NATIONAL INSTITUTE FOR HEALTH AND CARE EXCELLENCE

Transcription

1 NATIONAL INSTITUTE FOR HEALTH AND CARE EXCELLENCE INTERVENTIONAL PROCEDURES PROGRAMME Interventinal prcedure verview f jint distractin fr ankle stearthritis Ostearthritis f the ankle is caused by deteriratin f the cartilage and underlying bne in the ankle jint, resulting in stiffness, swelling, pain and difficulty in walking. In jint distractin fr ankle stearthritis, an peratin is dne t separate the bnes n either side f the ankle jint and an external frame is fixed t these bnes t hld them apart and allw the damaged cartilage t heal. Intrductin The Natinal Institute fr Health and Care Excellence (NICE) has prepared this interventinal prcedure (IP) verview t help members f the Interventinal Prcedures Advisry Cmmittee (IPAC) make recmmendatins abut the safety and efficacy f an interventinal prcedure. It is based n a rapid review f the medical literature and specialist pinin. It shuld nt be regarded as a definitive assessment f the prcedure. Date prepared This IP verview was prepared in February 2015 and updated in August Prcedure name Jint distractin fr ankle stearthritis Specialist scieties British Orthpaedic Ft & Ankle Sciety British Limb Recnstructin Sciety. IP verview: jint distractin fr ankle stearthritis Page 1 f 41

2 Descriptin Indicatins and current treatment Ostearthritis f the ankle is the result f prgressive deteriratin f the articular cartilage f the jint. Articular cartilage deterirates because f injury, r wear and tear. This leads t expsure f the bne surface. Symptms include pain, stiffness, swelling and difficulty walking. Treatment fr ankle stearthritis depends n the severity f the disease. Cnservative treatments include analgesics and crticsterid injectins t relieve pain and inflammatin, and physitherapy and prescribed exercise t imprve functin and mbility. When symptms are severe, surgery may be indicated. Optins include arthrscpic surgery (t remve lse bdies and bne spurs and t smth the cartilage surfaces f the ankle jint), fusin surgery r ttal ankle replacement. What the prcedure invlves Jint distractin fr ankle stearthritis aims t fflad and mdify the mechanical envirnment in stearthritic jints t allw cartilage regrwth. Intra-articular surgery (such as debridement) may be dne befre distractin with the aim f stimulating cartilage healing. With the patient under spinal blck r general anaesthesia, an external frame is fitted t the ankle. The frame is secured t the tibia and the ft with pins and wires. The ankle is distracted ver several days, gradually increasing the distance between the cartilaginus surfaces f the jint (usually up t abut 5 mm). Distractin is usually maintained fr abut 2 3 mnths befre the frame is remved. During this time, the patient is able t walk. The distractin is thught t enhance cntinuus flw f synvial fluid thrugh the jint and this is claimed t supprt chndrcyte nutritin and regeneratin f cartilage. Hwever, the exact mechanisms that may lead t cartilage regeneratin during distractin are nt knwn. Literature review Rapid review f literature The medical literature was searched t identify studies and reviews relevant t jint distractin fr ankle stearthritis. The fllwing databases were searched, cvering the perid frm their start t 27 August 2015: MEDLINE, PREMEDLINE, EMBASE, Cchrane Library and ther databases. Trial registries and the Internet were als searched. N language restrictin was applied t the searches (see appendix C fr details f search strategy). Relevant published studies identified IP verview: jint distractin fr ankle stearthritis Page 2 f 41

3 during cnsultatin r reslutin that are published after this date may als be cnsidered fr inclusin. The fllwing selectin criteria (table 1) were applied t the abstracts identified by the literature search. Where selectin criteria culd nt be determined frm the abstracts the full paper was retrieved. Table 1 Inclusin criteria fr identificatin f relevant studies Characteristic Publicatin type Patient Interventin/test Outcme Language Criteria Clinical studies were included. Emphasis was placed n identifying gd quality studies. Abstracts were excluded where n clinical utcmes were reprted, r where the paper was a review, editrial, r a labratry r animal study. Cnference abstracts were als excluded because f the difficulty f appraising study methdlgy, unless they reprted specific adverse events that were nt available in the published literature. Patients with ankle stearthritis. Jint distractin. Articles were retrieved if the abstract cntained infrmatin relevant t the safety and/r efficacy. Nn-English-language articles were excluded unless they were thught t add substantively t the English-language evidence base. List f studies included in the IP verview This IP verview is based n abut 180 patients frm 2 randmised cntrlled trials (RCTs) 1-4 and 6 case series 3-8. Other studies that were cnsidered t be relevant t the prcedure but were nt included in the main extractin table (table 2) have been listed in appendix A. IP verview: jint distractin fr ankle stearthritis Page 3 f 41

4 Table 2 Summary f key efficacy and safety findings n jint distractin fr ankle stearthritis Study 1 Saltzman CL (2012) Details Study type Cuntry RCT USA Recruitment perid Study ppulatin and number Age and sex Patient selectin criteria Technique n=36 (18 fixed distractin versus 18 distractin with mtin) patients with advanced ankle stearthritis. Mean 41.5 years; 67% (24/36) male BMI: mean 29.9 kg/m 2 Patients with symptmatic, islated, unilateral end-stage ankle stearthritis IP 1276 [IPG538] All prcedures were dne by 1 r 2 surgens using the same technique. Patients were treated by an arthrscpic ankle jint lavage with remval f any extra-articular anterir sseus stephytes befre the distractin. If the anterir stephytes were t large t remve arthrscpically, they were remved by an pen incisin thrugh an extensin f the arthrscpic prtals. Intra-articular jint debridement was nt perfrmed. Fr patients in the fixed distractin grup, distractin rds withut hinges were use. Fr patients in the distractin with mtin grup, distractin rds with hinges were used, with an unhinged psterir rd being detached during mtin therapy. During the prcedure, the ankle was distracted 5 mm as measured with use f flurscpy. Patients in the mtin grup began therapy 1 week after the prcedure. The fixatr was remved between 85 and 95 days after applicatin. The patient then wre a remvable belw-the-knee Velcr-strapped rcker-bttm bt fr ne mnth after fixatr remval and began weight-bearing in the bt. The patient gradually returned t full weight-bearing withut bt immbilisatin by 6 mnths. Fllw-up Cnflict f interest/surce f funding 24 mnths after frame remval This prject was funded by a research grant frm the Natinal Institutes f Health. One r mre f the authrs received payments r services, either directly r indirectly, frm a third party in supprt f an aspect f this wrk. In additin, ne r mre f the authrs, r his r her institutin, has had a financial relatinship, in the 36 mnths prir t submissin f this wrk, with an entity in the bimedical arena that culd be perceived t influence r have the ptential t influence what is written in this wrk. Analysis Fllw-up issues: 4 patients wh enrlled in the study withdrew befre having surgery. Fllw-up evaluatins were dne at 1, 3, 6, 9 weeks after the prcedure and at 1, 26, 52 and 104 weeks after fixatr remval. In the mtin grup, n patients were lst t fllw-up and 1 patient had cnversin t an arthrdesis between the 52- and 104-week visits after fixatr remval. In the fixed grup, 1 patient drpped ut befre the 1-week visit pst fixatr remval, 1 drpped ut after the 1-week visit pst fixatr remval, and 1 drpped ut after the 52-week visit. Three additinal patients underwent ankle arthrdesis, 1 befre the 52-week visit and 2 between the 52-week and 104-week visits. Few values were missing at the 1-week visit after fixatr remval due t administrative prblems unrelated t the patient s cnditin. Study design issues: Patients cmpleted the self-assessment ankle stearthritis scale (AOS, higher scre indicates mre pain and disability) and SF-36 questinnaires at each visit. Patients were randmised t 1 f the 2 treatment grups with use f a randmisatin schedule prepared in advance. Randmisatin tk place in the perating rm after arthrscpic r pen resectin f the anterir stephytes had been perfrmed. Subjects were randmised in blck sizes f 2 and 4, determined at randm. Sealed envelpes cntaining the treatment assignments fr sequential patients were pened and assignments were made in the perating rm after stephyte remval had been cmpleted and the incisins had been clsed. Study ppulatin issues: Nne reprted. Other issues: Nne. IP verview: jint distractin fr ankle stearthritis Page 4 f 41

