Standardized Follow-up of Patients with Symptomatic Knee Osteoarthritis Treated with a Single Intra-articular Injection of a Combination of Cross-Linked Hyaluronic Acid and Mannitol

Objectives The objective of this study is to obtain pilot data from daily practice conditions of a viscosupplement made of a cross-linked high-molecular-weight hyaluronic acid (HA) combined with mannitol in patients with knee osteoarthritis (KOA). Methods The data of 40 consecutive patients, 29 women and 11 men, who were prospectively followed up for 6 months, using a standardized procedure, were retrospectively analyzed. All patients have received a single intra-articular injection of H Anox-M-XL (4.4 mL), viscosupplement made of a cross-linked HA (16 mg/mL) + mannitol (35 mg/mL), in the target knee. The primary outcome was safety. The secondary end points included 3- and 6-month change in the WOMAC pain (0–50) and WOMAC total (0–240) and patient's global assessment (PGA). Patient's self-assessment of treatment efficacy (0–3) and analgesic consumption were obtained at months 3 and 6. An intent-to-treat analysis was performed. Results Mean (SD) age was 60.7 (13.9) years, and mean BMI was 28.6 (5.0). Kellgren–Lawrence radiological grade was I/II and III/IV in 13 and 27 of the subjects, respectively. The average WOMAC pain and WOMAC total scores at baseline were 21.5 (9.8) and 89.9 (42.8), respectively. Thirty-nine patients completed the follow-up. HAnox-M-XL was well tolerated; two patients experienced knee pain after injection, which resolved within three days. No treatment-related severe adverse event was reported. Mean (SD) variations in WOMAC pain and WOMAC total scores were –8.2 (8.9) and –38.4 (35.6), respectively, at month 6 ( P = 0.001). PGA decreased from 5.5 (2.0) to 3.0 (2.2) ( P = 0.006). Efficacy was rated as good or very good in 76.9% of the cases. Most of the regular analgesics users decreased their consumption. Conclusion Treatment with one injection of 4.4 mL HAnox-M-XL is effective to alleviate KOA symptoms over six months, without safety concern. Controlled trials are needed to confirm these pilot data

Onset or exacerbation of cutaneous psoriasis during TNFalpha antagonist therapy.

International audienceThe widespread use of TNFalpha antagonists in recent years has led to the recognition of paradoxical adverse effects, defined as the onset or exacerbation of disorders that are usually improved by TNFalpha antagonists. Cutaneous psoriasis is an example, of which several cases have been reported. OBJECTIVE: To identify cases of psoriasis onset or exacerbation during TNFalpha antagonist therapy and to look for potential predictive factors. METHODS: We retrospectively reviewed cases of psoriasis onset or exacerbation during TNFalpha antagonist therapy. For each case we recorded the following data: age, sex, underlying disease, nature of the TNFalpha antagonist, effectiveness in improving the underlying disease, history of psoriasis in the patient or family, time to psoriasis development, type of psoriasis (confirmed by an experienced dermatologist), concomitant treatments, whether the TNFalpha antagonist was stopped or continued, and the outcome of the psoriasis. These data were compared to those in the literature. RESULTS: We identified 12 patients, six men and six women, with a mean age of 45.5 years. The TNFalpha antagonist was adalimumab in four patients, etanercept in six patients, and infliximab in two patients. The underlying disease was ankylosing spondylitis in six cases, rheumatoid arthritis in four, and psoriatic arthritis in two. Mean time from treatment initiation to psoriasis was 4.1 months (range, 1-15 months). A previous history of psoriasis in the patient was noted in six cases, including four of the six patients taking etanercept. TNFalpha antagonist therapy was effective on the underlying disease in 11 of the 12 patients. The drug was discontinued in five patients, of whom four experienced resolution of their psoriasis. In the remaining seven patients, the drug was continued and the skin lesions remained unchanged. Most of the patients had psoriasis vulgaris (plaque psoriasis); palmoplantar pustulosis was a feature in five patients. DISCUSSION: Over 40 cases of psoriasis onset or exacerbation during TNFalpha antagonist therapy have been reported in the literature. The prevalence of this adverse effect has been estimated at 1.5-5% of patients taking TNFalpha antagonists. The findings from our case series are consistent with data in the literature. Psoriasis is a class effect that has been reported with all the currently available TNFalpha antagonists. The skin lesions develop within the first few months of therapy. Patients with a wide range of underlying diseases can be affected. Palmoplantar pustulosis is a common feature. A previous history of psoriasis seems more common in patients who experience psoriasis onset or exacerbation during etanercept therapy (four of six patients in our study and 55% in the literature); thus, previous psoriasis may be a risk factor for psoriasis exacerbation during etanercept therapy

Safety of rituximab in rheumatoid arthritis patients with a history of severe or recurrent bacterial infection: observational study of 30 cases in everyday practice.

