Similar efficacy, safety and immunogenicity of adalimumab biosimilar BI 695501 and Humira reference product in patients with moderately to severely active rheumatoid arthritis: results from the phase III randomised VOLTAIRE-RA equivalence study.

OBJECTIVE: To demonstrate clinical equivalence of adalimumab biosimilar candidate BI 695501 with Humira. METHODS: Patients with active rheumatoid arthritis on stable methotrexate were randomised to BI 695501 or Humira in a double-blind, parallel-group, equivalence study. At week 24, patients were rerandomised to continue BI 695501 or Humira, or switch from Humira to BI 695501. The coprimary endpoints were the percentage of patients achieving the American College of Rheumatology 20% response criteria (ACR20) at weeks 12 and 24. Further efficacy and safety endpoints and immunogenicity were assessed up to week 58. RESULTS: 645 patients were randomised. At week 12, 67.0% and 61.1% (90% CI -0.9 to 12.7) of patients receiving BI 695501 (n=324) and Humira (n=321), respectively, achieved ACR20; at week 24 the corresponding values were 69.0% and 64.5% (95% CI -3.4 to 12.5). These differences were within prespecified margins (week 12: 90% CI (-12% to 15%); week 24: 95% CI (-15% to 15%)), demonstrating therapeutic bioequivalence. 593 patients were rerandomised at week 24. Up to week 48, mean change from baseline in Disease Activity Score 28-erythrocyte sedimentation rate and ACR20/ACR50/ACR70 response rates were similar across the switched (n=147), continuous BI 695501 (n=298) and continuous Humira (n=148) groups. Similar immunogenicity (antidrug antibodies (ADAs), ADA titres and neutralising antibodies) was seen between BI 695501 and Humira (to week 24) and across rerandomised groups (to week 48). Safety and tolerability profiles were similar between groups. CONCLUSIONS: BI 695501 demonstrated similar efficacy, safety and immunogenicity to Humira; switch from Humira to BI 695501 had no impact on efficacy, safety and immunogenicity. TRIAL REGISTRATION NUMBER: NCT02137226, Results.

Clinical utility of the ASDAS index in comparison with BASDAI in patients with ankylosing spondylitis (Axis Study).

The objective of the study was to study the clinical utility of the Ankylosing Spondylitis Disease Activity Score (ASDAS) for the assessment of disease activity in ankylosing spondylitis (AS) patients, compared to the Bath Ankylosing Spondylitis Activity Index (BASDAI). This was a prospective longitudinal observational study in patients with AS (NY-modified criteria) from 23 Spanish centers. Physical and analytical data; global, lumbar, and nocturnal pain; ASDAS, BASDAI and minimally acceptable clinical status (PASS) were collected. Psychometric characteristics of both indexes were analyzed: construct validity (convergent and divergent), discriminant capacity, criterion validity (global physician and patient assessment), and sensitivity to change. The study involved 127 patients (19.7% attrition). Both BASDAI and ASDAS showed a higher correlation with patient's global assessment (r = 0.76 and 0.70, respectively) than with physician's global assessment (r = 0.67 and 0.57). Both scores allowed discriminating patients with an acceptable clinical status, although BASDAI to a greater extent than ASDAS (Cohen δ 1.72 vs 0.88 for the medical PASS). Both scores showed sensitivity to change in patients who changed from an unacceptable symptomatic state to acceptable according to PASS criteria (physician and patient) and by BASDAI 50 response criteria (Cohen δ > 0.80). BASDAI showed better criterion validity than ASDAS, both for the patient PASS (AUC 0.85 vs 0.79) and for the physician's (AUC 0.90 vs 0.79). ASDAS shows adequate performance for disease activity in patients with AS; however, in this study, its psychometric properties do not present advantages over BASDAI in terms of criterion validity, sensitivity to change or discriminative capacity; replacement of BASDAI by ASDAS is not supported by the data.

Quality of care standards for nursing clinics in rheumatology.