5 Key efficacy and safety findings Efficacy Number f patients analysed: 36 (18 fixed distractin versus 18 distractin with mtin) Cnversin t arthrdesis Fixed grup: 17% (3/18) f patients were treated by ankle arthrdesis, 1 befre the 52-week visit and 2 between the 52-week and 104-week visits. Mtin grup: 6% (1/18) f patients had cnversin t an arthrdesis between the 52-week and 104-week visits. Cmbined AOS scre (pints) lngitudinal analysis (assuming data missing at randm). Time pint Fixed grup Mtin grup Difference (fixed grup mtin grup) p value Pre-treatment week after fixatr remval 26 weeks after fixatr remval 52 weeks after fixatr remval 104 weeks after fixatr remval < < <0.01 (between grup difference in means) Befre-after difference in mean AOS scres (scre at 104 weeks versus baseline) Safety Pin-track infectins: 43 episdes in 53% (19/36) f patients All infectins were treated initially with ral antibitics (cephalexin, 250 mg 4 times daily fr 7 days). Fur persisted, and the pins were remved. Tw f these 4 infectins ccurred in patients wh were thught t have acute stemyelitis and were treated t reslutin with 6 weeks f intravenus antibitics. Areas f numbness in the medial calcaneal branch f the tibial nerve and the deep perneal distributin nt the great te after distractr placement: 22% (8/36) f patients. When numbness was identified, X-rays were made and, if distractin exceeded 5 mm, it was reduced t this level. N ther treatment was given. Fur cases reslved with the frame n, 2 reslved within 3 mnths after frame remval, and 2 patients were left with residual numbness. Tw years after frame remval, 1 patient had mild decreased sensatin n the drsal aspect f the hallux, and the ther had mild tingling n the plantar aspect f the ft that cntinued t decrease. With the small numbers studied, a significant assciatin between neurpraxia and treatment grup culd nt be identified. A symptmatic deep venus thrmbsis distal t the knee was reprted in 3% (1/36) f patients and was treated by anticagulatin therapy. Mtin grup: (-57%), p<0.01 Fixed grup: (-23%), p<0.02 Physical cmpnent summary (PCS) f the SF-36 questinnaire The mtin grup shwed better PCS utcmes than the fixed grup at 26 weeks after fixatr remval (p=0.02) and at 104 weeks after fixatr remval (p=0.05) but nt at 52 weeks after fixatr remval (p=0.49). Abbreviatins used: AOS, ankle stearthritis scale; BMI, bdy mass index; PCS, physical cmpnent summary; SD, standard deviatin; SF, shrt frm. IP verview: jint distractin fr ankle stearthritis Page 5 f 41

6 Study 2 Nguyen M P (2015) Details Study type Cuntry Chrt fllw-up f Saltzman (2012) study ppulatin. USA Recruitment perid Study ppulatin and number Age and sex Patient selectin criteria Technique n=36 (18 fixed distractin and 18 distractin with mtin) patients with advanced ankle stearthritis. Mean 41.5 years; 67% (24/36) male BMI: mean 29.9 kg/m 2 Patients with symptmatic, islated, unilateral ankle stearthritis with a Kellgren-Lawrence grade f 3 r 4, skeletal maturity and age n greater than 60, failure f mre than a year f nnsurgical treatment, including 3 mnths f cntinuus treatment with nnsteridal anti-inflammatry drugs and 3 mnths f unlading treatment, and an ability t maintain the extremity nn-weight-bearing by using ambulatry aids. Exclusin criteria: inflammatry r crystal arthritis, diabetes, severe systemic illness, fibrmyalgia, peripheral neurpathy, reflex sympathetic dystrphy, a previus infectin f the ankle, a neurarthrpathic ankle, ther symptmatic jints f the ipsilateral lwer extremity, cntralateral ankle stearthritis, ankle r hindft malalignment, living mre than 483 km away frm the hspital and current alchl r drug abuse. All prcedures were dne by 1 r 2 surgens using the same technique. Patients were treated by an arthrscpic ankle jint lavage with remval f any extra-articular anterir sseus stephytes befre the distractin. If the anterir stephytes were t large t remve arthrscpically, they were remved by an pen incisin thrugh an extensin f the arthrscpic prtals. Intra-articular jint debridement was nt perfrmed. Fr patients in the fixed distractin grup, distractin rds withut hinges were use. Fr patients in the distractin with mtin grup, distractin rds with hinges were used, with an unhinged psterir rd being detached during mtin therapy. During the prcedure, the ankle was distracted 5 mm as measured with use f flurscpy. Patients in the mtin grup began therapy 1 week after the prcedure. The fixatr was remved between 85 and 95 days after applicatin. The patient then wre a remvable belw-the-knee Velcr-strapped rcker-bttm bt fr ne mnth after fixatr remval and began weight-bearing in the bt. The patient gradually returned t full weight-bearing withut bt immbilisatin by 6 mnths. Fllw-up Cnflict f interest/surce f funding Mean 8.3 years This prject was funded by a research grant frm AO Nrth America. The riginal study was funded by a grant frm the Natinal Institutes f Health, US department f Health & Human Services. Analysis Fllw-up issues: 4 patients wh enrlled in the study withdrew befre having surgery. The primary utcme, ankle status (defined as preserved ankle jint r cnversin t ttal ankle replacement r ankle arthrdesis) was available in 81% (29/36) patients at mean 8.3 years f fllw-up; 1 patient refused t participate and 6 were lst t fllw-up. 22 patients cmpleted the self-assessment ankle stearthritis scale (AOS, higher scre indicates mre pain and disability) and the physical cmpnent summary (PCF) f the SF-36 questinnaire at fllw-up. Cmplete AOS and SF-36 scres were available fr 61% (22/36) f patients, including 5 wh cmpleted the surveys remtely withut a return visit. Study design issues: N statistical cmparisns f AOS and PCF scres befre distractin and at 5-10 years f fllw-up were perfrmed because f the limited number f patients with cmplete functinal scres at 5-10 years. Study ppulatin issues: Nne reprted. Other issues: Nne. IP verview: jint distractin fr ankle stearthritis Page 6 f 41

