Isolated and Spontaneous Correction of Proximal In

Authors: Michael J Hayton Ardeshir Bayat Douglass S Chapman Robert A Gerber Piotr P Szczypa

Publish Date: 2013/10/05

Volume: 33, Issue: 12, Pages: 905-912

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Abstract

Dupuytren’s contractures affecting proximal interphalangeal PIP joints are challenging to treat We explored the effects of collagenase Clostridium histolyticum CCH on PIP joint contractures after injection of an affected metacarpophalangeal MP joint in the same finger and after injection of an isolated PIP joint contractureTwo patient subsets were evaluated those with MP/PIP joints contractures in the same finger but only the MP joint contractures were treated Group A and those with isolated PIP joint contractures that were treated Group B Endpoints included correction and improvement in contracture Fixedflexion contracture FFC and range of motion ROM were also assessed adverse events AEs were monitoredIn Group A 28 and 43  of PIP contractures spontaneously corrected after the first and last injection of CCH respectively for MP contractures 40 and 63  respectively improved In Group B 31 and 39  of PIP joint contractures corrected after the first and last injection of CCH respectively 56 and 66  respectively improved In Groups A and B FFC improvements were largest after the last injection ROM improvements were largest after the last injection in Group A and third injection in Group B For 46 and 44  of patients in Groups A and B respectively the first injection was the last injection In Group B the median minimum maximum injections/joint was 10 10 40 Nearly all patients 98  experienced ≥1 AE most were injectionsite reactionsIn Dupuytren’s disease the metacarpophalangeal MP proximal interphalangeal PIP and distal interphalangeal DIP joints can develop fixedflexion deformities due to the development and subsequent contraction of diseased cords in the affected tissue Although PIP joints are not affected as often as are MP joints 1 they can be more disabling for patients as many routine daily activities are impaired when these joints are contracted 1 2 Frequently PIP joint contracture is accompanied by MP joint contracture 3 Research has shown that improvements in PIP joint contractures correlate positively with improved hand function 2 4 The PIP joint contractures are also more challenging to treat using corrective surgery 5 6 or minimally invasive procedures such as percutaneous needle fasciotomy PNF 2 and collagenase Clostridium histolyticum CCH injections 7 The CCH injection is the first nonsurgical pharmacologic treatment for Dupuytren’s contracture DC with a palpable cord approved for use in the USA and Europe Clinical trials 7 8 9 and postmarketing studies 10 11 have demonstrated the efficacy and safety of CCH for correcting DCCORD Collagenase Option for Reduction of Dupuytren’s I 8 and II 7 were 90day phase III trials conducted at 16 sites in the USA and five sites in Australia respectively CORD I also had a 9month openlabel extension JOINT I and II were 9month openlabel studies conducted at 14 sites in the USA and 20 sites in Europe and Australia respectively 9 For all four studies eligible patients aged ≥18 years were required to have a fixedflexion deformity in ≥1 finger other than the thumb that was ≥20° and ≤100° in an MP joint or ≥20° and ≤80° in a PIP joint caused by a palpable cord that had not been previously treated with CCHBefore treatment in all four studies investigators selected the hand to be treated and prioritized all palpable cords as primary secondary and tertiary The primary cord could affect an MP or PIP joint if the contracture occurred solely in these respective joints If there were contractures in both the MP and PIP joints of the same finger the cord causing the MP contracture was deemed the primary cord After the primary joint was successfully treated either an MP or PIP joint contracture could be selected Subsequent joints were selected on the basis of providing the patient with full functionality of the treated hand Patients could receive a maximum of three injections during the study period The primary endpoint was clinical success defined as a reduction in contracture of the primary joint to ≤5° of full extension 30 days after injection Secondary endpoints included clinical improvement defined as a ≥50  reduction in contracture of a treated joint and a spontaneous effect of treatment defined as a ≥20° reduction in contracture of any other joint not directly treated with CCH Changes in fixedflexion contractures FFC and range of motion ROM were also assessed

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