Role of the IL-23/IL-17 Axis in Psoriasis and Psoriatic Arthritis: The Clinical Importance of Its Divergence in Skin and Joints.

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Annotation Summary

Term Occurence Count Dictionary
fibromyalgia 1 rheumatologydiseases
osteoarthritis 1 rheumatologydiseases
synovitis 1 rheumatologydiseases
sacroiliitis 1 rheumatologydiseases
Secukinumab 3 rheumatologydiseasesdrugs
adalimumab 3 rheumatologydiseasesdrugs
arthritis 13 rheumatologydiseases
methotrexate 3 rheumatologydiseasesdrugs
Etanercept 4 rheumatologydiseasesdrugs
Ustekinumab 5 rheumatologydiseasesdrugs
autoimmune disease 3 rheumatologydiseases
spondyloarthropathy 1 rheumatologydiseases
tofacitinib 2 rheumatologydiseasesdrugs
arthropathy 1 rheumatologydiseases
psoriatic arthritis 2 rheumatologydiseases
rheumatoid arthritis 1 rheumatologydiseases
spondylitis 2 rheumatologydiseases

Graph of close proximity drug and disease terms (within 200 characters).

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Select Drug Character Offset Drug Term Instance
Etanercept 40722 superiority of the anti-IL-23 p19 blockade by tildrakizumab over both placebo (reSURFACE-1, NCT01722331) and Etanercept (reSURFACE-2, NCT01729754) [[116]].Two molecules targeting IL-17 are currently in use: secukinumab and
Etanercept 53493 Briakinumab; MTX: Methotrexate; Gus: Guselkumab; Ada: Adalimumab; Ris: Risankizumab; Til: Tildrakizumab; Eta: Etanercept ; Sec: Secukinumab; Ixe: Ixekizumab; Bro: Brodalumab; PASI: Psoriasis Area and Severity Index; ACR: American
Etanercept 54665 20.2%Briakinumab (ABT-874, Ozespa)NCT00691964[[104]]PsoriasisIIIBri 200 mg × 2 then 100 mg (n = 138) Etanercept 50 mg twice-weekly (n = 141)Placebo (n = 68)Bri 81.9%Eta 56.0%Placebo 7.4%-NCT00679731[[105]]PsoriasisIIIBri
Etanercept 54947 163)(At week 24)Bri 81.8%MTX 39.9%-NCT00710580[[131]]PsoriasisIIIBri 200 mg × 2 then 100 mg (n = 138) Etanercept 50 mg twice-weekly (n = 141)Placebo (n = 68)Bri 80.6%Eta 39.6%Placebo 6.9%-NCT00570986[[106]]PsoriasisIIIBri
Secukinumab 40847 NCT01729754) [[116]].Two molecules targeting IL-17 are currently in use: secukinumab and ixekizumab. Secukinumab (Novartis Pharma AG, Basel, Switzerland) is a recombinant, high-affinity, fully human monoclonal anti-IL-17A
Secukinumab 53510 Methotrexate; Gus: Guselkumab; Ada: Adalimumab; Ris: Risankizumab; Til: Tildrakizumab; Eta: Etanercept; Sec: Secukinumab ; Ixe: Ixekizumab; Bro: Brodalumab; PASI: Psoriasis Area and Severity Index; ACR: American College of
Secukinumab 56401 200 mg (n = 314)Placebo (n = 156)Eta (n = 313)Til 100 mg 61%Til 200 mg 66%Placebo 6%Eta 48%-Anti-IL17A Secukinumab (AIN457, Cosentyx)ERASURENCT01365455[[118]]PsoriasisIIISec 150 mg (n = 245)Sec 300 mg (n = 245)Placebo
Ustekinumab 33588 targeting the p40 subunit, two molecules have been tested and approved: ustekinumab and briakinumab. Ustekinumab (CNTO 1275, Centocor Inc., Malvern, PA, USA) is a fully human monoclonal anti-IL12/23p40 antibody. Promising
Ustekinumab 34731 ustekinumab 45 and 90 mg, respectively), and still more than 50% reaching a PASI90 response [[94]]. Ustekinumab treatment was also beneficial in significantly improving nail psoriasis manifestations [[97]].In keeping
Ustekinumab 53365 1Randomized clinical trials on inhibitors of the IL-23/IL-17 axis in Psoriasis and Psoriatic Arthritis. Ust: Ustekinumab ; Bri: Briakinumab; MTX: Methotrexate; Gus: Guselkumab; Ada: Adalimumab; Ris: Risankizumab; Til: Tildrakizumab;
Ustekinumab 53881 EndpointSkinPASI75 at Week 12Unless Otherwise Specified Joint-RelatedACR20Unless Otherwise SpecifiedAnti-IL12/23p40 Ustekinumab (CNTO 1275, Stelara)PHOENIX 1NCT00267969[[92]]PsoriasisIIIUst 45 mg (n = 255)Ust 90 mg (n = 256)Placebo
Ustekinumab 58240 86%Ust 70%Placebo 8%-AMAGINE-3NCT01708629[[132]]PsoriasisIIIBro 140 mg (n = 629)Bro 210 mg (n = 624) Ustekinumab 45 mg (n = 313)Placebo (n = 315)Bro 140 mg 69%Bro 210 mg 85%Ust 69%Placebo 6%-NCT01516957PsAIIBro 280
adalimumab 38998 III multicentre randomised double-blind studies, guselkumab treatment was compared with placebo and adalimumab . In both the trials, >85% of the guselkumab-treated patients achieved PASI75 response (as compared with