7 Key efficacy and safety findings Efficacy Number f patients analysed: 29 Cnversin (n=29) Ankle arthrdesis: 28% (8/29) Mean age at cnversin: 42±7.5 years Ttal ankle arthrplasty: 17% (5/29) Mean age at cnversin: 58±6.5 years Patients with native ankle jint: 55% (16/29) Of the 13 cnversins, 2 were perfrmed within 1 year after ankle distractin, 3 in the secnd year, 1 in the third year, 1 in the fifth year, 3 in the sixth year, 2 in the seventh year and 1 in the eighth year. Safety N safety utcmes nt already reprted in study 1. Predictrs f ankle survival at mean 8.3 years HR (95% CI) p value Fixed distractin versus mtin AOS scre at 2 years (42 r less versus mre than 42) Imprvement f AOS scre at 2 years ( ) < ( ) ( ) 0.73 Age at distractin* 0.91 ( ) 0.04 *Older patients had a lwer failure rate cmpared against thse wh were 1 year yunger. Mean AOS scres (at 5-10 years, n=22) Native ankle grup: 59.8±20.7 (versus 60.7±12.2 befre distractin) Cnversin grup: 42.5±35.3 (versus 59.5±12.5 befre distractin) Physical cmpnent summary (PCS) f the SF-36 questinnaire (at 5-10 years, n=22) Native ankle grup: 32.8±9.5 Cnversin grup: 37.8±11.8 Imaging findings (n=10 with native ankle) Ankle images cnsistently demnstrated subchndral sclersis, stephyte frmatin and sseus defrmity cnsistent with Kellgren- Lawrence grade-3 r 4 ankle stearthritis. Final fllw-up CT scans revealed sme lss f the benefit seen at 2 years, with increases in cystic frmatin and sseus sclersis cnsistent with the natural prgressin f stearthritis. Abbreviatins used: AOS, ankle stearthritis scale; BMI, bdy mass index; CI, cnfidence interval; HR, hazard rati; PCS, physical cmpnent summary; SD, standard deviatin; SF, shrt frm. IP verview: jint distractin fr ankle stearthritis Page 7 f 41

8 Study 3 Marijnissen ACA (2002) Details Study type Case series (prspective study) and RCT (patients were included in Marijnissen 2013) Cuntry Recruitment perid Study ppulatin and number Netherlands (cases series and RCT) and Belgium (cases series) (case series) and (RCT) n=74 patients with severe ankle stearthritis (OA) Case series: n=57 RCT: n=17 (9 jint distractin vs 8 debridement) Age and sex Case series: mean 44 years; 54% male RCT: mean 44.5 years; 65% male Patient selectin criteria Case series, inclusin criteria: refractry, severe OA; exclusin criteria: intra-articular infectin, OA in bth ankle jints and psychlgical prblems that wuld nt allw a 3-mnth perid f distractin. RCT, inclusin criteria: scres n 3 f the 5 clinical parameters (pain, functinal impairment, physical impairment, impaired jint mbility and jint space narrwing) exceeding 50% f the maximum scre. Exclusin criteria: same as in the case series. Technique Case series: distractin was preceded, when necessary, by arthrscpic debridement. Intra-articular fibrtic tissue and stephytes, if present, were remved by shaving in 35 f 57 patients s that the ft culd be placed in the plantigrade psitin that is necessary fr distractin. Fllw-up Cases series: mean 2.8 years Cnflict f interest/surce f funding RCT: debridement was perfrmed in 7 f the 9 patients in the jint distractin grup and in all 8 patients in the debridement cntrl grup. N articular cartilage surgery was perfrmed. Fr bth: distractin f the jint was dne twice a day fr 0.5 mm each until a ttal distractin f at least 5 mm was reached. In 2 patients in the cases series, equinus psitin f the ft was gradually crrected in cmbinatin with the distractin. Ankle distractin was maintained fr 3 mnths. Full weight bearing was allwed within a week after surgery. The lss f plantar flexin in the ankle during walking was cmpensated by use f a sle fitted belw the ft. Physical therapy and medicatin were administered at the patient s request nly. After remval f the frame, all patients were able t walk with r withut crutches. RCT: 1 year The study was supprted by a grant frm the Dutch Arthritis Assciatin. Analysis Fllw-up issues: Case series: 11 patients had been fllwed up fr less than 1 year and were therefre nt included in the analysis. Study design issues: Pain, functin, clinical status, ankle jint mbility, radigraphic jint space width, and subchndral sclersis were evaluated befre treatment and yearly thereafter. One bserver wh was nt invlved in the surgery perfrmed the clinical examinatins f all patients in the 3 hspitals. X-rays were evaluated by 1 blinded bserver. The Wilcxn signed rank test fr crrelated data was used t cmpare data btained befre and after treatment and t cmpare data frm different time pints after treatment. Fr the RCT, pwer analysis dictated 8 patients per grup. The Mann-Whitney U test was used t evaluate if jint distractin had a better clinical result than arthrscpic debridement alne. Statistical evaluatin was perfrmed by intent-t-treat analysis fr all randmised patients. The Spearman crrelatin was used t cmpare clinical utcme with radigraphic parameters. Study ppulatin issues: The values befre treatment in the debridement grup were nt significantly different frm thse in the distractin grups in the RCT and in the case series. Other issues: Patient verlap with Marijnissen (2014) and with Plegmakers (2005) studies which are bth included in table 2. IP verview: jint distractin fr ankle stearthritis Page 8 f 41

