Treatment of Acute Pericarditis With Anakinra
Phase: PHASE2
Conditions: Acute Pericarditis
Sponsor: Virginia Commonwealth University

 
 
Title: Treatment of Acute Pericarditis With Anakinra 
 
NCT #: NCT03224585 
 
Document approval date: June 8, 2017 
 
Document Type: Protocol 
 
 
 

TREATMENT OF ACUTE PERICARDITIS WITH ANAKINRA: A PILOT STUDY 
Acute pericarditis is a clinical syndrome characterized by an inflammation of the pericardial layers1-2. It can be 
caused by a variety of infectious and non-infectious agents, but it most commonly either follows a viral infection 
of the upper respiratory tract (when the virus is gone) or has no apparent cause, in which case it is referred to 
as idiopathic1-2. Acute pericarditis occurs rather abruptly in previously healthy individual, generally a child or 
young adult. While the prognosis of acute pericarditis is favorable, with most cases resolving within few days, it 
is associated with chest pain and discomfort, often severe and requiring an escalation of therapy, and it is 
occasionally associated with life-threatening complications, such as pericardial tamponade – hypotension and 
shock due to impaired cardiac filling secondary to large pericardial effusion1.  
Acute pericarditis is diagnosed in 1 in 20 (5%) ED visits for chest pain, 1 in 1,000 (0.1%) hospital admissions, 
and in 1 in 10,000 (0.01%) healthy individuals1, reflecting a significant clinical burden worldwide.  
The pathophysiology of acute pericarditis is a stereotypical 
response to an acute injury to the mesothelial cells constituting the 
pericardial layers around the heart. The inflammation is initiated by 
an ‘irritant’ which can be the virus itself or the release of cellular 
debris3-5. The response is however sustained by an amplification of 
the injury through the activation of the Nod-like receptor 3 (NLRP3) 
inflammasome, 
an 
intracellular 
macromolecular 
structure 
responsible for sensing danger or injury and intensifying the 
inflammatory response through the release of mature Interleukin-
1β (IL-1β)3-5. IL-1β is indeed an apical pro-inflammatory cytokine 
that stimulates the synthesis of inflammatory mediators such as 
cyclo-oxygenase-2 (COX-2), prostaglandins and subsequent 
hyperemia, edema, and hyperesthesia characteristic of the acute 
pericarditis syndrome (Figure 1)6. In most instances, by the time the 
subject presents with chest pain, the initial insult can no longer be 
identified, and all that is seen in the inflammatory response.  
Anti-inflammatory therapy has been the mainstay of the treatment 
for acute pericarditis, yet there are no drugs indicated and/or 
approved by the Food & Drug Administration specifically for the treatment of acute pericarditis, and the 
treatments conventionally used are associated with rate limiting side effects or high rate of recurrences1-2. Non-
steroidal anti-inflammatory drugs (NSAIDs) are the most commonly used first line treatment. The anti-
inflammatory activity of NSAIDs is related to the inhibition of COX-2 and reduction in prostaglandins synthesis, 
resulting in local control of pain (Figure 1). NSAIDs (such as indomethacin, diclofenac, ibuprofen) are generally 
effective in controlling symptoms but these drugs significantly increase risk of gastro-intestinal bleeding, 
hypertension and renal failure, and are associated with a significant recurrence rate after discontinuation of 
treatment. Colchicine is used as a second line drug, and is also highly effective by inhibiting tubulin aggregation 
and NLRP3 inflammasome formation. Colchicine however is associated with a 15-20% discontinuation due to 
diarrhea and other gastrointestinal discomforts7, and, although rarely, also with bone marrow suppression (Table 
1). 
Glucocorticoids 
(such 
as 
prednisone) are rarely used in 
acute pericarditis because although 
very effective in controlling acute 
pericarditis by inhibiting NF-kB 
signaling, these drugs increase risk 
of 
gastro-intestinal 
bleeding, 
hypertension, 
and 
are 
also 
associated with a higher recurrence 
rate. In some rare cases, acute 
pericarditis is secondary to another 
disease 
such 
as 
bacterial 
pneumonia, cancer invading the 
pericardium, tuberculosis, connective tissue diseases – in such cases treatment is aimed at the underlying 
disease. While anti-inflammatory drugs relieve pain in all types of pericarditis, elimination of the offending agent 
is essential for healing. 
Injury&
Pro-IL-1β&
NLRP3&inﬂammasome&
IL-1β&
COX-2&
Prostaglandins&
NSAIDs&
(ibuprofen)&
Colchicine&
Anakinra&
gure 1. Pathophysiology of acute pericarditis: 
an injury due to an infectious or non-infectious 
pathogen triggers the formation of the NLRP3 
inflammasome initiating a local and systemic 
ammatory response.  
Treatment 
Advantage(s) 
Disadvantage(s) 
Non-steroidal anti-
inflammatory drugs 
(NSAIDs)[i.e. ibuprofen] 
Highly efficacious in relieving pain 
Increased blood pressure, sodium/
water retention, risk of bleeding 
Colchicine 
Greater response rate when added to 
NSAIDs, prevents recurrences when 
added to NSAIDs 
Gastrointestinal intolerance (15-25%); 
bone marrow suppression (rare) 
Glucocorticoids  
[i.e. prednisone] 
Preferred in cases of connective tissue 
diseases 
Impaired glucose control, increased 
blood pressure, sodium/water 
t
ti
i k f
ti
l
di

