{"id":92236,"date":"2016-07-09T02:34:24","date_gmt":"2016-07-09T02:34:24","guid":{"rendered":"http:\/\/healthmedicinet.com\/i\/structural-effects-of-sprifermin-in-knee-osteoarthritis-a-post-hoc-analysis-on-cartilage-and-non-cartilaginous-tissue-alterations-in-a-randomized-controlled-trial\/"},"modified":"2016-07-09T02:34:24","modified_gmt":"2016-07-09T02:34:24","slug":"structural-effects-of-sprifermin-in-knee-osteoarthritis-a-post-hoc-analysis-on-cartilage-and-non-cartilaginous-tissue-alterations-in-a-randomized-controlled-trial","status":"publish","type":"post","link":"https:\/\/healthmedicinet.com\/i\/structural-effects-of-sprifermin-in-knee-osteoarthritis-a-post-hoc-analysis-on-cartilage-and-non-cartilaginous-tissue-alterations-in-a-randomized-controlled-trial\/","title":{"rendered":"Structural effects of sprifermin in knee osteoarthritis: a post-hoc analysis on cartilage and non-cartilaginous tissue alterations in a randomized controlled trial"},"content":{"rendered":"

Study design<\/h4>\n

Details of study design and patient inclusion have been reported 8<\/a>]. In brief, in this multicenter, randomized, double blind, placebo-controlled trial,
\n (ClinicalTrials.gov identifier: NCT01033994), sprifermin was evaluated as a single
\n treatment and as a multiple-dose regimen with three doses of either 10\u00a0?g, 30\u00a0?g,
\n or 100\u00a0?g with 21, 42 and 63 patients respectively, and matched placebo groups of
\n 7, 14 and 21 patients, respectively. Patients were aged ?40\u00a0years, had an established
\n diagnosis of primary tibio-femoral knee OA according to American College of Rheumatology
\n clinical and radiologic criteria, with Kellgren-Lawrence (KL) grade 2 or 3 disease
\n in the target knee 10<\/a>]. Altogether 477 patients were screened and 192 were randomized (24 to the single-dose
\n cohorts and 168 to the multiple-dose cohorts. All patients in the single-dose cohorts
\n received treatment with the study drug and completed the trial. All patients in the
\n multiple-dose cohorts received ?1 dose of study medication, with 168 forming the modified
\n intent-to-treat population; 156 (92.9\u00a0%) completed the trial.\n <\/p>\n

Similar to the recently reported post-hoc analysis on quantitative cartilage parameters
\n 11<\/a>], the current sqMRI analysis focuses on subjects with baseline and 12\u00a0month data in
\n the cohort that received sprifermin 100\u00a0?g (n<\/em>?=?57) (since this was the dosing regimen on which significant drug efficacy was observed
\n 8<\/a>]), and in those who were randomized, in parallel, to receive matching placebo (n<\/em>?=?18). Since this multicenter trial enrolled cohorts sequentially using a dose-ascending
\n approach across 30 sites on multiple continents 11<\/a>], a comparison of the 100\u00a0?g subgroup with a combined placebo subgroup incorporating
\n all dosages (n<\/em>?=?42) was not warranted. The detailed flow-chart of inclusion of the current analysis
\n is presented in Fig.\u00a01<\/a>.<\/p>\n

\"thumbnail\"Fig. 1.<\/strong><\/a> Detailed flow-chart of subject inclusion to the 100\u00a0?g subgroup\n <\/p>\n

Primary end points and assessments<\/h4>\n

The primary efficacy end point was the longitudinal change from baseline in central
\n medial tibio-femoral compartment cartilage thickness at 6\u00a0months and 12\u00a0months, as
\n assessed using qMRI 8<\/a>].\n <\/p>\n

Secondary end points and assessments<\/h4>\n

Secondary imaging end points included total and compartmental femorotibial cartilage
\n thickness and volume as assessed by qMRI, measurement of joint space width by fixed-flexion
\n weight-bearing radiography, and assessment of bone marrow lesions (BMLs), cartilage,
\n menisci, osteophytes, effusion, and synovitis by sqMRI using the modified Whole-Organ
\n Magnetic Resonance Imaging Score (WORMS) at baseline, 3, 6, and 12\u00a0months follow-up
\n 12<\/a>].\n <\/p>\n