9 Key efficacy and safety findings Efficacy Number f patients analysed: n=74 patients with severe ankle stearthritis (OA) Case series: n=57 RCT: n=17 (9 jint distractin vs 8 debridement) Pain Case series One year after the prcedure (n=38), the average scre fr pain decreased by 38% (p<0.0001). 23% (13/57) f patients withdrew frm the study because f persistent pain. 62% (8/13) f patients withdrew within 1 year after distractin. All the patients wh withdrew were treated by arthrdesis. Percentage f treated patients shwing clinically imprtant differences in pain during fllw-up Fllw-up % f patients shwing 35% imprvement in pain 1 year (n=38) 55 2 years (n=27) 63 3 years (n=19) 58 4 years (n=10) 50 5 years (n=7) 71 6 years (n=6) 83 7 years (n=1) 100 The percentages f patients wh shwed 35% imprvement in clinical parameters were calculated accrding t the Outcme Measures in Rheumatlgy Clinical Trials criteria. Safety Case series: 28% (16/57) f patients had infectins at the pin sites which were effectively treated by antibitics. In 14% (8/57) f patients, the pins thrugh the freft brke, prbably because f excessive strain during walking. In 62.5 % (5/8) f these patients, the brken pin was remved, and in 37.5 % (3/8) f patients, the pin was replaced; lcal infectins were prevented r treated by antibitics. RCT: 33% (3/9) f patients had infectins at the pin sites. In 1 patient, the pin thrugh the freft was replaced, and in 1 patient, the pin thrugh the prximal tibia was replaced. RCT One year after the prcedure (n=9), the average scre fr pain decreased frm 72% t 37% f the maximum scre (p<0.003). In the grup treated with debridement alne, 37.5 % (3/8) f patients did nt reach the 1 year fllw-up despite the experimental setup because f persistent severe pain. They were cnsidered treatment failures and underwent jint distractin between 4 mnths and 11 mnths after debridement. Fr these 3 patients, the last evaluatin befre jint distractin was used t calculate the averages fr the cntrl grup. The effects f jint distractin in these 3 patients were nt included in the jint distractin grup. The 3 patients wh were treated by distractin after debridement had failed had a 59% imprvement in pain. Functin Case series One year after the prcedure (n=38), the average scre fr functin increased by 69% (p<0.0001). At 3 years (n=19), the average scre fr functin increased significantly cmpared against the average scre at 1 year: +20% (p<0.03). IP verview: jint distractin fr ankle stearthritis Page 9 f 41

10 Percentage f treated patients shwing clinically imprtant differences in functin during fllw-up Fllw-up % f patients shwing 35% imprvement in functin 1 year (n=38) 53 2 years (n=27) 41 3 years (n=19) 53 4 years (n=10) 70 5 years (n=7) 86 6 years (n=6) years (n=1) 100 The percentages f patients wh shwed 35% imprvement in clinical parameters were calculated accrding t the Outcme Measures in Rheumatlgy Clinical Trials criteria. RCT One year after the prcedure (n=9), the average scre fr functin increased frm 19% t 61% f the maximum scre (p<0.004). The 3 patients wh were treated by distractin after debridement had failed had a 55% imprvement in functin. Clinical cnditin Case series One year after the prcedure (n=38), the average scre fr clinical cnditin increased by 120% (p<0.0001). At 3 years (n=19), the average scre fr clinical cnditin increased significantly cmpared against the average scre at 1 year: +43% (p<0.05). Percentage f treated patients shwing clinically imprtant differences in clinical cnditin during fllw-up Fllw-up % f patients shwing 35% imprvement in clinical cnditin 1 year (n=38) 55 2 years (n=27) 63 3 years (n=19) 68 4 years (n=10) 60 5 years (n=7) 71 6 years (n=6) 83 7 years (n=1) 100 The percentages f patients wh shwed 35% imprvement in clinical parameters were calculated accrding t the Outcme Measures in Rheumatlgy Clinical Trials criteria. RCT One year after the prcedure (n=9), the average scre fr clinical status increased frm 20% t 69% f the maximum scre (p<0.005). The 3 patients wh were treated by distractin after debridement had failed had a 55% imprvement in clinical cnditin. IP verview: jint distractin fr ankle stearthritis Page 10 f 41

11 Jint mbility Case series One year after the prcedure (n=38), the average scre fr jint mbility increased by 8% (p nt significant). Percentage f treated patients shwing clinically imprtant differences in jint mbility during fllw-up Fllw-up % f patients shwing 35% imprvement in jint mbility 1 year (n=38) 13 2 years (n=27) 30 3 years (n=19) 32 4 years (n=10) 10 5 years (n=7) 14 6 years (n=6) 17 7 years (n=1) 0 The percentages f patients wh shwed 35% imprvement in clinical parameters were calculated accrding t the Outcme Measures in Rheumatlgy Clinical Trials criteria. RCT One year after the prcedure (n=9), the average scre fr mbility decreased frm 56% t 46% f the maximum scre (p value nt significant). Impairment f maximum walking distance (case series patients) Fllw-up Scre fr impaired walking distance (mean±sd) Befre the prcedure 1.46± year (n=38) 0.92±0.20 < years (n=7) 0.00±0.00 <0.04 p value (versus baseline) Jint space width Case series This was nly evaluated in patients fr whm the X-ray was useful fr evaluatin (n=17) and wh had mre than 10% jint space narrwing befre treatment: 12 patients at 1 year, 10 at 2 years, 7 at 3 years, 3 at 4 years, and 3 at 5 years. One year after the prcedure (n=12), the average jint space width increased by 17% (p<0.04). At 3 years (n=7), the mean jint space width increased significantly cmpared against the mean width at 1 year: +10% (p<0.05). In the remaining 5 patients, jint space narrwing in the affected jint befre treatment was <10%. On average, these patients shwed n significant change in jint space width ver time. Percentage f treated patients shwing clinically imprtant differences in jint space width during fllw-up Fllw-up % f patients shwing 25% imprvement in jint space width 1 year (n=12) 33 2 years (n=10) 70 3 years (n=7) 71 IP verview: jint distractin fr ankle stearthritis Page 11 f 41