International audienceOBJECTIVES: To report our experience with rituximab therapy in patients with rheumatoid arthritis (RA) and a history of severe or recurrent bacterial infections. PATIENTS AND METHODS: Retrospective observational study in five rheumatology departments experienced in the use of biotherapies. Patients were included if they had RA and a history of severe or recurrent bacterial infection (requiring admission and/or intravenous antimicrobial therapy) that contraindicated the introduction or continuation of TNFalpha antagonist therapy. RESULTS: Of 161 RA patients given rituximab in the five study centers, 30 met the inclusion criteria, 23 females and seven males with a mean age of 58.4+/-11.8 years and a mean disease duration of 11.4+/-13.9 years. Among them, 22 had rheumatoid factors and 21 had received TNFalpha antagonist therapy (one agent in 15 patients, two in five patients and three in one patient). Prior infections were as follows: septicemia, n=2; lower respiratory tract infection or lung abscess, n=12; prosthesis infection, n=3; septic arthritis, n=3; endocarditis, n=1; pyelonephritis, n=2; osteitis, n=4; and various skin infections (erysipelas, cellulitis or skin abscess), n=6. Of these 33 infections, 21 occurred during TNFalpha antagonist therapy. During rituximab therapy, all patients received concomitant glucocorticoid therapy (mean dosage, 12+/-7.9 mg/day). The number of rituximab cycles was one in 13 patients, two in seven patients and three or more in 10 patients. Mean time from the single or last serious infection and the first rituximab infusion was 20.1+/-18.7 months. Mean follow-up since the first rituximab infusion was 19.3+/-7.4 months. During follow-up, six (20%) patients experienced one infection each. Immunoglobulin levels after rituximab therapy were within the normal range. CONCLUSION: Rituximab therapy was well tolerated in 24 (80%) of 30 patients with RA and a history of severe or recurrent bacterial infection. In everyday practice, rituximab therapy seems safe with regard to the recurrence of infectious episodes. However, longer follow-ups are needed

Early decrease of serum biomarkers of type II collagen degradation (Coll2-1) and joint inflammation (Coll2-1 NO(2) ) by hyaluronic acid intra-articular injections in patients with knee osteoarthritis: a research study part of the Biovisco study.

To measure the evolution of the serum levels of specific Osteoarthritis (OA) biomarker, Coll2-1 and Coll2-1 NO(2) in knee osteoarthritic patients after viscosupplementation (VS). Fifty-one patients with unilateral symptomatic knee were recruited for this prospective open label study. They received three intra-articular injections of 2 ml of hyaluronic acid (Hylan GF-20) and were followed for 3 months. Walking pain was evaluated and serum samples were taken at each visit. Coll2-1 and Coll2-1 NO(2) were measured in the serum using specific immunoassays. Variations over time of each parameter and predictive factor of response were studied. Forty-five patients were analyzed. The serum concentrations of Coll2-1 and Coll2-1 NO(2) were significantly higher in KL III/IV patients compared to KL I/II patients at baseline and decreased systematically over time after VS. Its effect was ever more pronounced in patients with KL III/IV. The serum concentration of Coll2-1 was significantly lower at baseline in responders than in non-responders. This study suggests a rapid slowdown of type II collagen degradation and joint inflammation after VS with Hylan G-20 and gives additional information for the validation of accurate biomarkers for OA. The serum level of Coll2-1 appeared to be a predictive factor for response to treatment

EFFECTS OF INTRA-ARTICULAR INJECTIONS OF HYLAN GF-20 ON SERUM AND URINE BIOMARKERS IN PATIENTS WITH KNEE OSTEOARTHRITIS: THE BIOVISCO STUDY

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