Dr. Tina Brar of SIMEDHealth's Arthritis Center recently wrote an article for House Calls Magazine, a seasonal publication for the Alachua County Medical Society. The following article discusses advances in the treatment of psoriatic arthritis. 

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Article content:

Introduction
Although  psoriasis  has  been  described  since  the  time of   Hippocrates,   psoriatic   
arthritis   was   identified   as   a separate disease entity in the 1960s by what is now the 
American College of Rheumatology (ACR).  Initially thought to  be  benign,  it  is  now  recognized 
 as  a  member  of  the spondyloarthropathies  and  is  a  debilitating,  progressive illness with 
a comparable impact on functional ability and quality of life as rheumatoid arthritis (RA).  Early 
diagnosis is  imperative  to  prevent  long-term  disability  and  ensure optimal management of the 
disease and its comorbidities.

Psoriatic   arthritis   (PsA)   is   a   complex   affliction   with musculoskeletal involvement- 
including arthritis, dactylitis, enthesitis and/or axial involvement as well as skin and nail 
disease.   Although the exact pathogenesis is not known, it is thought that genetic, immunologic 
and environmental factors play a role.   The prevalence of PsA in the United States  is  around  
0.25%,  however  about  30%  of  patients with psoriasis also have psoriatic arthritis, affecting 
men and women equally.   It is therefore prudent to screen all psoriasis patients for PsA.  Varying 
patterns of the disease mimic different inflammatory conditions, such as gout and RA.  
Approximately 15% of patients develop arthritis prior to skin involvement, making the diagnosis 
difficult.  Generally, laboratory tests are unhelpful as there is no specific test for PsA and 
systemic inflammatory markers may be elevated in only half the cases.  The genetic marker HLA-B27 
is not a diagnostic test as no more than 2% of people born with this  gene  will  eventually  
develop  a  spondyloarthropathy. A    multidisciplinary    approach    between    dermatology and  
rheumatology  is  helpful  in  analyzing  many  cases. Recognition of this disease process has 
increased with the introduction of the classification criteria, CASPAR, as well as the development 
of several screening tools that allow for timely intervention.

Treatment

Anecdotally,  treatment  options  for  PsA  were  limited  to non-steroidal    anti-inflammatory    
drugs    (NSAIDs)    and conventional    disease-modifying    anti-rheumatic    drugs (DMARDs).  
Initially developed to treat rheumatoid arthritis, these   medications   have   varying   benefits  
 in   treating inflammation and the vast manifestations of PsA as well. Multiple systematic reviews 
have determined that the effect size of these DMARDs such as methotrexate, sulfasalazine and 
leflunomide are not very high and cyclosporine is seen as  toxic.   Corticosteroids  can  be  used  both 

locally  as injections and systemically, although not supported by evidence-along  with  the  concern

  of  rebound  psoriasis upon withdrawal of the drug.

Spanning  the  past  decade,  the  availability  of  targeted synthetic   and   biologic   DMARDs   
has   revolutionized treatment.    Given  these  advances,  a  “treat-to-target” approach  towards  
management  has  been  proposed, following  its  favorable  application  in  other  rheumatic 
conditions.     The  ultimate  objective  of  therapy  is  to procure the lowest possible level of 
disease activity in all aspects of the illness.  Despite a lack of cure, there are now effective 
treatments.

Tumor necrosis factor inhibitors (TNFi), which block the inflammatory  mediator  TNF-α,  have  been 
 around  for over  two  decades  and  have  established  breakthrough efficacy in patients with 
PsA. Five TNFi are now available, including adalimumab, etanercept, infliximab, golimumab and  
certolizumab.   Along  with  improvement  in  clinical signs  and  symptoms,  these  treatments  
also  decrease radiographic evolvement of disease.  All TNF-α blockers have been studied in 
randomized control trials as well as  in  observational  studies  with  consistent  evidence 
supporting  their  efficacy  and  safety  in  PsA.   Currently, trial  data  is  limited  in  
regards  to  switching  from  one inhibitor to another, although clinically it is a successful 
strategy.    The  choice  of  agent  is  based  upon  patient preference as well as regulatory and 
payor requirements and/or limitations

In  recent  years,  new  biologics  with  alternative  modes of  action  have  also  been  tested  
and  approved  in  PsA. Ustekinumab  is  an  FDA  approved  IL  12/23  inhibitor with  evidence  in 
 treating  arthritis,  skin,  enthesitis  and dactylitis. Guselkumab, an IL-23 blocker, is 
currently FDA approved for psoriasis only and is under investigation for the management of PsA with 
promising data.

Research  now  highlights  the  importance  of  the  TL- 17  pathway  and  a  number  of  therapies 
 targeting  this pathway  are  being  studied.    FDA  approved  anti-IL-17 therapies    include    
secukinumab    and    ixekizumab. Currently  brodalumab  is  FDA  approved  for  psoriasis only, 
but has shown efficacy in trials for PsA as well.
Tofacitinib  is  an  oral  inhibitor  of  Janus  kinase  that has  demonstrated  efficacy  in  the  treatment  of  PsA  in several  randomized  trials  including patients  with  both an  inadequate  response  to  conventional  DMARDs  and TNFα(alpha) to inhibitors.

Abatacept,   a   selective   T-cell   costimulation   modulator used  in  the  treatment  of  
rheumatoid  arthritis,  has  also shown  benefit  in  patients  with  PsA  in  limited  published 
randomized  trials  and  therefore  became  FDA-approved last year.

Apremilast,  a  phosphodiesterase  4  inhibitor,  is  a  newly targeted   synthetic   DMARD   that  
 induces   suppression of  several  inflammation  mediators  including  IL-2,  IL-12, TNF-α, IFN-γ 
and inducible nitric oxide synthase. Efficacy and  safety  in  PsA  has  been  demonstrated  
through  four multi-centric, randomized trials (PALACE Trials) compared to placebo in patients who 
failed other biological options.

Unfortunately,   evidence-based   guidelines   to   navigate
how these therapies should be used are lacking.   Several 
international   and   national   recommendation   sets   are created such as GRAPPA (figure 1) and 
EULAR, with the aim to help rheumatologists in everyday clinical practice management.     At  this  
time,  drug  choices  are  made according  to  available  safety  data,  presence  of  extra- 
articular  manifestations,  cost  and  patient’s  preference. Information  directly  comparing  all 
 biological  drugs  and assessing the efficacy of treatment options specific for PsA  is urgently 
needed.

Conclusion
The  hope  is  that  in  the  future  PsA  patients  will  be treated earlier and more aggressively 
with targeted drug therapies to escape marked progression of joint damage. Moreover, with effective 
management of the skin and joint disease as well as the  consideration  of  risk  factors for 
comorbidities, it will be reasonable to expect to improve the quality of life and function in these 
patients.

References available upon request.