Psoriatic Arthritis (PsA)

Risk Signs for Psoriatic Arthritis

1. Skin Psoriasis (Ps)

2. Nail Psoriasis

3. Over-weight

4. Young age @ Onset of Ps

5. Family member with PsA

6. Strep Throat Infection

7. Joint Injury

8. HIV

https://www.youtube.com/watch?v=G0gsfc1nGC4

Clinical Review on Psoriatic Arthritis

Psoriatic arthritis (PsA) is a systemic musculoskeletal disease with a wide range of clinical presentations, including peripheral or axial arthritis, inflammation at sites where ligaments and tendons attach to bone, diffuse swelling of a finger or toe, or plaque psoriasis. Its severity ranges from mild to disabling. PsA is distinguished from other inflammatory arthritis by abnormal bone turnover, leading to osteoporosis and extensive resorption accompanied by new bone formation.

Five clinical subtypes of PsA have been identified, with some overlap: (1) spondyloarthritis, (2) arthritis mutilans, (3) predominant distal interphalangeal disease, (4) symmetric polyarthritis, and (5) asymmetric oligoarthritis.

Recommended first-line treatment of moderate-to-severe PsA consists of methotrexate (MTX) or biologic therapy, or a combination of both. A 2012 study failed to demonstrate any significant difference between MTX and placebo in PsA. However, MTX is still in widespread use, in part because of its low cost. Anti-tumor necrosis factor (TNF) agents such as etanercept, adalimumab, infliximab, golimumab, and certolizumab have been shown to safely reduce symptoms and inhibit the radiographic progression of joint space narrowing and bone erosion in PsA, and thus have become the Gold standard for treatment. However, up to 50% of patients with PsA are either intolerant of anti-TNF therapy or fail to achieve an adequate response, and the majority of patients who fail therapy with anti-TNF biologics do not respond to a switch in TNF agents.

Despite the need to manage symptoms and comorbidities and to improve quality of life (QoL), many patients with PsA are currently under-treated, untreated, or dissatisfied with the treatments they are provided.

In a recent survey, 31.3% of patients with psoriasis and 40.7% of patients with PsA indicated that primary goals of therapy were not met by their current treatment. Dissatisfaction with the long-term safety of biologic therapy was reported by 31.8% of patients with psoriasis and 25.2% of patients with PsA. Most survey participants (87.8% of patients, 98.0% of dermatologists, and 98.0% of rheumatologists) believed there was a strong or moderate need for better therapies. Among patients, 51.5% indicated that current therapies can be worse than the condition itself, compared with 30.7% of dermatologists and 12.0% of rheumatologists. In addition, 48.5% of dermatologists and 31.0% of rheumatologists reported that an important issue is patients leaving their practice because of frustration or dissatisfaction with currently available therapies.

Multiple IL-17–related genes have been shown by genome-wide association studies to be associated with PsA. IL-17A, IL-17C, and IL-17F levels are elevated in psoriatic skin lesions and can act directly on keratinocytes, inducing expression of other proinflammatory molecules. The IL-17 inhibitor secukinumab received FDA approval for the treatment of patients with active PsA in January 2016, after having received approval in 2015 for the treatment of patients with moderate-to-severe plaque psoriasis. Approval for the treatment of PsA was based on the FUTURE-1 and FUTURE-2 studies, both of which had a primary endpoint of a minimum 20% improvement in the American College of Rheumatology response criteria (ACR20) at 24 weeks. In both trials, ACR20 response rates were significantly higher in patients receiving secukinumab than in those receiving placebo.Analysis of all primary and secondary endpoints from the FUTURE-1 study, on an intent-to-treat basis, continued to Week 104. Secukinumab showed sustained efficacy across multiple domains of PsA through Week 104, including signs and symptoms, disease activity, QoL, physical function, skin symptoms, dactylitis, and enthesitis. At Week 104, 84.3% of patients in the secukinumab 150 mg group and 83.8% in the secukinumab 75 mg group showed no radiographic disease progression. Ixekizumab, an IL-17 monoclonal antibody, received FDA approval for moderate-to-severe plaque psoriasis in March 2016 and is in late-stage trials for PsA.

In the recently reported double-blind, phase III SPIRIT-P1 trial, biologic-naïve patients with active PsA who were randomized to ixekizumab treatment saw improvements in disease activity and physical function, as well as in the inhibition of structural damage progression. At Week 25, ACR20 response rates, which was the primary endpoint, were 57.9% for patients who received ixekizumab 80 mg every 4 weeks and 62.1% for patients who received ixekizumab 80 mg once every 2 weeks. Results from the extension phase of the trial showed that over 52 weeks, ixekizumab demonstrated clinically significant improvement in the signs and symptoms of PsA, including arthritis, dactylitis, enthesitis, and skin manifestations, across treatment groups. In a placebo-controlled, phase 2 study, brodalumab, an IL-17 receptor monoclonal antibody (140 or 280 mg every 2 weeks) was evaluated in patients with active PsA. The ACR20 responses were achieved by 37% and 39% of patients in the respective brodalumab groups at Week 12 compared with 18% for placebo.