BACKGROUND: Nursing clinics in rheumatology (NCR) are organizational models in the field of nursing care. There are various NCR models, but there is no consensus on its operational definition. Our objective is to develop quality standards to define and characterize a NCR. METHOD: Two-round Delphi method. The panel consisted of 67 experts: Rheumatologists and nurses of the nursing working group of the Spanish Society of Rheumatology (SSR). The Delphi questionnaire was developed after a literature and experience review from previous SSR projects. The questionnaire consists of 7 sections: general considerations, standards of structure, process, treatment and monitoring, health education, training and research and quality of care. Each item was scored from 1 (least important) to 9 (most important) or by assigning a number (e.g., waiting days). The degree of agreement among the experts was categorized according to the coefficient of variation (CoV) between very high (CoV≤25%) and very low (CoV>100%). RESULTS: The second round questionnaire (182 items) was answered by 46 panelists (34 rheumatologists and 12 nurses). A very important agreement was reached on the general standards of structure, process, treatment and monitoring, health education and quality of care. Less agreement was observed on standards related to training time, number of recommended nurses' research projects and publications. CONCLUSION: The standards developed in this study would be useful for establishing desirable quality standards of structure and process, and criteria for clinical work, research and teaching that can be used to develop and evaluate the NCRs.

[2011 Up-date of the consensus statement of the Spanish Society of Rheumatology on osteoporosis]. / Actualización 2011 del consenso Sociedad Española de Reumatología de osteoporosis.

OBJECTIVE: Due to increasing improvement in the diagnosis, evaluation and management of osteoporosis and the development of new tools and drugs, the Spanish Society of Rheumatology (SER) has promoted the development of recommendations based on the best evidence available. These recommendations should be a reference to rheumatologists and other health professionals involved in the treatment of patients with osteoporosis. METHODS: Recommendations were developed following a nominal group methodology and based on a systematic review. The level of evidence and degree 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. Evidence from previous consensus and available clinical guidelines was used. RESULTS: We have produced recommendations on diagnosis, evaluation and management of osteoporosis. These recommendations include the glucocorticoid-induced osteoporosis, premenopausal and male osteoporosis. CONCLUSIONS: We present the SER recommendations related to the biologic therapy risk management.

[Opioid use in osteoarthritis: From guidelines to clinical care]. / Opioides en la artrosis. De las guías a la práctica clínica.

Three treatment guidelines for the treatment of knee and hip osteoarthritis (OA) which pick up the aspects of treatment supported by evidence have been published. Opioid drugs have an important role in symptomatic treatment. The guidelines, the effectiveness, and the safety of opioid analgesics in osteoarthritis, as well as its implications in clinical practice are reviewed. Tramadol is the opioid with the biggest evidence of effectiveness and safety, besides being the most used in clinical practice. Strong opioids (transdermic brupenorphine or fentanyl, oxycodone, and morphine) can be used in severe pain that does not respond to other treatments. Opioids can be used in patients that have moderate or severe pain or in those with inadequate response or intolerance to NSAID's. The opioids also have a sedative effect that facilitates sleep and can improve functional limitations and anxiety. The side effects are frequent; they usually appear at the beginning of treatment and are rarely severe, but frequently force to stop treatment.

Tumor necrosis factor alpha drugs in rheumatoid arthritis: systematic review and metaanalysis of efficacy and safety.

BACKGROUND: To analyse available evidence on the efficacy and safety of anti-TNFalpha drugs (infliximab, etanercept and adalimumab) for treating rheumatoid arthritis (RA). METHODS: We searched systematically for randomised controlled clinical trials on treatment of RA with anti-TNFalpha drugs, followed by a systematic review with metaanalysis. Trials were searched from MEDLINE, EMBASE and Cochrane Library databases. The American College of Rheumatology (ACR) efficacy response criteria were used. Safety parameters provided by the trials were also assessed. Positive and undesired effects were estimated using combined relative risks (RR), number needed to treat (NNT) and number needed to harm (NNH). Heterogeneity was evaluated by Cochrane's Q and I2 statistics. RESULTS: Thirteen trials (7087 patients) met the inclusion criteria. The combined RR to achieve a therapeutic response to treatment with recommended doses of any anti-TNFalpha drug was 1.81 (95% CI 1.43-2.29) with a NNT of 5 (5-6) for ACR20. NNT for ACR50 [5 (5-6)] and ACR70 [7 (7-9)] were similar. Overall therapeutic effects were also similar regardless of the specific anti-TNFalpha drug used and when higher than recommended doses were administered. However, lower than recommended doses elicited low ACR70 responses (NNT 15). Comparison of anti-TNFalpha drugs plus methotrexate (MTX) with MTX alone in patients with insufficient prior responses to MTX showed NNT values of 3 for ACR20, 4 for ACR50 and 8 for ACR70. Comparison of anti-TNFalpha drugs with placebo showed a similar pattern. Comparisons of anti-TNFalpha drugs plus MTX with MTX alone in patients with no previous resistance to MTX showed somewhat lower effects. Etanercept and adalimumab administered as monotherapy showed effects similar to those of MTX. Side effects were more common among patients receiving anti-TNFalpha drugs than controls (overall combined NNH 27). Patients receiving infliximab were more likely to drop out because of side effects (NNH 24) and to suffer severe side effects (NNH 31), infections (NNH 10) and infusion reactions (NNH 9). Patients receiving adalimumab were also more likely to drop out because of side effects (NNH 47) and to suffer injection site reactions (NNH 22). Patients receiving etanercept were less likely to drop out because of side effects (NNH for control versus etanercept 26) but more likely to experience injection site reactions (NNH 5). CONCLUSION: Anti-TNFalpha drugs are effective in RA patients, with apparently similar results irrespective of the drug administered. Doses other than those recommended are also beneficial. The main factor influencing therapeutic efficacy is the prior response to DMARD treatment. The effect of treatment with etanercept or adalimumab does not differ from that obtained with MTX. The published safety profile for etanercept is superior but the fact that no patients are treated with higher than recommended doses requires explanation.

