One-Year, Efficacy and Safety Open Label Study, with a Single Injection of a New Hyaluronan for Knee OA: The SOYA Trial.

PURPOSE: To assess the efficacy and safety of a single injection of a new formulation of hyaluronic acid (MPS-HA2%) in patients with symptomatic knee osteoarthritis after 12 months' follow-up. PATIENTS AND METHODS: Prospective, single-arm, multicentre, open-label, 12-month follow-up study. Patients with Kellgren-Lawrence (KL) 2-3 and visual analogue scale (VAS) pain scores of ≥40-< 80 mm received a single injection of MPS-HA2%. The primary outcome was the reduction in VAS pain scores from baseline, and the secondary outcomes were the Western Ontario and McMaster (WOMAC) Universities Osteoarthritis Index, the minimum clinically important improvement (MCII), and patient and investigator global assessments (PGA, IGA) measured on 5-point Likert scale. Adverse events were recorded throughout the study for safety purposes. RESULTS: A total of 101 patients (mean age: 68 years; 74% female; and 78% overweight) were included. The mean reduction in pain at 12 months was 37.7%; the total WOMAC score improved by 36.5% and the pain, stiffness and physical function subscores returned improvements of 32.1%, 34.1% and 32.7%, respectively (p=0.0001 with respect to baseline). At 12 months, a statistically significant 62.2% of patients obtained an improvement equal to or greater than the MCII. The mean PGA score at baseline was 2.44 and 1.46 at 12 months (p<0.05), and the mean IGA scores at equivalent timepoints were 2.29 and 1.48 (p<0.05). Fourteen patients received a second injection at the 6-month follow-up visit. Eight patients reported a total of 12 treatment-related adverse events that were local, non-serious and of mild-to-moderate intensity. CONCLUSION: With just a single intra-articular injection, this not controlled trial suggests that MPS-HA2% is effective 12 months after the procedure in most cases. Patient tolerability and safety were both optimal (NCT03852914).

Long-term Follow-up and Optimization of Infliximab in Refractory Uveitis Due to Behçet Disease: National Study of 103 White Patients.

OBJECTIVE: In a large series of White patients with refractory uveitis due to Behçet disease (BD) being treated with infliximab (IFX), we assessed (1) long-term efficacy and safety of IFX, and (2) IFX optimization when ocular remission was achieved. METHODS: Our multicenter study of IFX-treated patients with BD uveitis refractory to conventional immunosuppressant agents treated 103 patients/185 affected eyes with IFX as first biologic therapy in the following intervals: 3-5 mg/kg intravenous at 0, 2, 6, and then every 4-8 weeks. The main outcome variables were analyzed at baseline, first week, first month, sixth month, first year, and second year of IFX therapy. After remission, based on a shared decision between patient and clinician, IFX optimization was performed. Efficacy, safety, and cost of IFX therapy were evaluated. RESULTS: In the whole series (n = 103), main outcome variables showed a rapid and maintained improvement, reaching remission in 78 patients after a mean IFX duration of 31.5 months. Serious adverse events were observed in 9 patients: infusion reactions (n = 4), tuberculosis (n = 1), Mycobacterium avium pneumonia (n = 1), severe oral ulcers (n = 1), palmoplantar psoriasis (n = 1), and colon carcinoma (n = 1). In the optimization subanalysis, the comparative study between optimized and nonoptimized groups showed (1) no differences in clinical characteristics at baseline, (2) similar maintained improvement in most ocular outcomes, (3) lower severe adverse events, and (4) lower mean IFX costs in the optimized group (€4826.52 vs €9854.13 per patient/yr). CONCLUSION: IFX seems to be effective and relatively safe in White patients with refractory BD uveitis. IFX optimization is effective, safe, and cost-effective.

Successful Optimization of Adalimumab Therapy in Refractory Uveitis Due to Behçet's Disease.

PURPOSE: To assess efficacy, safety, and cost-effectiveness of adalimumab (ADA) therapy optimization in a large series of patients with uveitis due to Behçet disease (BD) who achieved remission after the use of this biologic agent. DESIGN: Open-label multicenter study of ADA-treated patients with BD uveitis refractory to conventional immunosuppressants. SUBJECTS: Sixty-five of 74 patients with uveitis due to BD, who achieved remission after a median ADA duration of 6 (range, 3-12) months. ADA was optimized in 23 (35.4%) of them. This biologic agent was maintained at a dose of 40 mg/subcutaneously/2 weeks in the remaining 42 patients. METHODS: After remission, based on a shared decision between the patient and the treating physician, ADA was optimized. When agreement between patient and physician was reached, optimization was performed by prolonging the ADA dosing interval progressively. Comparison between optimized and nonoptimized patients was performed. MAIN OUTCOME MEASURES: Efficacy, safety, and cost-effectiveness in optimized and nonoptimized groups. To determine efficacy, intraocular inflammation (anterior chamber cells, vitritis, and retinal vasculitis), macular thickness, visual acuity, and the sparing effect of glucocorticoids were assessed. RESULTS: No demographic or ocular differences were found at the time of ADA onset between the optimized and the nonoptimized groups. Most ocular outcomes were similar after a mean ± standard deviation follow-up of 34.7±13.3 and 26±21.3 months in the optimized and nonoptimized groups, respectively. However, relevant adverse effects were only seen in the nonoptimized group (lymphoma, pneumonia, severe local reaction at the injection site, and bacteremia by Escherichia coli, 1 each). Moreover, the mean ADA treatment costs were lower in the optimized group than in the nonoptimized group (6101.25 euros/patient/year vs. 12 339.48; P < 0.01). CONCLUSION: ADA optimization in BD uveitis refractory to conventional therapy is effective, safe, and cost-effective.