 
 
Pil ot st u dy of A n aki nr a  f or ac ut e p eric ar ditis  
V ersi o n 2  
T h er e i s a cl e ar n e e d t o d e v el o p n o v el t h er a pi e s f or a c ut e p eri c ar diti s . 
 
I N N O V A TI O N: 
A s r e pr e s e nt e d i n Fi g ur e 1, N L R P 3  a n d I L- 1b  o c c u p y  a c e ntr al r ol e of i n t h e p at h o g e n e si s of a c ut e p eri c ar diti s: 
a cti v ati o n  of t h e N L R P 3 i nfl a m m a s o m e  l e a d s t o r el e a s e of m at ur e I L- 1b , s y nt h e si s of C O X - 2 a n d  pr o st a gl a n di n s 
a n d s u b s e q u e nt h y p er e mi a a n d p ai n.  S u bj e ct s wit h  s p e cifi c  m ut ati o n s i n t h e Nlr p 3  ( al s o k n o w n a s cr y o p yri n) , 
r e n d eri n g it c o n stit uti v el y a cti v e, e x p eri e n c e s p o nt a n e o u s b o ut s of s y st e mi c i nfl a m m ati o n – cr y o p yri n -a s s o ci at e d 
p eri o di c s y n dr o m e s [ C A P S] 8- 9 - w hi c h ar e e x q ui sit el y r e s p o n si v e t o I L - 1b  bl o c k er s. T h e cli ni c al m a nif e st ati o n s of 
C A P S  v ar y  fr o m  mil d  t o  s e v er e  s y st e mi c  i nfl a m m ati o n,  wit h  a c ut e  p eri c ar diti s b ei n g  o n e  of  t h e  m or e s e v er e 
cli ni c al pr e s e nt ati o n s 1 0 -1 1 . T h e s e r ar e c a s e s of g e n eti c all y m ut at e d Nlr p 3  hi g hli g ht t h e i m p ort a n c e of N L R P 3 i n 
a c ut e  p eri c ar diti s .  A n ot h er  r el ati v el y u n c o m m o n  s y n dr o m e  wit h  f a mili ar  tr a n s mi s si o n  i s r e c urr e nt  i di o p at hi c 
p eri c ar diti s  – a s y n dr o m e of i s ol at e d r e c urr e nt a c ut e p eri c ar diti s o n a n a ut o -i nfl a m m at or y b a si s, a n d alt h o u g h 
t h e g e n e( s) i n v ol v e d ar e u n k n o w n, idi o p at hi c p eri c ar diti s i s al s o r e s p o n si v e t o I L - 1b  bl o c k er s 1 2 . M o st c a s e s of 
p eri c ar diti s ar e h o w e v er  a c q uir e d a n d , g e n er all y, r el at e d t o re c e nt  vir al i nf e cti o n s. Eit h er t h e tr a n si e nt i nf e cti o n 
of  t h e  p eri c ar di al c ell s  b y  t h e  vir u s( e s) or  t h e  i nj ur y  r el at e d  t o  t h e  i nf e cti o n l e a d s  t o  a cti v ati o n  of  t h e  N L R P 3 
i nfl a m m a s o m e  a n d  t h e  N F-k B  a n d  C O X 2 -d e p e n d e nt  i nfl a m m ati o n ,  w hi c h  l e a d s  t o  a  f ull bl o w n  a c ut e 
i nfl a m m at or y r e s p o n s e t h at i s at t h at p oi nt ‘ st eril e’ – fr e e of vir u s( s). T h e cli ni c al s y n dr o m e of p ai n a n d di s c o mf ort 
i s r el at e d t o t h e st eril e i nfl a m m at or y r e s p o n s e . Th e  b e n efi ci al  eff e ct s  of N S AI D s ar e m e di at e d t hr o u g h  i n hi biti o n 
of C O X - 2 a n d r e d u cti o n i n pr o st a gl a n di n pr o d u cti o n 1- 2 . M or e r e c e ntl y c ol c hi ci n e h a s b e e n s h o w n t o b e eff e cti v e 
i n  a c ut e  p eri c ar diti s1 3 .  T h e  r e n e w e d  i nt er e st  i n  c ol c hi ci n e  a s  a nti-i nfl a m m at or y  t h er a p y  i n  a c ut e  i nfl a m m at or y 
di s e a s e  d eri v e s  fr o m it s u s e  a s  a  tr e at m e nt  o f g o ut y  art hriti s .  T hi s h a s  l e d  t o  a  b ett er  u n d er st a n di n g  of t h e 
m e c h a ni s m of a cti o n
1 4 -1 5 . I n vitr o st u di e s n o w li n k it t o t h e N L R P 3 i nfl a m m a s o m e, c ol c hi ci n e i n hi bit s  mi cr ot u b ul e 
f or m ati o n  a n d i nt erf eri n g wit h  t h e  f or m ati o n  of  t h e  m a cr o m ol e c ul ar  str u ct ur e c o m p o s e d  of A S C  ( a p o pt o si s -
a s s o ci at e d s p e c k -li k e pr ot ei n c o nt ai ni n g a c a s p a s e r e cr uiti n g d o m ai n), N L R P 3, pr o -c a p a s e -1 a n d  pr o -I L- 1b , a n d 
h e n c e pr e v e nti n g  a cti v ati o n of t h e N L R P 3 i nfl a m m a s o m e a n d t h e r el e a s e of a cti v e I L - 1b 1 4 -1 5 . W hil e eff e cti v e i n 
m a n y c a s e s , c ol c hi ci n e i s li mit e d b y d o s e-d e p e n d e nt si d e eff e ct s, m ai nl y g a str oi nt e sti n al 7 . I L- 1b  bl o c k er s  ar e  
hi g hl y  eff e cti v e  i n  tr e ati n g  a c ut e  a n d  c hr o ni c  p er i c ar diti s,  i n cl u di n g  t h o s e  s e v er e  c a s e s  t h at  ar e  r efr a ct or y  t o 
N S AI D s  a n d  t o  c ol c hi ci n e 2 , 1 6-2 5 .  T h er e  ar e  s e v er al  dr u g s  a p pr o v e d  b y  t h e  F D A  a s I L- 1b  bl o c k er s i n cl u di n g 
a n a ki nr a  ( Ki n er et ® ), c a n a ki n u m a b  (Il ari s ® ),  a n d  ril o n a c e pt  ( Ar c al y st ®)  b ut n o n e  ar e  a p pr o v e d f or  a c ut e 
p eri c ar diti s 2 6 -2 7 . 
 