[Infections in Patients With Rheumatoid Arthritis Undergoing Anti-TNFα Drug Therapy]. / Infecciones en pacientes con artritis reumatoide en tratamiento con fármacos anti-TNFα

Infections are more frequent in patients with rheumatoid arthritis (RA). The capacity of the anti-TNF drugs (infliximab, etanercept, and adalimumab) to increase the risk of infections has been a motive of discussion during the past years. Only in two of the trials that have allowed the marketing of the infliximab and adalimumab more serious infections were observed. TB was not observed in the trials. Nevertheless, later they have been published not controlled studies that show infections and TB in patients with RA that receive anti-TNFα drugs. The disagreement between the trials and the not controlled studies has been the motive of the accomplishment of metaanalysis which study the frequency of infections in patients with RA that receive anti-TNFα drugs. The three metaanalysis published show an increase of the risk of infections in patients with AR in treatment with infliximab and with adalimumab, specially when they administer high doses. This risk does not seem to increase with etanercept, probably due to the fact that doses superior to the recommended ones have not been used in the analyzed trials. Increased risk of infections was not detected in the trials, but the metaanalysis increases the statistical power and allow demonstrating increased risk of infections. A causal relation exists between the administration of anti-TNFα and the development of infections, fulfilling all the criteria of causality.

[A Case of Cutaneous Tuberculosis is Simulating Paraneoplastic Vasculitis]. / Un caso de tuberculosis cutánea semejante a una vasculitis paraneoplásica.

We present the case of a patient with type T non-Hodgkin lymphoma, in clinical remission after treatment with chemo and radiotherapy, who was hospitalized due to hemorrhagic and necrotic skin lesions on his right hand and a clinical suspicion of paraneoplasic vasculitis. Nonetheless, study of the patient and complementary testing led to the diagnosis of disseminated tuberculosis with skin and lung involvement (cutaneous milliary tuberculosis). Anti-tuberculosis treatment was initiated with a satisfactory resolution of symptoms and signs.

[Asistance quality standards in rheumatology]. / Estándares de calidad asistencial en reumatología.

OBJECTIVE: To developed standards for quality of care and processing times in rheumatology. MATERIALS AND METHODS: After a systematic review of the literature, a working group of 10 rheumatologists and 2 methodologists selected 164 indicators of quality of care and processing times. A panel of 65 experts rated the indicators following a Delphi methodology. RESULTS: Among the most important of the 164 standards obtained were: maximum number of inhabitants per rheumatologist (40,000-50,000); minimum number of rheumatologists in a Rheumatology Unit (3); duration of the first visit (30 minutes) and successive visits (19 minutes), ratio of successive/first visits (3.2); a rheumatologist should receive no more than 5 first visits/day and no more than 11 successive visits/day, and should spend no more than 5 hours on patients visits/day nor more than 4 days/week; the maximum waiting time for first visits should not exceed 4 weeks; the time needed to visit hospitalised patients (43 minutes on admission, 17 minutes for daily visit and 40 minutes at discharge); and time to carry out some of the most frequent procedures in rheumatology (12 minutes for arthrocentesis and infiltrations and 17 minutes for synovial fluid analysis). CONCLUSIONS: This study establishes basic standards for quality of care, organisation and process times. It is a useful tool for organizing a Rheumatology Unit which can facilitate dialogue with health administrators and help improve the quality of rheumatology care.