Long-term structural and symptomatic effects of intra-articular sprifermin in patients with knee osteoarthritis: 5-year results from the FORWARD study

ObjectiveThe FORWARD (FGF-18 Osteoarthritis Randomized Trial with Administration of Repeated Doses) trial assessed efficacy and safety of the potential disease-modifying osteoarthritis drug (DMOAD) sprifermin in patients with knee osteoarthritis. Here, we report 5-year efficacy and safety results.MethodsPatients were randomised to intra-articular sprifermin 100 µg or 30 µg every 6 months (q6mo) or 12 months, or placebo, for 18 months. The primary analysis was at year 2, with follow-up at years 3, 4 and 5. Additional post hoc exploratory analyses were conducted in patients with baseline minimum radiographic joint space width 1.5–3.5 mm and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain 40–90, a subgroup at risk (SAR) of progression.Results378 (69%) patients completed the 5-year follow-up. A significant dose-response in total femorotibial joint cartilage thickness with sprifermin (trend test, p<0.001) and a 0.05 mm mean difference with sprifermin 100 µg q6mo versus placebo (95% CI 0.00 to 0.10; p=0.015) were sustained to year 5. WOMAC pain scores improved ~50% from baseline in all groups. No patient in the 100 µg q6mo group had replacement of the treated knee. 96%–98% of patients receiving sprifermin and 98% placebo reported adverse events, most were mild or moderate and deemed unrelated to treatment. Adverse event-related study withdrawals were <10%. Differentiation in WOMAC pain between sprifermin 100 µg q6mo and placebo in the SAR (n=161) at year 3 was maintained to year 5 (−10.08; 95% CI −25.68 to 5.53).ConclusionIn the longest DMOAD trial reported to date, sprifermin maintained long-term structural modification of articular cartilage over 3.5 years post-treatment. Potential translation to clinical benefit was observed in the SAR.Trial registration numberNCT01919164

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Changes in Knee Joint Space Width in Treatment with a New Hyaluronic-Based Hydrogel

Acta Medica Marisiensis ◽

10.1515/amma-2017-0017 ◽

2017 ◽

Vol 63 (3) ◽

pp. 125-128

Author(s):

Octav Marius Russu ◽

Andrei Marian Feier ◽

Tudor Sorin Pop ◽

Marcela Todoran ◽

István Gergely

Keyword(s):

Hyaluronic Acid ◽

Knee Joint ◽

Knee Osteoarthritis ◽

Joint Space Narrowing ◽

Joint Space Width ◽

Joint Space ◽

One Year ◽

A Minor ◽

Space Width

AbstractObjective: Our purpose was to assess the effect of a new hyaluronic acid-based (Hymovis®) injections on joint space width narrowing in patients diagnosed with knee osteoarthritis.Methods: A prospective clinical trial was conducted in the Department of Orthopedics and Traumatology II from the Clinical County Hospital, Tîrgu Mureș, Romania. Thirty-five patients diagnosed with idiopathic knee osteoarthritis received two intraarticular injections with hyaluronic acid-based hydrogel (24 mg of hyaluronic acid/3 ml) at one-week interval. Anteroposterior radiographs were obtained before the injections, at six and twelve months after. Minimum joint space width was measured by two senior orthopaedics surgeons at each follow up. Each radiograph was measured again by the same evaluators two weeks apart.Results: Thirty-one patients were present at the final follow-up. A minor reduction in mean weight was noticed (from 82.2 kg ± 16.2 kg to 80.9 kg ± 16.0, p > 0.398) without any correlation with joint space width narrowing. There were no major changes at the first follow up (6 months) regarding joint space narrowing. A reduction in joint space width was observed however at 12 months varying from 4.4 mm (SD ± 1.64, range 1.8-7.1) at the first assessment to 4.3 mm (SD ± 1.26, range 0.0-6.8) at the final follow-up but with no statistical difference (p=0.237).Conclusion: No significant modification in joint space width at the final follow-up secondarily proved that two injections of Hymovis® may slow down narrowing in the knee joint space over a one-year period.

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One-year efficacy and safety of single or one to three weekly injections of hylan G-F 20 for knee osteoarthritis: a systematic literature review and meta-analysis

Clinical Rheumatology ◽

10.1007/s10067-020-05477-7 ◽

2020 ◽

Author(s):

Orazio De Lucia ◽

Joerg Jerosch ◽

Sophie Yoon ◽

Tobias Sayre ◽

Wilson Ngai ◽

...