12 4 years (n=3) 67 5 years (n=3) 67 The percentages f patients wh shwed 25% imprvement in bjective parameters were calculated accrding t the Outcme Measures in Rheumatlgy Clinical Trials criteria. Subchndral sclersis Case series This was nly evaluated in patients in whm the X-ray was useful fr evaluatin (n=17) and wh had increased subchndral bne density (cmpared against the cntralateral ankle) befre treatment: 10 patients at 1 year, 7 at 2 years, 5 at 3 years, 3 at 4 years, and 2 at 5 years. One year after the prcedure (n=10), the subchndral bne density decreased by 10% (p<0.003). At 3 years (n=5), subchndral bne density decreased by an additinal 7% cmpared against it at 1 year (p>0.23). In the remaining 7 patients withut measurable subchndral sclersis befre treatment, n significant decrease in bne density ver time was fund n average. Percentage f treated patients shwing clinically imprtant differences in jint space width during fllw-up Fllw-up % f patients shwing 25% imprvement in jint space width 1 year (n=10) 33 2 years (n=7) 70 3 years (n=5) 71 4 years (n=3) 67 5 years (n=2) 67 The percentages f patients wh shwed 25% imprvement in bjective parameters were calculated accrding t the Outcme Measures in Rheumatlgy Clinical Trials criteria. Abbreviatins used: NS, nt significant; OA, stearthritis, SD, standard deviatin. IP verview: jint distractin fr ankle stearthritis Page 12 f 41

13 Study 4 Marijnissen ACA (2014) Details Study type Cuntry Recruitment perid Study ppulatin and number Age and sex Patient selectin criteria Technique Fllw-up Cnflict f interest/surce f funding Case series cmpiled frm 2 studies: ne pen prspective multicentre study (same patients as in Marijnissen 2002) and ne RCT (same patients as in Saltzman 2012) Netherlands and Belgium (cases series) and USA (RCT) (case series) and (RCT) n=111 patients with severe ankle stearthritis Case series: n=75 RCT: n=36 (18 fixed ankle distractin vs 18 jint mtin permitted ankle distractin) Mean 42.7 years; 60% male (all patients) Case series: mean 43.3 years; 57% male; BMI nt reprted RCT: mean 41.4 years; 67% male; mean BMI, 29.8 kg/m 2 All patients had severe ankle OA, mstly pst-traumatic and were cnsidered fr arthrdesis. Case series: fixed ankle distractin RCT: fixed r jint mtin permitted ankle distractin. Mean fllw-up: Cases series: 8.1 years RCT: 1.9 years Nt reprted Analysis Fllw-up issues: Nne. Study design issues: The aim f this study was t cnduct survival and regressin analyses t identify predictrs f treatment failure and clinical utcmes, thrugh analysing fllw-up data frm 2 previus studies: ne pen prspective multicentre study (same patients as in Marijnissen 2002) and ne RCT (same patients as Saltzman 2012) Case series: all distractin prcedures were dne by a single surgen in each centre. Pain and functinal disability were evaluated at baseline and every year after the distractin using different questinnaires in the cases series and in the RCT. Bth parameters were expressed as percentage f the maximum scre. In the case series, the Van Valburg functinal disability questinnaire and the bx scale fr pain were used. In the RCT, the Ankle Ostearthritis Scale (AOS) was used. Pain and functinal disability as endpints were defined at 2 years since a 2-year fllw-up measurement was available fr almst all patients in bth chrts. Failures were defined as patients wh underwent an arthrdesis, develped Sudeck s atrphy, had an stetmy r a secnd distractin dne. Failure at 2 years and failure ver time during the entire fllw-up perid were used as endpints. Survival curves with failure as end pint were cnstructed using the Kaplan Meier methd. Survival times were censred at the time f lss t fllw-up r maximum fllw-up. Study ppulatin issues: Mean percentages f the maximum scre fr pain at baseline: 73%±13 % (case series) versus 60%±15% (RCT), p< Other issues: Same patients as in Saltzman (2012) and Marijnissen (2002) and sme patient verlap with Plegmakers (2005). All 3 studies are included in table 2. IP verview: jint distractin fr ankle stearthritis Page 13 f 41

14 Key efficacy and safety findings Efficacy Number f patients analysed: 111 Case series: n=75 RCT: n=36 (18 fixed ankle distractin vs 18 jint mtin permitted ankle distractin) Safety 2 f the 105 patients available fr 2-year fllw-up had develped Sudeck s atrphy. Treatment failures Over a fllw-up f 12 years, 44% f prcedures had failed ( failure definitin abve in study design issues). 17% f prcedures failed within 2 years f jint distractin 37% f prcedures failed within 5 years f jint distractin Within 2 years after ankle distractin (n=96 after 2 years): 17% (18/105) f failures 5% (6/111) patients were lst t fllw-up within 2 years (1 patient died 15 mnths after the prcedure, nt related t the treatment and the reasn fr lss t fllw-up fr the ther 5 was unknwn). 83% (15/18) f patients with treatment failure were treated by arthrdesis. 11% (2/18) f patients with treatment failure develped Sudeck s atrphy. 5% (1/18) f patients with treatment failure were treated by stetmy. Within 5 years after ankle distractin (n=48 after 5 years): 37% f failures. N significant difference in the percentage f failures which ccurred in the first 2 years after jint distractin was fund between the case series and the RCT (respectively 18% vs. 15%, p=0.647) and n significant difference was fund in time t failure between the 2 study grups (p=0.637). The percentage f failure was different in wmen versus men; in wmen there was a 30% failure after 2 years and in men 30% failure was still nt reached after 11 years. Lg-rank test cnfirmed the statistically significant difference in failure during fllw-up between men and wmen (p=0.001). Regressin Analyses The fllwing baseline variables were included in regressin analyses (linear and lgistic, depending n utcme variable) t identify predictrs f failure, pain, and functinal disability at 2 years: gender, age, pain, functinal disability, clinical cnditin, mtin permitted distractin, BMI. Results are presented as Odds Ratis (OR). Only results significant at the p<0.05 level are reprted here. T examine predictrs f failure ver time cx regressin analyses were undertaken, and hazard ratis reprted (HR). Again nly results significant at the p<0.05 level are reprted here. Predictin f failure at 2 years: Univariate lgistic regressin analysis with failure at 2 years after jint distractin as dependent variable Female gender: OR 4.94 (95% CI ), p=0.005 Pain at baseline: OR 1.05 (95% CI ), p= Multivariate lgistic regressin analysis with failure at 2 years after jint distractin as dependent variable Female gender: OR 5.42 (95% CI ), p=0.004 Predictin f pain at 2 years: Univariate linear regressin analysis with pain at 2 years after jint distractin as dependent variable Pain at baseline: ß 0.40 (95% CI 0.08 t 0.73), p=0.015 Functinal disability at baseline: ß 0.35 (95% CI t 0.7), p=0.048 IP verview: jint distractin fr ankle stearthritis Page 14 f 41