 
D e v el o pi n g  a  a n I L-1  bl o c k er  a s  pr ef err e d  tr e at m e nt  f or a c ut e  p eri c ar diti s  wit h o ut  t h e  si d e  eff e ct s  of  t h e 
c urr e ntl y a v ail a bl e tr e at m e nt s , w o ul d b e of gr e at cli ni c al, a n d c o m m er ci al, i m p a ct .  
 
 
I n  c o n cl u si o n,  th e  c urr e nt  tr e at m e nt  f or  a c ut e  p eri c ar diti s  i s  b a s e d  o n N S AI D s  a n d/ or  c ol c hi ci n e.  W hil e  it  i s 
c o n si d er e d st a n d ar d of c ar e, t hi s str at e g y i s n ot b a s e d o n l ar g e cli ni c al tri al s, a n d f ail ur e of t hi s str at e g y i s k n o w n 
t o o c c ur i n t h e f oll o wi n g t er m s: 1) F ail ur e t o a c hi e v e r e s ol uti o n of s y m pt o m s ; 2) o c c urr e n c e of si d e -eff e ct s li miti n g 
u s e ; 3) e arl y r e c urr e n c e of s y m pt o m s aft er di s c o nti n u ati o n of tr e at m e nt . A n a ki nr a ( ki n er et) h a s b e e n s h o w n t o 
tr e at a n d c ur e r efr a ct or y a n d r e c urr e nt p eri c ar diti s. T hi s st u d y i s ai m e d at d et er mi ni n g w h et h er a n a ki nr a i s al s o 
eff e cti v e a s fir st li n e tr e at m e nt i n a c ut e p eri c ar diti s.  
 