Keyword(s):

Knee Osteoarthritis ◽

Physical Function ◽

Treatment Options ◽

Womac Pain ◽

Efficacy And Safety ◽

Knee Oa ◽

Randomized Studies ◽

Sf 36 ◽

Meta Analyses

Abstract The aim of this study was to evaluate the long-term efficacy and safety of single or 1–3 weekly injections of hylan G-F 20 at 1 year following the first injection for knee osteoarthritis (OA). Searches were conducted in PubMed/MEDLINE, Embase, and CENTRAL and included relevant conference proceedings (January 1, 1995–August 17, 2020). Randomized controlled trials (RCTs), non-randomized trials, and observational studies investigating 1-year efficacy and safety of 1–3 weekly injections or single hylan G-F 20 injection for knee OA were included. Primary outcomes were WOMAC pain, physical function, and stiffness. Meta-analyses of RCTs and non-randomized studies were conducted separately. Our search identified 24 eligible studies. Hylan G-F 20, in the meta-analyses of RCTs, showed statistically significant improvement in WOMAC pain (SMCC − 0.98, 95% CI − 1.50, − 0.46), physical function (SMCC − 1.05, 95% CI − 1.28, − 0.83), and stiffness (SMCC − 1.07, 95% CI −1.28, −0.86). Improvement was also seen for VAS pain, SF-36 MCS (mental component summary), and SF-36 PCS (physical component summary). Analyses of non-randomized studies showed similar efficacy estimates. There were no significant differences in efficacy based on injection schedule, nor between RCT and non-randomized studies. Rates of adverse events (AEs) were low for most types of AEs. Hylan G-F 20 (either as single or 1–3 weekly injections) showed improvement in 1-year efficacy outcomes in comparison to baseline and was generally well tolerated. While further research will inform the medical field regarding viscosupplementation treatment options for knee OA, these findings show that hylan G-F 20 at both frequencies/dosages are efficacious and generally well tolerated for long-term use.

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SAT0572 CONSTRUCTIVE VALIDITY OF MUSKULOSKELETAL ULTRASOUND MEASUREMENT OF CARTILAGE THICKNESS IN PATIENTS WITH KNEE OSTEOARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.3049 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1244.2-1245

Author(s):

Z. Velickovic ◽

S. Janjic ◽

V. Bajec ◽

B. Stojic ◽

T. Zivanovic Radnic ◽

...

Keyword(s):

Knee Osteoarthritis ◽

Joint Space Width ◽

Cost Effective ◽

Joint Space ◽

Pain Scale ◽

Cartilage Thickness ◽

Altman Analysis ◽

Bland Altman Analysis ◽

Femoral Cartilage Thickness

Background:Cartilage thickness is one important measure in describing both OA development and progression. Based on current knowledge, conventional radiography (CR) and magnetic resonance imaging (MRI) have not been demonstrated to be superior over one another. Because of disadvantages of MRI and CR neither can be use in routine daily clinical practice for follow up of OA patients. Diagnostic ultrasound assessment (US) of cartilage thickness offers an alternative measure as a clinically available and more cost-effective source of knee articular cartilage imaging.Objectives:Our objective was to determine the relationship between US and CR measures of femoral cartilage thickness in patients with knee osteoarthritis because systematic feature- and site-specific cross-comparison between this two methods is still missing in the current literature.Methods:120 patients with knee osteoarthritis (240 knees) are recruited for this study. The joint space width (JSW) and Kellgren and Lawrence (K&L) grade were measured using weight-bearing anteroposterior 30° knee semi-flexion knee radiography (with inclusion criteria K&L grade 1-4). Femoral cartilage thickness was measured three times in supine position and with a suprapatellar transverse scan with the knee in maximal flexion at the lateral condyle (LC), medial condyle (MC) and intercondylar notch (IN) by one rheumatologist and arithmetic mean is taken. Pain and functionality are measured with VAS pain scale, Womac, Lysholm and SF 36 score. The agreement between two methods was evaluated with Bland-Altman analysis.Results:We found a statistically significant low level of rank correlation between CR and US measurements of mean cartilage thickness; ρ (rho) values between modalities were low (0.263 and 0.273 depending on side (right/left), p=0.005 and p=0.007 respectively). In Bland – Altman analysis, US measurement showed bad agreement with CR. Presence or absence of US features of OA (effusion, synovial hypertrophy, osteophytes and popliteal cysts) didn’t influence on cartilage thickness assessed by US (p>0.05). For US assessment, we found correlation only between cartilage thickness and VAS pain scale (ρ (rho) -0.281, p=0.004). We didn’t found any statistically significant correlation between CR thickness measures and pain/functionality/HRQoL scores (p>0.05).Conclusion:These results suggest that ultrasound may be a useful clinical tool to assess relative cartilage thickness. However, the absolute validity of the ultrasound measure is called into question due to the larger CR-based thickness measures and low level of agreement according to Bland-Altman analysis. The use of ultrasound as a complementary imaging tool along with CR may enable more accurate and cost-effective detection, prognosis and follow-up of knee osteoarthritis in routine clinical practice.References:[1]Mehta N, Duryea J, Badger GJ, et al. Comparison of 2 Radiographic Techniques for Measurement of Tibiofemoral Joint Space Width.Orthop J Sports Med. 2017;5:2325967117728675.[2]Schmitz RJ, Wang HM, Polprasert DR, Kraft RA, Pietrosimone BG. Evaluation of knee cartilage thickness: A comparison between ultrasound and magnetic resonance imaging methods.Knee. 2017;24:217–223.[3]Podlipská J, Guermazi A, Lehenkari P, et al. Comparison of Diagnostic Performance of Semi-Quantitative Knee Ultrasound and Knee Radiography with MRI: Oulu Knee Osteoarthritis Study.Sci Rep. 2016;6:22365[4]Razek AA, El-Basyouni SR. Ultrasound of knee osteoarthritis: interobserver agreement and correlation with Western Ontario and McMaster Universities Osteoarthritis.Clin Rheumatol. 2016;35:997–1001.[5]Oo WM, Bo MT. Role of Ultrasonography in Knee Osteoarthritis.J Clin Rheumatol. 2016;22:324–329.Disclosure of Interests:None declared

