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Early Combined Treatment with Biologic and Conventional DMARDs

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Patients started on early, aggressive treatment with a combination of biologic and conventional disease modifying antirheumatic drugs (DMARDs) achieved clinically inactive disease in children. Image for illustration purposes.

Mega Doctor News

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by American College of Rheumatology (ACR)

Newswise — ATLANTA  — New research  presented  this  week  at  ACR  Convergence,  the  American  College of  Rheumatology’s  annual  meeting,  found  that  patients  started  on  early,  aggressive  treatment with  a  combination  of  biologic  and  conventional  disease  modifying  antirheumatic  drugs (DMARDs)  achieved clinically  inactive disease in  children  with  polyarticular  juvenile idiopathic arthritis  (JIA)  more  frequently  compared  to other  treatment  plans  24 months  after  starting treatment  (Abstract  #0960).  

Polyarticular  JIA  affects  five  or  more  joints  and  can begin at  any  age.  The  overall  treatment  goal for polyarticular  JIA  is  to control  symptoms,  prevent  joint  damage,  and maintain  function.  Some children  may  achieve  clinical  inactive  disease with  treatment.

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The study  compared three  consensus  treatment  plans,  or  CTPs,  for polyarticular  JIA  that  were originally  developed  by  the  Childhood  Arthritis  and  Rheumatology  Research Alliance (CARRA) to see  which  one was  most  effective at  achieving  clinically  inactive  disease in  previously untreated  patients.  These researchers  previously  reported  the primary  outcomes  after  121 months,  and  now,  they  are  reporting  outcomes  for  patients  after  24  months  of  follow-up.  

“The  goal  of  our  trial  was  to  compare  the  three  CARRA  consensus  treatment  plans  to  determine whether  the  timing  of  when  biologics  were  started is  important  in the  overall  outcomes  in untreated  polyarticular  JIA,  using  a  non-randomized  observational  study  design,”  says  Yukiko Kimura,  MD,  Chief,  Division  of  Pediatric  Rheumatology,  at  Hackensack  University  Medical Center  in  New  Jersey,  and  the  study’s  co-author.  “It’s  crucial  to  look  at  longer  term  outcomes because  these  allow  us  to  learn  about  how  initial  treatment  might  affect  damage  and  chronic disability,  which  only  occur  over  years.  We  can  also  learn about  continuing  disease  control, quality  of  life  and  whether  remission on  and  off  medications  might  be  possible.”

Three  standardized  CTPs  were  compared in  the  study,  which  originally  enrolled  400  patients:

•  Step  Up:  starting  a  conventional  synthetic  DMARD  then  adding  a  biologic  if  needed  after three  or  more months;  

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•  Early Combination:  starting  patients  on  a  conventional  synthetic  and  biologic  DMARD together;  

•  Biologic  First:  starting  a  biologic  DMARD  alone and  adding  a  conventional  synthetic DMARD after  three  or  more  months  if  needed.

Patients  were  not  randomized.  Researchers  collected  data  every  three  months  for  the  first  12 months,  then  every  six  months  using  the  CARRA  Registry.  Although the  primary  study  ended  at 12 months,  the  Registry  continues  to follow  every  patient  for  at  least  10  years,  allowing  longerterm  outcomes  to be  analyzed.  The  primary  outcome  measured  was  the proportion of  children achieving  clinical  inactive  disease  off  glucocorticoids  at  24  months.  Secondary  outcomes  were the  clinical  Juvenile  Arthritis  Disease  Activity  Score  based on  10  joints,  the  Pediatric  ACR  70 disease  activity  score,  and  patient-reported  outcomes.

There  were  291  patients  who  completed  their  24-month  clinic  visit:  188  on Step  Up,  76  on  Early Combination  and  27  on Biologic  First.  There  were  some  significant  baseline  differences between  the  groups,  including  the  number  of  actively  inflamed  joints  and  disease activity  scores. At  24  months,  52%  of  patients  on  Early  Combination  achieved  clinical  inactive  disease, compared with 42%  of  patients  on  Step  Up and  44%  on  Biologic  First.  There  was  a  significant difference  in  clinical  inactive disease  outcomes  that  favored  Early  Combination  CTPs  over  Step Up at  24  months  of  treatment,  but  there  were  no  significant  differences  between  the three  plans for  other  study  outcomes.

Researchers  found  that  all  3  groups  continued  to  improve  at  24  months  compared to  their outcomes  at  12  months,  including  the  clinical Juvenile  Arthritis  Disease  Activity  Score  and  the Pediatric  ACR  70  disease  activity  score.  Patients  in  all  3 groups  also  showed  improvement  in pain  interference  and joint  mobility  measures  from  baseline.  There were  17  adverse  events reported in the  study,  most  commonly  infections.  

“It’s  encouraging that  in  general,  most  polyarticular  JIA  patients  are  doing  well  at  24  months when  treated  initially  with  effective  medications.  These  results  suggest  that  early  treatment  with biologics  in  combination  with  conventional  DMARDs  may  be the  most  effective  strategy  in  the long  term  for  many  patients,” says  Dr.  Kimura.  “We  will  continue to study  this  patient  cohort  over longer  periods  of  time  and  perform  other  analyses  on  this  data  to better  understand  CTP effectiveness.  Polyarticular  JIA  is  still  a  challenging disease  that  continues  to  need  better treatment  options  and  a  more personalized  approach  to  optimize  outcomes.”

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