A n a ki nr a i s li k el y t o h a v e a m or e f a v or a bl e ri s k pr ofil e a n d b e m or e eff e cti v e t h a n st a n d ar d of c ar e f or a c ut e 
p eri c ar diti s.  T h e  ri s k  of  a n a ki nr a  u s e  ar e  li mit e d  t o  i nj e cti o n  sit e  r e a cti o n  ( a p pr o xi m at el y  1 0 %  if  tr e at m e nt  i s 
c o nti n u e d f or 2 w e e k s or m or e, l e s s if tr e at m e nt i s gi v e n f or l e s s t h a n 1 w e e k), a r e d u cti o n of s y m pt o m s a n d 
si g n s  of s y st e mi c i nf e cti o n w hi c h m a y l e a d t o a m or e wi d e s pr e a d i nf e cti o n at ti m e of di a g n o si s (t hi s ri s k i s l o w, 
< 5 % p er y e ar wit h c o nti n u o u s tr e at m e nt, a n d i s r e d u c e d b y cli ni c al a w ar e n e s s a n d m o nit ori n g f or c h a n g e s i n 
cli ni c al st at u s).  T h e p ot e nti al b e n efit i s f or a r a pi d a n d s u st ai n e d r e s ol uti o n of a c ut e p eri c ar diti s wit h o ut eff e ct s 
o n r e n al f u n cti o n (i. e. n o n -st er o i d al a nti-i nfl a m m at or y dr u g s), g a str oi nt e sti n al si d e eff e ct s (i. e. c ol c hi ci n e) a n d 
i n cr e a s e d ri s k of bl e e di n g (i. e. n o n-st er oi d al a nti -i nfl a m m at or y dr u g s). 
 
S P E CI FI C AI M S :  
 
 
T o d et er mi n e t h e effi c a c y a n d t ol er a bilit y  pr ofil e  of a n a ki nr a i n a c ut e p eri c ar diti s  
 
•  
St e p  I – A s s e s s m e nt of a c ut e p ai n r eli ef  wit h a n a ki nr a at  6 h o ur s  
  
 
( a d diti o n al tr e at m e nt s all o w e d o nl y a s r e s c u e str at e g y [ > 9 p ai n], N S AI D s di s c o ur a g e d) 
 
•  
St e p  II – A s s e s s m e nt of s u b a c ut e p ai n r eli ef  wit h a n a ki nr a at 2 4 -h o ur  
  
 
 ( a d diti o n al tr e at m e nt s all o w e d, N S AI D s di s c o ur a g e d)  
 

 
 
Pil ot st u dy of A n aki nr a  f or ac ut e p eric ar ditis  
V ersi o n 2  
•  
St e p  III – C o m p ari s o n of 3- d a y v s 7 -d a y  a n a ki nr a tr e at m e nt   wit h a s s e s s m e nt at 7 a n d 3 0 d a y s  
 
   
R a n d o mi z e d d o u bl e d -bli n d e d a s si g n m e nt  ( a d diti o n al tr e at m e nt s all o w e d)  
 
M il e st o n e s f or St e p  I [O p e n l a b el a n a ki nr a ]: 
  
•  
R eli ef of c h e st p ai n wit hi n 6  h o ur s of tr e at m e nt  
o  C o m pr e h e n si v e p ai n a s s e s s m e nt s c al e a n d Vi s u al A n al o g P ai n ( 0 -1 0) s c al e    
•  
Eff e ct s o n E C G ( S T el e v ati o n s c or e)  
•  
N e e d f or r e s c u e p ai n tr e at m e nt  ( o pi oi d s) f or s e v er e i ntr a ct a bl e p ai n 
•  
I nt er v al c h a n g e i n I L-6 l e v el s fr o m b a s eli n e t o 6 h o ur s  
•  
Si d e eff e ct s pr ofil e  
 
M il e st o n e s f or St e p  II [O p e n l a b el a n a ki nr a ]:  
 
•  
R eli ef of c h e st p ai n at 2 4 h o ur s wit h Vi s u al A n al o g P ai n ( 0 -1 0 ) s c al e  
•  
Eff e ct s o n E C G ( S T el e v ati o n s c or e)  
•  
U s e of a d diti o n al a n al g e si c or N S AI D s   
•  
Si d e eff e ct s  pr ofil e  
•  
I nt er v al c h a n g e i n I L-6 l e v el s fr o m b a s eli n e at 2 4 h o ur s  
 
M il e st o n e s f or St e p III [ D ur ati o n of A n a ki nr a tr e at m e nt]:  
 
•  
R eli ef a n d/ or r e c urr e n c e of c h e st p ai n o n d a y  7 a n d 3 0   
o  C o m pr e h e n si v e p ai n a s s e s s m e nt s c al e a n d Vi s u al A n al o g P ai n ( 0 -1 0 ) s c al e  
•  
C h a n g e s i n p eri c ar di al eff u si o n at e c h o c ar di o gr a p h y o n d a y 7 a n d 3 0 v s d a y 1  
•  
Si d e eff e ct s pr ofil e o n d a y 7 a n d 3 0  
•  
R e c urr e n c e r at e l e a di n g t o ur g e nt offi c e vi sit, e m er g e n c y d e p art m e nt vi sit, h o s pit ali z ati o n, or ot h er  
•  
C o m pr e h e n si v e m et a b oli c pr ofil e a n d c o m pl et e c ell c o u nt wit h diff er e nti al o n d a y 7 a n d 3 0  
•  
I nt er v al c h a n g e i n C R P a n dI L-6 l e v el s fr o m b a s eli n e t o d a y 7 a n d 3 0  
 