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Long‐term efficacy and safety of risankizumab for the treatment of moderate‐to‐severe plaque psoriasis: interim analysis of the LIMMitless open‐label extension trial beyond 3 years of follow‐up

British Journal of Dermatology ◽

10.1111/bjd.20595 ◽

2021 ◽

Author(s):

K.A. Papp ◽

M.G. Lebwohl ◽

L. Puig ◽

M. Ohtsuki ◽

S. Beissert ◽

...

Keyword(s):

Plaque Psoriasis ◽

Interim Analysis ◽

Efficacy And Safety ◽

Open Label ◽

Severe Plaque Psoriasis ◽

Term Efficacy ◽

Open Label Extension ◽

Extension Trial

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Long-term outcomes after corrective cartilaginous joint resection based on arthrographic findings of duplicated thumbs

Journal of Hand Surgery (European Volume) ◽

10.1177/1753193421994780 ◽

2021 ◽

Vol 46 (4) ◽

pp. 367-372

Author(s):

Kousuke Iba ◽

Akira Saito ◽

Megumi Hanaka ◽

Toshihiko Yamashita

Keyword(s):

Growth Period ◽

Joint Space ◽

Type Ii ◽

Scoring Method ◽

Joint Congruency ◽

Thumb Duplication ◽

Age At Surgery ◽

Joint Connection

We report greater than 10-year outcomes in duplicated thumbs following corrective cartilaginous resection during the growth period. We have undertaken corrective resection of cartilaginous joint connections based on intraoperative arthrographic findings to reconstruct favourable alignment in six Wassel Type II and IV thumb duplication in six patients. The age at surgery was 13 months (range 10–15), and the average post-surgical follow-up was 134 months (range 120–160). We observed five excellent and one good outcome using the Japanese Society for Surgery of the Hand scoring method. Favourable joint congruency and alignment were preserved, and no growth plate arrest or joint space narrowing was present more than 10 years after surgery. We conclude that corrective resection of the cartilaginous joint based on intraoperative arthrographic findings has long-term reliability for duplicated thumbs, especially those of Wassel Type II and IV, which have a cartilaginous joint connection. Levels of evidence: IV

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Long-term outcomes after endoscopic retrograde pancreatic drainage for symptomatic pancreaticojejunal anastomotic stenosis

Scientific Reports ◽

10.1038/s41598-021-84024-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Akihiko Kida ◽

Yukihiro Shirota ◽

Taro Kawane ◽

Hitoshi Omura ◽

Tatsuo Kumai ◽

...

Keyword(s):

Adverse Events ◽

Anastomotic Stenosis ◽

Technical Success ◽

Long Term Outcomes ◽

Endoscopic Retrograde ◽

Technical Success Rate ◽

Registration Number ◽

Clinical Trial Register

AbstractThere is limited evidence supporting the usefulness of endoscopic retrograde pancreatic drainage (ERPD) for symptomatic pancreaticojejunal anastomotic stenosis (sPJS). We examined the usefulness of ERPD for sPJS. We conducted a retrospective analysis of 10 benign sPJS patients. A forward-viewing endoscope was used in all sessions. Following items were evaluated: technical success, adverse events, and clinical outcome of ERPD. The technical success rate was 100% (10/10) in initial ERPD; 9 patients had a pancreatic stent (no-internal-flap: n = 4, internal-flap: n = 5). The median follow-up was 920 days. Four patients developed recurrence. Among them, 3 had a stent with no-internal-flap in initial ERPD, the stent migrated in 3 at recurrence, and a stent was not placed in 1 patient in initial ERPD. Four follow-up interventions were performed. No recurrence was observed in 6 patients. None of the stents migrated (no-internal-flap: n = 1, internal-flap: n = 5) and no stents were replaced due to stent failure. Stenting with no-internal-flap was associated with recurrence (p = 0.042). Mild adverse events developed in 14.3% (2/14). In conclusions, ERPD was performed safely with high technical success. Recurrence was common after stenting with no-internal-flap. Long-term stenting did not result in stent failure.Clinical trial register and their clinical registration number: Nos. 58-115 and R2-9.

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