Abatacept, a selective T-cell costimulation modulator, and tofacitinib, an oral Janus kinase inhibitor, were approved by the FDA in 2017 to treat PsA. In a phase 3 trial involving 424 patients with PsA (approximately 60% with prior exposure to a TNF inhibitor and 60% on concomitant methotrexate), 39.4% of patients given abatacept experienced at least 20% improvement in the ACR20, compared with 22.3% among placebo-treated controls.

Ustekinumab, a fully human anti-IL-12/23p40 monoclonal antibody, also has FDA-approval alone or in combination with methotrexate for the treatment of adult patients (18 years or older) with active psoriatic arthritis.21

Apremilast, a phosphodiesterase 4 (PDE4) inhibitor, was approved by the FDA on March 21, 2014 for the treatment of adult patients with active psoriatic arthritis.

Tofacitinib is FDA-approved for the treatment of adults with PsA who have had an inadequate response or intolerance to methotrexate or other disease-modifying antirheumatic drugs, based on the results of the OPAL Broaden and OPAL Beyond studies, which demonstrated significant improvement in ACR20 response compared to placebo.22

Summary

Psoriatic arthritis is a systemic musculoskeletal disease with a broad constellation of clinical presentations, ranging from mild to disabling, including peripheral or axial arthritis, inflammation, diffuse swelling, joint destruction, and plaque psoriasis. Psoriatic arthritis is distinguished from other inflammatory arthritis by abnormal bone turnover, leading to osteoporosis and extensive resorption accompanied by new bone formation.2 Recent drug approvals have provided physicians with enhanced therapeutic options to manage this disease.

Ace the Case:

A 44-year old man with a 20-year history of psoriasis presents with a 2-month history of a painful, swollen left finger and a swollen right second toe. The patient has a 20-year history of psoriasis and is not receiving any medications. O/E the left third interphalangeal joint is swollen and tender to palpation and movement. The right second toe has fusiform swelling and is tender to palpation, with impaired range of motion. The nails show yellowish-pink discoloration with pitting and onycholysis. Radiographs of the affected joints demonstrate enthesitis and marginal bone erosions, with pencil-in-cup deformities of the distal interphalangeal joints of the left middle and index fingers, as well as dactylitis of the second toe. Labs show a sedimentation rate of 38 mm/1st hr; negative rheumatoid factor and anti-CCP antibody.

What is the likely diagnosis?

(A) Lyme Disease

(B) Psoriatic Arthritis

(C) Osteoarthritis

(D) Acute Gout

Answer: B

Rationale: Psoriatic arthritis (PsA) can affect approximately 30% of patients with psoriasis and is characterized by enthesitis, dactylitis, tenosynovitis, asymmetric oligoarthritis, spondylitis, and arthritis of the distal interphalangeal joints. The nails may show characteristic pitting or onycholysis. Approximately 15% of patients who present with PsA have undiagnosed psoriasis.1 Joint pattern of involvement in patients with PsA not only can involve the distal interphalangeal joints, but also can include symmetric polyarthritis, asymmetric oligoarthritis, arthritis mutilans, and spondylitis. Erosive changes of PsA can be associated with the pencil-in-cup deformities of the distal interphalangeal joints of the thumb and middle fingers. 1

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QUESTION 1

Which of the following medications is an IL-17 inhibitor?

(A) Tofacitnib

(B) Abatacept

(C) Secukinumab

(D) Certolizumab

Q1 Answer: C.

Rationale: The IL-17 inhibitor secukinumab received FDA approval for the treatment of patients with active PsA in January 2016, after having received approval in 2015 for the treatment of patients with moderate-to-severe plaque psoriasis.23 Approval for the treatment of PsA was based on the FUTURE-1 and FUTURE-2 studies, both of which had a primary endpoint of a ARC20 at 24 weeks.14,15

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QUESTION 2

Which of the following best describes the principle mechanism of action for tofacitinib?

(A) VEGF inhibitor

(B) IL-17 monoclonal antibody

(C) Janus kinase inhibitor

(D) Anti-CD40 antibody

Q2 answer: C

Rationale: Tofacitinib, a Janus kinase inhibitor, is FDA-approved for the treatment of adults with PsA who have had an inadequate response or intolerance to methotrexate or other disease-modifying antirheumatic drugs, based on the results of the OPAL Broaden and OPAL Beyond studies, which demonstrated significant improvement in ACR20 response compared to placebo.22

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https://cme.healio.com/rheumatology/ace-the-case/20181101/ace-the-case-a-44-year-old-man-with-psoriasis-presents-with-a-2-month-history-of-a-painful-swollen-finger-and-a-swollen-toe/overview

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Is It Psoriatic Arthritis, Gout, or Something Else?https://www.everydayhealth.com/psoriatic-arthritis/living-with/psoriatic-arthritis-gout-something-else/