I n cl u si o n crit eri a:  
 
•  
A g e ≥1 2 y e ar s i n pr e s e n c e of a p ar e nt a bl e t o pr o vi d e c o n s e nt or a g e > 1 8 y e ar s  
•  
Fir st or r e c urr e nt e pi s o d e of a c ut e p eri c ar diti s, d efi n e d a s t h e pr e s e n c e of at l e a st 2 of t h e f oll o wi n g:  
o  C h e st p ai n ( s u g g e sti v e of p eri c ar diti s a n d n ot e x pl ai n e d b y ot h er c o n diti o n ) 
o  P eri c ar di al fri cti o n r u b  o n p h y si c al e x a m  
o  S T -s e g m e nt el e v ati o n a n d/ or P R d e pr e s si o n o n E C G  
o  N e w or w or s e ni n g p eri c ar di al eff u si o n  
•  
P ai n of m o d er at e -t o-s e v er e i nt e n sit y ( p ai n s c or e ≥6 o n a s c al e of 0 -1 0 w h er e 0 i s n o p ai n at all a n d 1 0 i s t h e 
w or st p ai n e v er e x p eri e n c e d) at ti m e o n e nr oll m e nt  
•  
A bilit y t o pr o vi d e w ritt e n i nf or m e d c o n s e nt if 1 8 y e ar s or ol d er or t o pr o vi d e a s s e nt i n pr e s e n c e of p ar e nt al 
c o n s e nt if 1 2 -1 7 y e ar s of a g e  
 
E x cl u si o n crit er ia:   
 
•   
Peri c ar diti s  d u e t o b a ct eri al or f u n g al i nf e cti o n   
•  
P eri c ar diti s d u e t o m ali g n a n c y  
•  
P eri c ar diti s aft er c ar di a c s ur g er y  
•  
T a m p o n a d e or n e e d f or p eri c ar di o c e nt e si s f or di a g n o sti c/t h er a p e uti c p ur p o s e s  
•  
Pr e g n a n c y or br e a stf e e di n g  
•  
H y p er s e n siti vit y t o a n a ki nr a, l at e x or  pr o d u ct s d eri v e d fr o m  E s c h eri c hi a c oli  
•  
C hr o ni c p ai n s y n dr o m e s or c hr o ni c u s e of a n al g e si c dr u g s  
 
M o nit ori n g f or u s e of p ai n m e di c ati o n s  
 
T h e u s e of p ai n m e di c ati o n s will b e cl o s el y m o nit or e d d uri n g t h e st u d y.  
•  
D uri n g t h e fir st 6 h o ur s ( St e p I)- t h e u s e of a d diti o n al p ai n m e di c ati o n s will b e di s c o ur a g e d u nl e s s c o n si d er e d 
a n e c e s s ar y r e s c u e str at e g y f or p ai n e x c e e di n g 9 i n 0- 1 0 p ai n s c al e.  
•  
D uri n g t h e ti m e b et w e e n 6 -2 4 h o ur s ( St e p II)- t h e u s e of a d diti o n al p ai n m e di c ati o n will b e all o w e d, b ut t h e 

 
 
Pil ot st u dy of A n aki nr a  f or ac ut e p eric ar ditis  
V ersi o n 2  
u s e  of  n o n -st er oi d al  a nti -i nfl a m m at or y  dr u g s  will  b e  di s c o ur a g e d.  A d diti o n al  p ai n  m e di c ati o n s  (i. e. 
a c et a mi n o p h e n, tr a m a d ol, o x y c o d o n e, m or p hi n e, or ot h er) will b e c o n si d er e d.  
•  
B et w e e n  d a y  2  a n d  d a y  3 0  ( St e p  III),  t h er e  will  b e  n o  r e stri cti o n  o n  t h e  u s e  of  p ai n  m e di c ati o n s,  b ut  t h e 
s u bj e ct s will b e a s k e d t o r e c or d t h e u s e of all p ai n m e di c ati o n s o n a d e di c at e d di ar y.  
 
