylosing Spondylitis Functional Index (BASFI). Clinical activity was evaluated using erythrocyte sedimentation rate, C reactive protein and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Each patient underwent pelvic anteroposterior, anteroposterior and lateral lumbar spine as well as lateral cervical spine x rays; they were scored according to the Bath Ankylosing Spondylitis Spine Radiographic Index, which measures structural damage. RESULTS: Of the 1514 patients screened, 1131 (74.7%) were men. We found significant differences in age at onset of symptoms as well as in the day of inclusion, between the two groups, being lower in men. We also obtained differences in the duration of the disease, which was lower in women. As for the existence of a history of AS among first-degree relatives, family forms were more common among women. The mean BASDAI score was also higher in women, regardless of time since onset of disease. In contrast, the improvement of pain with the use of NSAID's and radiological severity were higher in men, both reaching statistical significance. CONCLUSIONS: Among the Spanish AS patients, there are some differences in the clinical manifestations, even when the time since onset of disease was controlled; we also found radiological differences by gender; men showing more structural damage, while women were more active. These data suggest that the phenotype of AS differs between genders. This can influence the subsequent diagnostic approach and therapeutic decisions.

[Consensus Statement of the Spanish Society of Rheumatology on the management of biologic therapies in spondyloarthritis except for psoriatic arthritis]. / Documento SER de consenso sobre el uso de terapias biológicas en la espondilitis anquilosante y otras espondiloartritis, excepto la artritis psoriásica.

OBJECTIVE: Due to the amount and variability in quality regarding the use of biologic therapy (BT) in patients with spondyloarthritis (SpA), except for psoriatic arthritis (PsA) patients, the Spanish Society of Rheumatology has promoted the generation of recommendations based on the best evidence available. These recommendations should be a reference for rheumatologists and those involved in the treatment of patients with spondyloarthritis (SpA), except for psoriatic arthritis (PsA), who are using, or about to use BT. METHODS: Recommendations were developed following a nominal group methodology and based on systematic reviews. The level of evidence and grade of recommendation were classified according to the model proposed by the Center for Evidence Based Medicine at Oxford. The level of agreement was established through Delphi technique. RESULTS: We have produced recommendations on the use of BT currently available for SpA (but not PsA) in our country. These recommendations include disease assessment, treatment objectives, therapeutic scheme and switching. CONCLUSIONS: We present an update on the SER recommendations for the use of BT in patients with SpA, except for PsA.

[Management of the patient with ankylosing spondylitis (AS) in partial remission with biologic therapy: is it possible to suspend treatment?]. / Manejo del paciente con espondiloartritis anquilosante en remisión parcial con tratamiento biológico: ¿es posible suspender el tratamiento?

The management of patients with AS and a good clinical response to biologic therapy is controversial. The results of the different published papers suggest that the suspension of treatment is not a good therapeutic option in these patients. There is currently no validated definition for clinical remission in patients with AS. A hypothetical definition should include the absence of signs and symptoms of disease in any localization, associated to the lack of progression of the disease and all of this during a period of time long enough to establish its persistence with time. In our experience, those patients presenting an apparent clinical remission, based on the previously established definition, could be considered for temporary treatment suspension, especially if we take into account that the reintroduction of treatment is safe and effective.