MRI acquisition<\/h4>\n

MRIs were acquired using 1.5\u00a0T or 3\u00a0T systems. Axial, coronal, and sagittal intermediate-weighted
\n turbo or fast spin\u2013echo fat-suppressed sequences were used for semiquantitative whole
\n joint assessment of structural tissue pathology, with identical parameters, software
\n and hardware used at baseline and follow-up. Image parameters were as follows: slice
\n thickness 3.0\u00a0mm, in-plane resolution 0.55 \u00d7 0.55\u00a0mm, repetition time 3,600\u20134,000\u00a0msec,
\n and echo time 30\u201340\u00a0msec. In addition the double-oblique coronal spoiled gradient-recalled
\n sequences with fat suppression or water excitation that were acquired for cartilage
\n thickness determination using quantitative MRI were considered for sqMRI assessment
\n with the following acquisition paramaters: contiguous slice thickness 1.5\u00a0mm, in-plane
\n resolutions 0.23 \u00d7 0.23\u00a0mm to 0.32 \u00d7 0.32\u00a0mm, repetition time 18\u201350\u00a0msec, echo time
\n 6.5\u201314\u00a0msec, flip angle 15\u201320\u00b0.\n <\/p>\n

MRI interpretation<\/h4>\n

Four musculoskeletal radiologists (FWR, AG, MDC, MDM), with 7\u201316 years experience
\n in standardized sqMRI assessment of knee OA, graded cartilage status, BMLs, osteophytes,
\n effusion, synovitis and meniscal morphology according to the WORMS system 12<\/a>] with blinding to treatment, radiographic OA grade and clinical data. In addition
\n to the published WORMS scale medial and lateral meniscal extrusion was assessed on
\n the coronal plane according to previous publications 13<\/a>], 14<\/a>] and graded as follows: 0?=?no meniscal extrusion,1?=?extrusion??50\u00a0%, 2?=?extrusion???50\u00a0%.
\n Baseline and follow-up MRIs were presented sequentially, with the chronological acquisition
\n order known to the readers. The four readers assessed the images independently with
\n an equal number of examinations assigned to each reader.\n <\/p>\n

Statistical analysis<\/h4>\n

Statistical analyses were performed using SAS software (version 9.1; SAS Institute).
\n Included in the current analysis were patients from the 100\u00a0?g and matched placebo
\n subgroups with complete MRI datasets with all features and subregions scorable. Analyses
\n included multi-dimensional assessment: (a) A delta-subregional approach was applied,
\n which adds the number of subregions<\/em> (total of 14 articular subregions for cartilage and BMLs on a knee level, 5 subregions
\n each for the medial and lateral tibio-femoral [MTFJ, LTFJ] and 4 subregions for the
\n patello-femoral [PFJ] compartment) showing worsening (0), no change (0) or improvement
\n (0). As an example, 5 subregions showing worsening, 7 subregions showing improvement
\n and 3 subregions showing no change will result in a delta-subregion change of ?2.
\n (b) In addition, a delta-sum approach was used, which adds the absolute scores of all subregions<\/em> combined per compartment or for the whole knee. Analyses were performed on a whole
\n knee level and separately for MTFJ, LTFJ and PFJ compartments for all subgroups. Mann\u2013Whitney???Wilcoxon
\n tests assessed differences between treatment groups. In sensitivity analysis adjusting
\n for baseline values, analysis of covariance (ANCOVA) on ranked baseline and post baseline
\n values was performed. P<\/em>-values were not adjusted for multiple testing.\n <\/p>\n","protected":false},"excerpt":{"rendered":"

Study design Details of study design and patient inclusion have been reported 8]. In brief, in this multicenter, randomized, double blind, placebo-controlled trial, (ClinicalTrials.gov identifier: NCT01033994), sprifermin was evaluated as a single treatment and as a multiple-dose regimen with three doses of either 10\u00a0?g, 30\u00a0?g, or 100\u00a0?g with 21, 42 and 63 patients respectively, and Read More<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[],"tags":[],"class_list":["post-92236","post","type-post","status-publish","format-standard","hentry"],"_links":{"self":[{"href":"https:\/\/healthmedicinet.com\/i\/wp-json\/wp\/v2\/posts\/92236","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/healthmedicinet.com\/i\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/healthmedicinet.com\/i\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/healthmedicinet.com\/i\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/healthmedicinet.com\/i\/wp-json\/wp\/v2\/comments?post=92236"}],"version-history":[{"count":0,"href":"https:\/\/healthmedicinet.com\/i\/wp-json\/wp\/v2\/posts\/92236\/revisions"}],"wp:attachment":[{"href":"https:\/\/healthmedicinet.com\/i\/wp-json\/wp\/v2\/media?parent=92236"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/healthmedicinet.com\/i\/wp-json\/wp\/v2\/categories?post=92236"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/healthmedicinet.com\/i\/wp-json\/wp\/v2\/tags?post=92236"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}