S a m pl e si z e  f or St e p s I a n d II : 
 
V i s u al An al o g u e S c al e S c or e  
St a n d ar d 
d e vi ati o n  
A b s ol ut e c h a n g e 
at 6  a n d 2 4  h o ur s  
S a m pl e Si z e  
( P o w er = 8 0 %) 
S a m pl e Si z e  
(P o w er = 9 0 % ) 
8 
3 
-3  
1 0  
1 3  
-4  
7  
8  
2 
-2  
8  
1 1  
-3  
4  
5  
 
Pr o p o s e d s a m pl e si z e : 
 
•  
1 4 s u bj e ct s  
 
R E F E R E N C E S  
1.  A dl er Y, C h arr o n P, I m a zi o M, et al. 2 0 1 5 E S C G ui d eli n e s f or t h e di a g n o si s a n d m a n a g e m e nt of p eri c ar di al di s e a s e s: 
T h e  T a s k  F or c e  f or  t h e  Di a g n o si s  a n d  M a n a g e m e nt  of  P eri c ar di al  Di s e a s e s  of  t h e  E ur o p e a n  S o ci et y  of  C ar di ol o g y 
(E S C) E ur H e art J. 2 0 1 5; 3 6: 2 9 2 1 -2 9 6 4.  
2.  I m a zi o M, G ait a F, L e Wi nt er M. E v al u ati o n a n d Tr e at m e nt of P eri c ar diti s: A S y st e m ati c R e vi e w. J A M A 2 0 1 5; 3 1 4: 1 4 9 8-
1 5 0 6.  
3.  M at u si a k M, V a n O p d e n b o s c h N, L a m k a nfi M. C A R D - a n d p yri n -o nl y pr ot ei n s r e g ul ati n g i nfl a m m a s o m e a cti v ati o n a n d 
i m m u nit y. I m m u n ol R e v. 2 0 1 5; 2 6 5: 2 1 7-2 3 0.  
4.  L at z E, Xi a o T S, St ut z A. A cti v ati o n a n d r e g ul ati o n of t h e i nfl a m m a s o m e s. N at R e v I m m u n ol. 2 0 1 3; 1 3: 3 9 7 -4 1 1.  
5.  T ol d o S, M e z z ar o m a E, M a ur o A G, S all o u m F, V a n T a s s ell B W, A b b at e A. T h e i nfl a m m a s o m e i n m y o c ar di al i nj ur y a n d 
c ar di a c r e m o d eli n g. A nti o xi d R e d o x Si g n al 2 0 1 5; 2 2: 1 1 4 6 -6 1.  
6.  Di n ar ell o C A. I nt erl e u ki n -1 i n t h e p at h o g e n e si s a n d tr e at m e nt of i nfl a m m at or y di s e a s e s. Bl o o d 2 0 1 1; 1 1 7: 3 7 2 0 -3 7 3 2.  
7.  E hr e nf el d M, L e v y M, S h ar o n P, et al . G a str oi nt e sti n al eff e ct s of l o n g-t er m c ol c hi ci n e t h er a p y i n p ati e nt s wit h r e c urr e nt 
p ol y s er o siti s (f a mili al m e dit err a n e a n f e v er). Di g Di s S ci. 1 9 8 2; 2 7: 7 2 3 -7.  
8.  H off m a n H M. H er e dit ar y i m m u n ol o gi c di s or d er s c a u s e d b y p yri n a n d cr y o p yri n. C urr Al l er g y A st h m a R e p. 2 0 0 7; 7: 3 2 3. 
 9.  Br o d eri c k L, D e N ar d o D, Fr a n kli n B S, et al  T h e i nfl a m m a s o m e s a n d a ut oi nfl a m m at or y s y n dr o m e s. A n n u R e v P at h ol. 
2 0 1 5; 1 0: 3 9 5 -4 2 4.  
1 0.  K u e m m erl e -D e s c h n er  J B,  T yrr ell  P N,  K o ett er  I,  et  al.  Effi c a c y  a n d  s af et y  of  a n a ki nr a  t h er a p y  i n  p e di atri c  a n d  a d ult 
p ati e nt s wit h t h e a ut oi nfl a m m at or y M u c kl e -W ell s s y n dr o m e Art hriti s R h e u m.  2 0 1 1; 6 3: 8 4 0- 9.  