15 Mtin permitted distractin: ß (95% CI t -6.0), p=0.005 Multivariate linear regressin analysis with pain at 2 years after jint distractin as dependent variable R 2 =0.144 Mtin permitted distractin: ß (95% CI t -3.04), p=0.021 Pain (average percentage f the maximum scre ± SD) Baseline At last fllw-up Fr the patients wh were still in fllw-up (n=105) Fr the patients whse treatment failed (n=6) 67 %±15 % 38 %±24 % (2 years after ankle distractin) 76 %±15 % 71 %±21 % (last bserved scres befre failure) Predictin f functinal disability at 2 years: Univariate linear regressin analysis with functinal disability at 2 years after jint distractin as dependent variable Pain at baseline: ß 0.38 (95% CI 0.06 t 0.7), p=0.020 Functinal disability at baseline: ß 0.38 (95% CI 0.05 t 0.7), p=0.027 Multivariate linear regressin analysis with functinal disability at 2 years after jint distractin as dependent variable R 2 =0.128 Mtin permitted distractin: ß (95% CI t -4.23), p=0.015 Functinal disability (average percentage f the maximum scre) Baseline At last fllw-up Fr the patients wh were still in fllw-up (n=105) Fr the patients whse treatment failed (n=6) 68 %±15 % 36 %±23 % (2 years after ankle distractin) 67 %±13 % 71 %±18 % (last bserved scres befre failure) Predictin f failure ver time: Univariate Cx regressin analysis with failure after jint distractin as dependent variable Gender: HR 2.83 (95% CI ), p=0.002 Multivariate Cx regressin analysis with failure after jint distractin as dependent variable Gender: HR 2.86 (95% CI ), p=0.002 Abbreviatins used: BMI, bdy mass index; CI, cnfidence interval; HR, hazard rati; OR, dds rati; SD, standard deviatin. IP verview: jint distractin fr ankle stearthritis Page 15 f 41

16 Study 5 Plegmakers JJW (2005) Details Study type Cuntry Case series Recruitment perid Study ppulatin and number Age and sex Belgium and The Netherlands n=22 patients with unilateral pst-traumatic ankle OA severe enugh t be cnsidered fr arthrdesis Mean 37 years; 64% (14/22) male Patient selectin criteria Patients with severe unilateral pst-traumatic ankle OA wh underwent jint distractin between April 1987 and July 1995 at the selected hspitals. Technique Fllw-up Cnflict f interest/surce f funding In each centre a single surgen perfrmed the prcedures. The prcedure was dne under general anaesthesia. Distractin was carried ut ver a distance f 5 mm (0.5 mm twice daily fr 5 days), starting the day after applicatin f the apparatus. Full weight bearing was allwed within a few days after surgery. Generally, all patients used crutches t walk with partial weight bearing n the affected ankle shrtly after leaving hspital. During the subsequent weeks, the walking distance, the frequency, and amunt f lading gradually increased. After weeks, n average at 15±3 weeks after initiatin f treatment, the external fixatin apparatus was remved under general anaesthesia. 7 years minimum Nt reprted Analysis Fllw-up issues: 27 patients met the inclusin criteria, 93% (25/27) culd be traced. Three patients did nt cmplete the questinnaires in apprpriate way fr evaluatin. Therefre, 81% (22/27) f patients treated were available fr evaluatin. Study design issues: The pre-treatment status f patients was evaluated retrspectively using 3 different questinnaires (the Van Valburg questinnaire, the Ankle stearthritis scale (AOS) and a patient satisfactin questinnaire), and by survey f the patients charts. Pst-treatment status (at least 7 years after treatment) was evaluated using the same questinnaires and by physical examinatin. Fr the Van Valburg questinnaire and the AOS, results were expressed as a percentage f the maximum scre. Fr the patient satisfactin scre, results were expressed as the number f patients in each f the 5 categries (frm deteriratin t clear imprvement) fr each parameter. The Wilcxn signed rank test fr paired data was used t cmpare status parameters befre and after treatment and t cmpare retrspectively btained and prspectively btained pre-treatment data. Spearman crrelatin was used fr cmparisn f utcme f different questinnaires. Study ppulatin issues: Causes f OA: 86% (19/22) fracture r subluxatin f the ankle jint; 5% (1/22) cngenital defrmatin; 5% (1/22) defrmatin after plimyelitis; 5% (1/22) nt knwn. Other issues: Patient verlap with Marijnissen 2014 and with Marijnissen 2002 (bth included in table 2) fr 16 patients. IP verview: jint distractin fr ankle stearthritis Page 16 f 41

17 Key efficacy and safety findings Efficacy Number f patients analysed: 22 Treatment failure: 27% (6/22) f patients 83% (5/6) f patients were treated by arthrdesis; 3 within the first year after treatment and 2 fur years after treatment. 17% (1/6) f patients suffered frm an incmplete Sudeck s atrphy. Safety Persisting pain: 27% (6/22) f patients Sudeck s atrphy: 5% (1/22) f patients (unclear if related t the prcedure). Pain (% f the maximum scre, n=16) Questinnaire Clinical evaluatin AOS scre fr pain Mean ± SE pain scre befre jint distractin Mean ± SE pain scre at least 7 years after jint distractin p value 78±3% 30±5% < Further details 67±6% 25±6% < Scre decreased in 87.5% (14/16) f patients after treatment. In 12.5% (2/16) f patients, scre increased; One f these patients culd nly answer 1 ut f the 9 questins in the questinnaire relating t the situatin befre treatment, making the result unreliable. Functinal ability / disability (% f the maximum scre, n=16) Questinnaire Clinical evaluatin (ability) Mean pain scre befre jint distractin Mean ± SE pain scre at least 7 years after jint distractin p value Further details 20±4% 73±6% < Functinal ability increased in all patients, except 1 (pretreatment scre f 60% which remained unchanged after treatment) AOS scre fr disability 74±5% 32±7% < Disability measured by the AOS decreased after treatment in 87.5% (14/16) f patients. In 2 patients the disability scre increased, and 1 f these patients als shwed an increase in pain. Ttal AOS scre (pain and disability) Mean ttal scre befre jint distractin: 69±4% Mean ttal scre at least 7 years after jint distractin: 29±6% p< Clinical status (%) Clinical evaluatin (n=16) Mean scre befre jint distractin: 21±7% IP verview: jint distractin fr ankle stearthritis Page 17 f 41