adalimumab 39136 of the guselkumab-treated patients achieved PASI75 response (as compared with the PASI75 response to adalimumab ranging between 68.5% and 73.1%) [[110],[111]].Results from the NAVIGATE trial (NCT02203032) definitively
adalimumab 43662 achieving the ACR20 response at week 24 following treatment with ixekizumab in comparison with placebo and adalimumab . Ixekizumab was effective in reducing the activity and the radiologic progression of the joint disease,
methotrexate 9441 the other hand, the HLA-C*06 is strongly associated with Ps and predicts better clinical response to methotrexate (MTX) [[25]] and the IL-12/IL-23 antagonist ustekinumab [[26]] in psoriatic patients. Early data suggested
methotrexate 37521 trial (NCT00679731) included 317 patients with active Ps assigned to receive either briakinumab or methotrexate . The proportion of patients achieving PASI75 and PGA 0/1 at week 24 and 52 was significantly higher
methotrexate 37671 PASI75 and PGA 0/1 at week 24 and 52 was significantly higher in the briakinumab group compared to methotrexate , alongside with a greater number of serious adverse events [[105]]. Similar findings regarding not only
tofacitinib 49391 to target this pathway [[134]]. In pre-clinical studies involving synovial tissue from PsA patients, tofacitinib , a JAK1/3 inhibitor, has been shown to be able to down-regulate the secretion of pro-inflammatory cytokines,
tofacitinib 49679 to III clinical trials are investigating the role of JAK inhibitors in the treatment of Ps and PsA; tofacitinib , for instance, has been proved to be significantly more effective than placebo in PsA patients non-responders
Select Disease Character Offset Disease Term Instance
arthritis 2711 Arthritis (PsA) may develop; this is characterised by the presence of spondylitis, enthesitis or peripheral arthritis [[2]]. Despite being once considered as a relatively benign disease, it is now recognised that PsA is
arthritis 3746 include: (i) evidence of psoriasis; (ii) psoriatic nail dystrophy; (iii) negative tests for rheumatoid arthritis (RA); (iv) dactylitis; and (v) radiographic evidence of juxta-articular new bone formation [[7]]. Patients
arthritis 4520 reminiscent of the rheumatoid phenotype (polyarticular and symmetrical), however an asymmetrical mono/oligo arthritis is more commonly observed. The prevalent involvement of the distal interphalangeal joints is quite typical
arthritis 10176 response to treatment and for identifying psoriatic patients who are more likely to develop Ps-related arthritis [[30]]. For instance, an increase in urea cycle amino acids (e.g., arginine and citrulline) and in amino
arthritis 13057 macrophages (e.g., TNFα or IL-6) play a significant role in PsA too [[39]]. Compared to other inflammatory arthritis , the neutrophil component characterising the synovium in PsA is more abundant, mirroring the histological
arthritis 14425 http://www.peac-mrc.mds.qmul.ac.uk/) [[44]], a large multicentre observational study recruiting early arthritis , treatment-naïve patients affected by peripheral joint inflammation. The detailed assessment of the
arthritis 20269 and F. Of them, IL-17A is the principal effector of the IL-17-related inflammatory activity in Ps and arthritis . A similarly significant role is also played by IL-17F, which is closely related to IL-17A and like
arthritis 23943 IL-23/IL-17 pathway (IL17, IL22, IL23A) have been silenced are protected from both Ps and inflammatory arthritis , hence supporting the pathogenic role for the IL-23/IL-17 axis in these conditions [[62]]. Interestingly,
arthritis 30214 macrophages [[74]] and is particularly raised in synovial fluids of PsA patients in comparison with osteo arthritis controls. In vitro, IL-22 can induce the proliferation of FLS in synergy with TNFα [[87]]. Even if
arthritis 31864 notable improvement of the clinical outcome of patients affected by skin psoriasis and inflammatory arthritis like PsA and RA. The availability of targeted treatment in association with the recognised importance