1 1.  I n s al a c o  A,  Pr e n ci p e  G,  B u o n u o m o  P S,  et  al.  A  n o v el  m ut ati o n  i n  t h e  CI A S 1/ N L R P 3  g e n e  a s s o ci at e d  wit h  a n 
u n e x p e ct e d p h e n ot y p e of cr y o p yri n -a s s o ci at e d p eri o di c s y n dr o m e s Cli n E x p R h e u m at ol. 2 0 1 4 J a n -F e b; 3 2( 1): 1 2 3 -5.  
1 2.  C a nt ari ni L, I m a zi o M, Bri zi  M G, et al. R ol e of a ut oi m m u nit y a n d a ut oi nfl a m m ati o n i n t h e p at h o g e n e si s of i di o p at hi c 
r e c urr e nt p eri c ar diti s. Cli n R e v All er g y I m m u n ol. 2 0 1 3; 4 4: 6-1 3.  
1 3.  I m a zi o M. C ol c hi ci n e f or p eri c ar diti s. Tr e n d s C ar di o v a s c M e d. 2 0 1 5; 2 5: 1 2 9-1 3 6  
1 4.  T o n g D C, Wil s o n A M, L a yl a n d J. C ol c hi ci n e i n c ar di o v a s c ul ar di s e a s e: a n a n ci e nt dr u g wit h m o d er n tri c k s. H e art. 2 0 1 6 
M ar 1 8 – o nli n e fir st . 
1 5.  L e u n g Y Y, Y a o H ui L L, Kr a u s V B. C ol c hi ci n e --U p d at e o n m e c h a ni s m s of a cti o n a n d t h er a p e uti c u s e s. S e mi n Art hriti s 
R h e u m. 2 0 1 5; 4 5: 3 4 1 -3 5 0.  
1 6.  S c h at z  A,  Tr a n kl e  C,  Y a s s e n  A, et  al .  R e s ol uti o n  of  p eri c ar di al  c o n stri cti o n  wit h  A n a ki nr a  i n  a  p ati e nt  wit h  eff u si v e-
c o n stri cti v e p eri c ar diti s s e c o n d ar y t o r h e u m at oi d art hriti s. I nt J C ar di ol 2 0 1 6; 2 2 3: 2 1 5  
1 7. Pi c c o P, Bri s c a G, Tr a v er s o F, et al . S u c c e s sf ul tr e at m e nt of i di o p at hi c r e c urr e nt p eri c ar diti s i n c hil dr e n wit h I nt erl e u ki n-
1 b  r e c e pt or a nt a g o ni st ( a n a ki nr a): a n u nr e c o g ni z e d a ut oi nfl a m m at or y di s e a s e. Art hriti s & R h e u m ati s m. 2 0 0 9; 6 0: 2 6 4 -
2 6 8.  
1 8. V a s sil o p o ul o s D, L a z ar o s G, T si o uf i s C, et al . S u c c e s sf ul tr e at m e nt of a d ult p ati e nt s wit h i di o p at hi c r e c urr e nt p eri c ar diti s 
wit h I nt erl e u ki n -1 r e c e pt or a nt a g o ni st ( a n a ki nr a). I nt J C ar di ol. 2 0 1 2; 1 6 0: 6 6 -7 7.  
1 9. S c ar d a p a n e A, Br u c at o A, C hi ar elli F, Br e d a L. Effi c a c y of a n I nt erl e u ki n - 1b  r ec e pt or a nt a g o ni st ( a n a ki nr a) i n i di o p at hi c 
r e c urr e nt p eri c ar diti s. P e di atr C ar di ol. 2 0 1 3; 3 4: 1 9 8 9-1 9 9 1.  
2 0. L a z ar o s G, V a sil ei o u P, K o ut si a n a s C, A nt o n at o u K, St ef a n a di s C, P e ct a si d e s D, V a s sil o p o ul o s D. A n a ki nr a f or t h e 
m a n a g e m e nt  of  r e si st a nt  i di o p at hi c  r e c urr e nt  p eri c ar diti s.  I niti al  e x p eri e n c e  i n  1 0  a d ult  c a s e s.  A n n  R h e u m  Di s. 
2 0 1 4; 7 3: 2 2 1 5 -2 2 1 7.  