18 Mean scre at least 7 years after jint distractin: 77±6% p value< In 1 patient, pre-treatment scre was 100% and remained unchanged after jint distractin. In 1 patient, there was a 33% decrease in their clinical status. In 1 patient, physical examinatin was nt recrded adequately in the chart. Ankle mbility (measured in degrees and expressed as a % f the range f mtin f the cntralateral cntrl ankle) Clinical evaluatin (n=16) Mean scre befre jint distractin: 52±7% Mean change: 34±23% p value> 0.39 Mbility increased in 37.5 % (6/16) f patients, decreased in 37.5% (6/16) f patients and remained unchanged in 1 patient. In 3 patients n pre-perative data were available frm the patients charts. Patient satisfactin Wrsened Similar Minimally imprved Imprved Nticeably imprved Functin 7% (1/15) 13% (2/15) 20% (3/15) 7% (1/15) 53% (8/15) Pain 6% (1/16) 13% (2/16) 6% (1/16) 19% (3/16) 56% (9/16) Numbers refer t number f patients wh replied with the respective answer t each item f the Van Valburg questinnaire when cmparing the situatin after jint distractin with that befre treatment at time f evaluatin. One patient was nt able t answer each specific questin with respect t functin. Abbreviatins used: AOS, ankle stearthritis scale; OA, stearthritis; SE, standard errr. IP verview: jint distractin fr ankle stearthritis Page 18 f 41

19 Study 6 Paley D (2008) Details Study type Cuntry Case series USA Recruitment perid Study ppulatin and number Age and sex Patient selectin criteria Technique Fllw-up Cnflict f interest/surce f funding n=23 patients with painful ankle OA Mean 45 years (respnders t the questinnaires nly); 39% (9/23) male Patients treated by hinged ankle distractin with external fixatin wh had a minimum 2-year fllw-up. During the prcedure, the ankle was distracted by 2 mm. The ankle was then distracted at a rate f 1 mm per day frm the day after the prcedure t 5 days after the prcedure. The gal was t distract the ankle up t 8-10 mm. The external fixatin device was maintained fr 3 mnths. Weight bearing was allwed. The patient remved the psterir distractin rd t d daily ankle range-f-mtin exercises and attended physical therapy 3 times a week. Mean 64 mnths (fr the 18 respnders) The main authr is a cnsultant fr Smith & Nephew and Orthfix. Analysis Fllw-up issues: The charts f 32 patients were retrspectively reviewed fr the study and in 72% (23/32) f patients the charts were available fr cmplete review, 9 male, 14 female. 18 patients respnded t the questinnaires; 3 were fund but refused t participate in the study and 11 patients culd nt be lcated. Study design issues: Retrspective study. The prcedures were dne by 4 different surgens. Study ppulatin issues: Diagnses: 87% (20/23) pst-traumatic arthrsis, 4% (1/23) pli, 4% (1/23) fibular hemimila and 4% (1/23) achndrplasia. Adjunctive surgical prcedures dne tgether with ankle distractin: 22 anterir ankle stephyte resectins, 8 supramallelar stetmies, 7 lengthening f the Achilles tendn, 3 tarsal tunnel decmpressins, 9 cre decmpressins f the talus/tibia, 6 hardware remvals, 1 fascitmy, 1 plantar fascial release, 1 prximal tibial lengthening, 2 gradual equinus crrectins, 3 psterir ankle stephyte resectins and 2 hindft defrmity crrectins. 48 % (11/23) f patients received a series f 3 grwth hrmne injectins (10 mg per intra-articular ankle injectin) during the treatment. 9% (2/23) f patients had previusly been treated by ankle distractin with the same prtcl and pted fr a secnd treatment. One patient had relief fr 4 years and the ther 1 fr 2 years befre reattempting distractin. Other issues: Nne. IP verview: jint distractin fr ankle stearthritis Page 19 f 41

20 Key efficacy and safety findings Efficacy Number f patients analysed: 18 (respnders t the questinnaires) Average duratin f treatment with external fixatin: 17 weeks. Ttal arc f ankle jint mtin befre the prcedure (mean): 28º Ttal arc f ankle jint mtin after the prcedure (mean): 27º Safety Cmplicatins during distractin Cmplicatin Incisin and drainage f an external fixatin pin site Incisin and drainage f the anterir ankle incisin site Number f episdes 1 1 Cnversin t ther ankle surgery % f patients treated by anther ankle prcedure: 11% (2/18) 1 patient was treated by ankle fusin 1 patient was treated by ankle replacement Authrs reprted that apprximately 75% f patients needed at least 1 curse f antibitics during the distractin treatment (further details nt given). Ft and ankle questinnaire At mean 64 mnths f fllw-up, Mean scre: 71 (range 44-98)* Mean scre in the grup with 5 years r less f fllw-up (n=9): 79* Mean scre in the grup with mre than 5 years f fllw-up (n=9): 52* N significant difference fr pain between the grup with 5 years r less f fllw-up and the grup with mre than 5 years f fllw-up (p=0.187). Mean she cmfrt scre: 47** * Scre frm 0 t 100 (pr utcme t best pssible utcme). ** Scre frm 0 t 100 (100= n discmfrt). Pain Patients taking pain killers such as NSAIDs ccasinally fr ankle pain: 61% (11/18) f patients Patients with nly ccasinal mderate-t-mild ankle pain: 78% (14/18) Ability t walk 77% f patients said they walked fr pleasure 33% f patients said they culd run 22% (4/18) f patients used an assistive device t walk 11% (2/18) f patients reprted severe limitatins. Patient satisfactin Patients very satisfied r satisfied by the result f the prcedure: 61% (11/18) Patients nt satisfied with the utcme: 33% (6/18) Patients wh wuld recmmend this prcedure t a friend: 71%. Abbreviatins used: NSAIDs, nn-steridal anti-inflammatry drugs; OA, stearthritis; IP verview: jint distractin fr ankle stearthritis Page 20 f 41