Anti-TNF-α therapy in patients with refractory uveitis due to Behçet's disease: a 1-year follow-up study of 124 patients.

OBJECTIVE: The aim of this study was to assess the efficacy of anti-TNF-α therapy in refractory uveitis due to Behçet's disease (BD). METHODS: We performed a multicentre study of 124 patients with BD uveitis refractory to conventional treatment including high-dose corticosteroids and at least one standard immunosuppressive agent. Patients were treated for at least 12 months with infliximab (IFX) (3-5 mg/kg at 0, 2 and 6 weeks and then every 4-8 weeks) or adalimumab (ADA) (usually 40 mg every 2 weeks). The main outcome measures were degree of anterior and posterior chamber inflammation, visual acuity, macular thickness and immunosuppression load. RESULTS: Sixty-eight men and 56 women (221 affected eyes) were studied. The mean age was 38.6 years (s.d. 10.4). HLA-B51 was positive in 66.1% of patients and uveitis was bilateral in 78.2%. IFX was the first biologic agent in 77 cases (62%) and ADA was first in 47 (38%). In most cases anti-TNF-α drugs were used in combination with conventional immunosuppressive drugs. At the onset of anti-TNF-α therapy, anterior chamber and vitreous inflammation was observed in 57% and 64.4% of patients, respectively. In both conditions the damage decreased significantly after 1 year. At baseline, 50 patients (80 eyes) had macular thickening [optical coherence tomography (OCT) >250 µm] and 35 (49 eyes) had cystoid macular oedema (OCT>300 µm) that improved from 420 µm (s.d. 119.5) at baseline to 271 µm (s.d. 45.6) at month 12 (P < 0.01). The best-corrected visual acuity and the suppression load also showed significant improvement. After 1 year of follow-up, 67.7% of patients were inactive. Biologic therapy was well tolerated in most cases. CONCLUSION: Anti-TNF-α therapy is effective and relatively safe in refractory BD uveitis.

Efficacy of tocilizumab in conventional treatment-refractory adult-onset Still's disease: multicenter retrospective open-label study of thirty-four patients.

OBJECTIVE: Adult-onset Still's disease (AOSD) is frequently refractory to standard therapy. Tocilizumab (TCZ) has demonstrated efficacy in single cases and in small series of patients with AOSD. The aim of this multicenter study was to assess the efficacy of TCZ in patients with AOSD refractory to conventional treatment. METHODS: This was a retrospective open-label study of TCZ treatment in 34 patients with AOSD who had experienced an inadequate response to corticosteroids and at least 1 standard synthetic immunosuppressive drug and also, in many cases, biologic agents. RESULTS: The mean ± SD age of the patients (8 men and 26 women) was 38.7 ± 16.1 years. The median duration of AOSD before TCZ was initiated was 4.2 years (interquartile range [IQR] 1-9 years). The initial dosages of intravenous TCZ were 8 mg/kg every 4 weeks in 22 patients, 4 mg/kg every 4 weeks in 2 patients, and 8 mg/kg every 2 weeks in 10 patients. TCZ treatment resulted in rapid and maintained improvement in both clinical and laboratory parameters. After 1 year of TCZ therapy, the incidence of joint manifestations had decreased from 97.1% at baseline to 32.4%, the incidence of both cutaneous manifestations and fever had decreased from 58.8% to 5.9%, and the incidence of lymphadenopathy had decreased from 29.4% to 0%. A dramatic reduction in laboratory markers of inflammation, including the C-reactive protein level, the erythrocyte sedimentation rate, and the ferritin level, was achieved. The median dosage of prednisone was also reduced, from 13.8 mg/day (IQR 5-45) at the initiation of TCZ to 2.5 mg/day (IQR 0-30) at 12 months. After a median followup of 19 months (IQR 12-31 months), only 2 patients required permanent discontinuation of TCZ therapy because of severe infections. CONCLUSION: TCZ treatment was associated with rapid and maintained clinical and laboratory improvement in patients with AOSD refractory to standard treatment. However, joint manifestations seem to be more refractory to treatment compared with systemic manifestations.