 
 
Pil ot st u dy of A n aki nr a  f or ac ut e p eric ar ditis  
V ersi o n 2  
2 1.  Fi n etti  M,  I n s al a c o  A,  C a nt ari ni  L,  et  al .  L o n g-t er m  effi c a c y  of  I nt erl e u ki n-1  r e c e pt or  a nt a g o ni st  ( a n a k i nr a)  i n 
c orti c o st er oi d -d e p e n d e nt a n d c ol c hi ci n e -r e sist a nt r e c urr e nt p eri c ar diti s. J P e di atr. 2 0 1 4; 1 6 4: 1 4 2 5 -1 4 3 1.  
2 2.  J ai n  S,  T h o n g pr a y o o n  C,  E s pi n o s a  R E,  et  al .  Eff e cti v e n e s s  a n d  s af et y  of  a n a ki nr a  f or  m a n a g e m e nt  of  r efr a ct or y 
p eri c ar diti s. A m J C ar di ol. 2 0 1 5; 1 1 6: 1 2 7 7 -1 2 7 9.  
2 3. Br u c at o A, I m a zi o M, M a e str o n i S, et al . A n a ki nr a i n p ati e nt s wit h c orti c o-d e p e n d e nt i di o p at hi c r e c urr e nt p eri c ar diti s: a 
r a n d o mi z e d d o u bl e-bli n d pl a c e b o -c o ntr oll e d wit h dr a w al tri al [ a b str a ct]. Art hriti s R h e u m at ol. 2 0 1 5; 6 7( s u p pl 1 0). A b str a ct 
n u m b er 3 0 7 7.  
2 4.  D’ Eli a  E,  Br u c at o  A,  P e dr otti  P,  et  al .  S u c c e s sf ul  tr e at m e nt  of  s u b a c ut e  c o n stri cti v e  p eri c ar diti s  wit h  i nt erl e u ki n- 1b  
r e c e pt or a nt a g o ni st. Cli n E x p R h e u m at ol. 2 0 1 5; 3 3: 2 9 4 -5.  
2 5. L a z ar o s G, V a sil ei o u P, D a ni a s P, et al . Eff u si v e-c o n stri cti v e p eri c ar diti s s u c c e s sf ull y tr e at e d wit h  a n a ki nr a. Cli n E x p 
R h e u m at ol. 2 0 1 5; 3 3: 9 4 5.  
2 6 . M a ur o A G, T h ur b er C J, A b b at e A. C ol c hi ci n e i n A c ut e M y o c ar di al I nf ar cti o n: “ T e a c hi n g N e w Tri c k s t o a n Ol d D o g”. 
Tr a n sl ati o n al M e di ci n e 2 0 1 5 ; Tr a n sl M e d 5: e 1 3 3.  
2 7 . V a n T a s s ell B W, T ol d o S, M e z z ar o m a E, A b b at e A. T ar g eti n g i nt erl e u ki n -1 i n h e art di s e a s e.  Cir c ul ati o n. 2 0 1 3; 1 2 8: 1 9 1 0 -
1 9 2 3.  
 
 

 
 
Pil ot st u dy of A n aki nr a  f or ac ut e p eric ar ditis  
V ersi o n 2  
 
 
S u bj e ct I d e ntifi er: 
D at e:  
 
Pl e a s e r at e t h e i nt e n sit y of y o ur p ai n b el o w: 
M ar k t h e ar e a s w h er e y o u c urr e ntl y f e el p ai n. 
 
 
Fr e q u e n c y of p ai n: 
_ _ _ C o n st a nt 
_ _ _ Fr e q u e nt 
_ _ _ I nfr e q u e nt 
_ _ _ U n k n o w n 
 
 
D e s cri pti o n of p ai n: 
_ _ _ A c hi n g 
_ _ _ B ur ni n g 
_ _ _ Cr a m pi n g 
_ _ _ Cr u s hi n g 
_ _ _ D ull  
_ _ _ N u m b n e s s  
_ _ _ Pi n s a n d n e e dl e s 
_ _ _ S h ar p 
_ _ _ S h o oti n g 
_ _ _ T hr o b bi n g 
 
 
C h a n g e i n p att er n of p ai n: 
H a s t h e p ai n c h a n g e d i n i nt e n sit y i n t h e l a st 2 4 h o ur s ? 
_ _ _ Y e s (if y e s, d e s cri b e b el o w) 
 
 
_ _ _ N o  
_ _ _ U n k n o w n 
C a u s e s of p ai n or w or s e ni n g of p ai n: 
_ _ _ M o v e m e nt  
_ _ _ C o u g hi n g  
_ _ _ C ol d  
_ _ _ H e at  
_ _ _ F ati g u e  
_ _ _ A n xi et y 
_ _ _ Ot h er ( d e s cri b e b el o w): 
 
 
W h at r eli e v e s t h e p ai n ? 
_ _ _ C ol d  
_ _ _ H e at  
_ _ _ E x er ci s e 
_ _ _ E ati n g 
_ _ _ M e di c ati o n s 
_ _ _ H er b al s 
_ _ _ A dj u v a nt s 
_ _ _ M a s s a g e 
_ _ _ R el a x ati o n  
_ _ _ R e st 
_ _ _ R e p o siti o ni n g 
_ _ _ Di str a cti o n 
 
 
R at e h o w t h e p ai n h a s h a d a n eff e ct i n e a c h ar e a i n t h e p a st 2 4 h o ur s: 
_ _ _ 0 or n o eff e ct 
_ _ _ 2 or mil d eff e ct 
_ _ _ 5 or m o d er at e eff e ct 
_ _ _ 1 0 s e v er e eff e ct 
 
I n t h e p a st 2 4 h o ur s, h o w m u c h h a v e t h e m e di c ati o n s or tr e at m e nt s e a s e d y o ur p ai n ? 
_ _ _ 0 or n o r eli ef 
_ _ _ 2 or mil d r eli ef 
_ _ _ 8 or r eli ef 
_ _ _ 1 0 or c o m pl et e r eli ef