arthritis 36657 been recommended since 2015 not only for skin and nail psoriasis but also for peripheral psoriatic arthritis in Disease Modifying Anti-Rheumatic Drugs (DMARDs) non-responders patients [[103]].Briakinumab (ABT-874,
arthritis 42506 been approved for the treatment of both moderate-to-severe plaque psoriasis and peripheral psoriatic arthritis in DMARDs-failure patients [[124]]. To note, in both FUTURE 1 and FUTURE 2, the percentage of patients
arthritis 50327 tested by Li and colleagues and showed to be effective to ameliorate the outcome of animal models of arthritis [[137]] while human studies are underway.Finally, over the last few years, novel critical antagonists
arthropathy 2573 skin epithelial cells. In up to 30% of patients with skin psoriasis, a chronic seronegative spondylo arthropathy defined Psoriatic Arthritis (PsA) may develop; this is characterised by the presence of spondylitis,
autoimmune disease 15397 antigen(s) responsible for triggering the autoimmune reaction has not been identified yet. As per other autoimmune disease s, it has been suggested that the breakdown of the immune tolerance to potential antigens of infective
autoimmune disease 18369 of Ectopic Lymphoid Structures (ELS). These lymphocytic structures, which can be found not only in autoimmune disease s but also in association with infections and cancer [[56]], have been shown to be able to self-sustain
autoimmune disease 32172 remission achievable goals. In keeping with the well-established role played by Th17 cells in numerous autoimmune disease s including psoriatic disorders, a considerable effort has been made over the last years into the development
fibromyalgia 11539 metabolic syndrome, Inflammatory Bowel Diseases (IBD) and osteoporosis, together with depression and fibromyalgia , play a major role. The prevalence of each of these manifestations may vary greatly between the two
osteoarthritis 30209 macrophages [[74]] and is particularly raised in synovial fluids of PsA patients in comparison with osteoarthritis controls. In vitro, IL-22 can induce the proliferation of FLS in synergy with TNFα [[87]]. Even if
psoriatic arthritis 36647 ustekinumab has been recommended since 2015 not only for skin and nail psoriasis but also for peripheral psoriatic arthritis in Disease Modifying Anti-Rheumatic Drugs (DMARDs) non-responders patients [[103]].Briakinumab (ABT-874,
psoriatic arthritis 42496 secukinumab has been approved for the treatment of both moderate-to-severe plaque psoriasis and peripheral psoriatic arthritis in DMARDs-failure patients [[124]]. To note, in both FUTURE 1 and FUTURE 2, the percentage of patients
rheumatoid arthritis 3735 group, which include: (i) evidence of psoriasis; (ii) psoriatic nail dystrophy; (iii) negative tests for rheumatoid arthritis (RA); (iv) dactylitis; and (v) radiographic evidence of juxta-articular new bone formation [[7]]. Patients
sacroiliitis 4899 Overall, around 50% of patients affected by PsA may show axial manifestations such as spondylitis and sacroiliitis [[11]]. Moreover, inflammation of the entheses (enthesitis) and dactylitis are frequently found in PsA
spondylitis 2673 spondyloarthropathy defined Psoriatic Arthritis (PsA) may develop; this is characterised by the presence of spondylitis , enthesitis or peripheral arthritis [[2]]. Despite being once considered as a relatively benign disease,
spondylitis 4883 mutilans [[10]]. Overall, around 50% of patients affected by PsA may show axial manifestations such as spondylitis and sacroiliitis [[11]]. Moreover, inflammation of the entheses (enthesitis) and dactylitis are frequently
spondyloarthropathy 2565 growth of skin epithelial cells. In up to 30% of patients with skin psoriasis, a chronic seronegative spondyloarthropathy defined Psoriatic Arthritis (PsA) may develop; this is characterised by the presence of spondylitis,
synovitis 12449 resembles the pattern observed in other spondyloarthropaties rather than the rheumatoid-associated synovitis [[39]]. A mild to moderate lining layer hyperplasia and tortuous blood vessels are predominant features,

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