Valoración de la eficacia del lavado articular no artroscópico en pacientes con artrosis de rodilla / Assessing the efficacy of non-arthroscopic joint lavage in patients with osteoarthritis of the knee

Objetivos El objetivo de este trabajo fue evaluar la eficacia del lavado articular (LA) en pacientes con osteoartrosis de rodilla. Diseño Se realizó un estudio abierto prospectivo en el que se incluyeron 111 pacientes, de los que el 77% eran mujeres. El rango de edad fue de 43 a 81 años y la media de edad de 64 ± 8,7 años. Todos los pacientes tenían diagnóstico de artrosis según los criterios del American College of Rheumatology (ACR), con grado radiológico II y III de la escala radiológica de Kellgren. Los pacientes se aleatorizaron en 2 grupos de tratamiento: a) LA sin antiinflamatorios no esteroideos (AINE) (LA, n=57) y b) AINE solos (AINE, n=54). Las evaluaciones se realizaron de forma basal, al mes, a los 3 meses y a los 6 meses de haberse realizado el tratamiento. Se recogieron variables clínicas y demográficas, así como el índice de WOMAC (Western Ontario and McMaster University). La mejoría de los pacientes se valoró según los criterios de la (Osteoarthritis Research Society International [OARSI] Investigación de la Osteoartritis’). El análisis estadístico incluyó el test de χ2, y el análisis de covarianza (WOMAC basal) con un factor entre sujetos (tratamiento). Las comparaciones post hoc se realizaron con ajuste de Sidak. Resultados El grado de mejoría según los criterios de la OARSI para los pacientes del grupo LA y del grupo AINE fue, respectivamente: 50,9 y 31,5% al mes; 55,4 y 38,9% a los 3 meses, y 63,2 y 64,8% a los 6 meses. Los pacientes en ambos grupos mejoraron desde el primer mes (p=0,038). Al final de los 6 meses del seguimiento, el WOMAC había descendido significativamente en ambos grupos (p=0,000), sin que hubiera diferencias significativas entre ellos. Conclusiones A los 6 meses del tratamiento, el LA es tan eficaz como los AINE en pacientes con gonartrosis, por lo que es una alternativa terapeútica eficaz en los pacientes en los que los AINE están contraindicados (AU)

Objective To evaluate the efficacy of joint lavage in patients with osteoarthritis of the knee. Design We conducted an open prospective study involving 111 patients of whom 77% were females. The patients’ age range was 43–81 years and the average age 64±8.7 years. All patients had gonarthrosis as diagnosed according to the (ACR) American College of Rheumatology criteria (Kellgren radiographic grades II and III). Patients were randomly distributed between two treatment groups: a) Joint lavage without non-steroidal anti-inflammatory drugs (NAJL, n=57), and b) non-steroidal anti-inflammatory drugs alone (NSAIDs, n=54). Evaluations were done at baseline and one, three, and six months after enrollment. Clinical and demographic variables, and WOMAC index scores, were recorded and patient improvement was determined by following the OARSI guidelines. Statistical analyses included chi-square, analysis of covariance (baseline WOMAC) with one between-subject factor (treatment). Post-hoc comparisons were made with Sidak's adjustment. Results The respective improvement rates as measured by the OARSI index for the patients in the JL and NSAIDs groups were 50.9 and 31.5% at 1 month; 55.4 and 38.9% at three months; and 63.2 and 64.8% at six months. The patients in both groups were seen to improve from the first month (P=.038). At the end of the six-month follow-up period, the WOMAC score had decreased significantly in both groups (P=.000), with no significant differences between them. Conclusions Six months after treatment, joint lavage proved as effective as NSAIDs in patients with gonarthrosis, so it constitutes an effective therapeutic choice in those cases where NSAIDs are contraindicated (AU)

[Assessing the efficacy of non-arthroscopic joint lavage in patients with osteoarthritis of the knee]. / Valoración de la eficacia del lavado articular no artroscópico en pacientes con artrosis de rodilla.

OBJECTIVE: To evaluate the efficacy of joint lavage in patients with osteoarthritis of the knee. DESIGN: We conducted an open prospective study involving 111 patients of whom 77% were females. The patients' age range was 43-81 years and the average age 64±8.7 years. All patients had gonarthrosis as diagnosed according to the (ACR) American College of Rheumatology criteria (Kellgren radiographic grades II and III). Patients were randomly distributed between two treatment groups: a) Joint lavage without non-steroidal anti-inflammatory drugs (NAJL, n=57), and b) non-steroidal anti-inflammatory drugs alone (NSAIDs, n=54). Evaluations were done at baseline and one, three, and six months after enrollment. Clinical and demographic variables, and WOMAC index scores, were recorded and patient improvement was determined by following the OARSI guidelines. Statistical analyses included chi-square, analysis of covariance (baseline WOMAC) with one between-subject factor (treatment). Post-hoc comparisons were made with Sidak's adjustment. RESULTS: The respective improvement rates as measured by the OARSI index for the patients in the JL and NSAIDs groups were 50.9 and 31.5% at 1 month; 55.4 and 38.9% at three months; and 63.2 and 64.8% at six months. The patients in both groups were seen to improve from the first month (P=.038). At the end of the six-month follow-up period, the WOMAC score had decreased significantly in both groups (P=.000), with no significant differences between them. CONCLUSIONS: Six months after treatment, joint lavage proved as effective as NSAIDs in patients with gonarthrosis, so it constitutes an effective therapeutic choice in those cases where NSAIDs are contraindicated.