21 Study 7 Intema F (2011) Details Study type Case series (patients frm the Saltzman 2012 study included in table 2) Cuntry USA Recruitment perid Study ppulatin and number Age and sex Patient selectin criteria n=26 patients with severe pst-traumatic ankle OA. Mean 41 years; 65% (17/26) male Selectin criteria: symptmatic islated, unilateral Kellgren-Lawrence (KL) grade 3 r 4 ankle OA, skeletally mature and age 60 years, failure f nn-perative treatment > 1 year, and capacity t maintain extremity nn-weight-bearing using ambulatry aids. Excluded criteria: patients with histry f inflammatry arthritis, the presence f ther symptmatic jints n the ipsilateral lwer extremity, cntralateral ankle arthritis (KL grade 2 4), ankle r hindft malalignment, patients living greater than 300 miles away frm treatment centre, current histry f alchl r drug abuse. Technique Same as in Saltzman (2012). Fllw-up Cnflict f interest/surce f funding 24 mnths after frame remval The study was financially supprted by grants frm the Natinal Institutes f Health/ Natinal Institute f Arthritis and Musculskeletal and Skin Diseases. Analysis Fllw-up issues: Initially, 40 patients were included in the Saltzman study. Suitable CT scans were unavailable fr 35% f patients (14/40) (5 patients withdrew, 1 fused befre 1 year f fllw-up, 3 CT scans had severe metal artefacts, and 5 baseline CT scans had technical errrs). Duble-cntrast (systemically and intra-articular) axial CT scans were btained at baseline (befre treatment), and at 1- and 2-year fllw-up after treatment t analyse jint space width and bne density. Study design issues: Changes in bne density (in Hunsfield Units (HU), measured relative t baseline) were queried at ver discrete lcatins beneath the tibial and talar weight-bearing regins. The measurement grid cvered a subchndral patch f nminally 650 mm2, with typically 4000 pint measurements per surface (~0.17 mm 2 /pint). Bne density was measured at 1 mm intervals beneath the bne surface, alng the surface nrmals and extending subchndrally up t 8 mm. Baseline and fllw-up data fr bne density at 1 t 8 mm frm jint surface shwed a nrmal distributin and parametric statistics were applied. Statistical significance in changes ver time were determined using the paired samples T-test (the data at baseline and fllw-up per patient served as a pair). Clinical data als shwed nrmal distributin and significant imprvement was determined by using the paired samples T-test. Spearman crrelatins f the sum f change in bne density fr tibia and talus (mean change per pint in high and lw density areas) were used t identify significant crrelatins with clinical imprvement (percentage change cmpared t baseline). Study ppulatin issues: Same patients as in Saltzman (2012) study. Other issues: Nne. IP verview: jint distractin fr ankle stearthritis Page 21 f 41

22 Key efficacy and safety findings Efficacy Number f patients analysed: 26 Safety Nt reprted. Change in bne density ver the area f 1 t 8 mm frm the jint surface frm baseline (mean ± SD) At 1-year fllw-up Tibia: -23±12% (p<0.001) Talus: -18±15% (p<0.001) At 2-year fllw-up Tibia: 21±12% (p<0.001) Talus: 16±15% (p<0.001) Change in bne density (mean±sd in HU, 95% CI) cmpared against baseline fr tibia and talus at 1 and 2 years f fllw-up. 1-3 mm beneath jint surface > 400 HU at baseline 1 year 2 years Mean±SD 95% CI Mean±SD 95% CI Tibia 237± t ± t -139 Talus 156± t ± t -101 < 400 HU at baseline Tibia 123± t ± t mm beneath jint surface Talus 41±111 3 t 84 58±114 9 t 107 > 400 HU at baseline Tibia 184± t ± t -147 Talus 138± t ± t -93 < 100 HU at baseline Tibia 144± t ± t 212 Talus 92± t ± t 140 AOS pain (mean±sd) Baseline: 60±3% f the maximum scre At 1-year fllw-up: 35±4% f the maximum scre, p<0.001 versus baseline At 2-year fllw-up: 35±5% f the maximum scre, p<0.001 versus baseline AOS disability (mean ± SD) Baseline: 67±2% f the maximum scre At 1-year fllw-up: 46±5% f the maximum scre, p<0.001 versus baseline At 2-year fllw-up: 36±5% f the maximum scre, p<0.001 versus baseline Abbreviatins used: AOS, ankle stearthritis scale; CI, cnfidence interval; CT, cmputerised tmgraphy; HU, Hunsfield Units; KL, Kellgren-Lawrence; SD, standard deviatin IP verview: jint distractin fr ankle stearthritis Page 22 f 41

23 Study 8 Tellisi N (2009) Details Study type Cuntry Case series USA Recruitment perid Study ppulatin and number Age and sex Patient selectin criteria Technique Fllw-up Cnflict f interest/surce f funding n=25 patients with painful ankle arthritis and significant ankle jint mbility (mre than 20º) Mean 43 years; 64% (16/25) male Inclusin criteria: patients with painful ankle arthritis and significant ankle jint mbility (mre than 20º) wh were recmmended ankle arthrdesis treatment t relieve their pain. Exclusin criteria: patients with very limited ankle mbility and patients with severely distrted intra-articular gemetry. Tw weeks after the prcedure, sutures were remved and X-rays were taken t measure the amunt f distractin in the jint. All prcedures were dne by 1 surgen in 1 centre. All patients were treated by spinal anaesthesia. During the prcedure, the ankle was distracted abut 5 mm. Patients were admitted t the hspital after the prcedure fr pain cntrl and 24 hurs f IV antibitics. Prphylactic ral antibitics were started nce IV antibitics had cmpleted and were cntinued fr 10 days. Patients started weight bearing as tlerated immediately after the prcedure. DVT prphylaxis was implemented after 24 hurs and cntinued fr 3 weeks r until patients were very mbile. Pin care (cnsisting f cleaning the pin sites nce daily with diluted hydrgen perxide) was started 2 days after the prcedure. Patients were allwed t shwer and wet the frame and wunds after 4 days. If the jint space was less than 5 mm, additinal distractin was applied in rder t reach 5 mm f jint space. The frame was remved after 12 weeks under sedatin. After frame remval, a cam walker bt was applied and weight bearing as tlerated ambulatin was encuraged. In cases f adjuvant supramallelar stetmy, the ft ring was remved after 12 weeks in the ffice if the stetmy had nt fully healed. This ended the distractin perid. The remainder f the fixatr was remved in the perating rm when there was adequate healing at 16 weeks. Mean 30.5 mnths after frame remval Nne reprted. Analysis Fllw-up issues: 92% (23/25) f patients had cmplete data. Patients had fllw-up visits at 2, 6 and 10 weeks. Study design issues: Retrspective study. Study ppulatin issues: Etilgy f ankle OA: pst-traumatic OA fr all patients. Patients treated by adjuvant prcedures: 20% (5/25) Achilles tendn lengthening, 16 % (4/25) ankle arthrscpy, 4% (1/25) pen arthrtmy, and 24% (6/25) supramallelar tibial and distal fibular stetmy t crrect distal tibial defrmity. Other issues: Nne. IP verview: jint distractin fr ankle stearthritis Page 23 f 41