Akihiko Asahina

Oral tofacitinib efficacy, safety and tolerability in Japanese patients with moderate to severe plaque psoriasis and psoriatic arthritis: A randomized, double-blind, phase 3 study.

Tofacitinib is an oral Janus kinase inhibitor that is being investigated for psoriasis and psoriatic arthritis. Japanese patients aged 20 years or more with moderate to severe plaque psoriasis and/or psoriatic arthritis were double‐blindly randomized 1:1 to tofacitinib 5 or 10 mg b.i.d. for 16 weeks, open‐label 10 mg b.i.d. for 4 weeks, then variable 5 or 10 mg b.i.d. to Week 52. Primary end‐points at Week 16 were the proportion of patients achieving at least a 75% reduction in Psoriasis Area and Severity Index (PASI75) and Physicians Global Assessment of “clear” or “almost clear” (PGA response) for psoriasis, and 20% or more improvement in American College of Rheumatology criteria (ACR20) for patients with psoriatic arthritis. Safety was assessed throughout. Eighty‐seven patients met eligibility criteria for moderate to severe plaque psoriasis (5 mg b.i.d., n = 43; 10 mg b.i.d., n = 44), 12 met eligibility criteria for psoriatic arthritis (5 mg b.i.d., n = 4; 10 mg b.i.d., n = 8) including five who met both criteria (10 mg b.i.d.). At Week 16, 62.8% and 72.7% of patients achieved PASI75 with tofacitinib 5 and 10 mg b.i.d., respectively; 67.4% and 68.2% achieved PGA responses; all patients with psoriatic arthritis achieved ACR20. Responses were maintained through Week 52. Adverse events occurred in 83% of patients through Week 52, including four (4.3%) serious adverse events and three (3.2%) serious infections (all herpes zoster). No malignancies, cardiovascular events or deaths occurred. Tofacitinib (both doses) demonstrated efficacy in patients with moderate to severe plaque psoriasis and/or psoriatic arthritis through 52 weeks; safety findings were generally consistent with prior studies.

Safety and efficacy of adalimumab treatment in Japanese patients with psoriasis: Results of SALSA study.

The safety and efficacy of adalimumab were evaluated over 24 weeks in Japanese patients with psoriasis in routine clinical practice. In this multicenter, observational, open‐label, postmarketing study, primary efficacy measures included the Psoriasis Area and Severity Index (PASI) and the Dermatology Life Quality Index (DLQI) in all patients with psoriasis. In patients with psoriatic arthritis (PsA), the 28‐joint Disease Activity Score (DAS28) and the visual analog scale (VAS) pain were also evaluated. Safety was assessed based on the frequency of adverse drug reactions (ADR). Among patients with psoriasis evaluated for efficacy (n = 604), significant improvements from baseline were observed in mean PASI and DLQI scores at weeks 16 and 24 (all P < 0.0001). Furthermore, in psoriasis patients without PsA, the PASI 75/90 response rates were 55.9%/28.4% at week 16 (n = 306) and 65.6%/43.3% at week 24 (n = 270), respectively. In patients with PsA evaluable for effectiveness, significant improvements from baseline were observed in PASI, DAS28 erythrocyte sedimentation rate, DAS28 C‐reactive protein and VAS pain at weeks 16 and 24 (all P < 0.0001). ADR and serious ADR were reported by 26.1% and 3.3%, respectively, of 731 safety evaluable patients with psoriasis; no unexpected safety findings were noted. The safety profile and effectiveness of adalimumab for the treatment of psoriasis in a routine clinical setting were as expected in Japanese patients.

Serum C-reactive protein levels in Japanese patients with psoriasis and psoriatic arthritis: Long-term differential effects of biologics.

Psoriasis has been shown to accompany systemic inflammation. We aimed to examine serum C‐reactive protein (CRP) levels in Japanese psoriatic patients, and to elucidate their long‐term as well as short‐term changes by treatment with different biologics. A retrospective study was conducted in those who initiated and successfully continued the treatment for up to 24 months with either infliximab, adalimumab or ustekinumab, at the psoriasis special clinic of Jikei University School of Medicine. A total of 212 patients were included, 171 with plaque‐type psoriasis (PsV) and 41 with psoriatic arthritis (PsA). A statistically significant elevation of CRP values was found in the group with a Psoriasis Area and Severity Index (PASI) of 12 or more compared with the PASI of less than 12 for both PsV and PsA. The CRP‐positive patients had a higher proportion of PsA compared with the CRP‐negative patients, and they had significantly higher PASI scores. Serum CRP values declined as early as at 3 months after systemic treatment with biologics. Tumor necrosis factor (TNF)‐α antagonists did lead to a notable and sustained CRP decline up to 24 months. Infliximab showed rapid decline, while CRP decline by adalimumab treatment was time‐dependent. The interleukin‐12/23 p40 antagonist, ustekinumab, appeared to be less potent than TNF‐α antagonists in stabilizing CRP values at low levels despite good control of cutaneous lesions. In conclusion, serum CRP levels can be used to assess disease severity in Japanese psoriatic patients as a marker of systemic inflammation. TNF‐α antagonists may be more beneficial than ustekinumab in this regard.

Adalimumab treatment optimization for psoriasis: Results of a long-term phase 2/3 Japanese study

The tumor necrosis factor‐α inhibitor, adalimumab, is approved to treat moderate‐to‐severe plaque psoriasis (40 mg every‐other‐week or 80 mg every‐other‐week following inadequate response at 40 mg in Japan). This open‐label extension (OLE) trial evaluated the optimal adalimumab dose for long‐term efficacy and safety in Japanese patients with moderate‐to‐severe plaque psoriasis following a prior 24‐week, phase 2/3, randomized, double‐blind study. Of the 169 patients from the phase 2/3 trial, 147 entered the OLE on 40 mg (n = 89) or 80 mg (n = 58) adalimumab every‐other‐week. Patients on 40 mg with Psoriasis Area and Severity Index (PASI) of less than 50 could escalate to 80 mg. At week 52 (28 of OLE), patients entering the OLE on 80 mg were reduced to 40 mg, with the option to re‐escalate. For patients entering the OLE on 40 mg, final PASI 50/75/90 response rates were 85.1%/73.3%/60.4%, respectively, including effects of dose escalation. Among patients whose dose was escalated, final PASI 50/75/90 response rates were 70.0%/53.3%/36.7%, respectively. For patients entering the OLE on 80 mg, final PASI 50/75/90 response rates were 92.5%/84.9%/73.6%, respectively, including effects of dose re‐escalation. Overall incidence rates of adverse events (AE) and injection‐site reaction AE declined over time; rates for serious AE and infections were generally stable. Clinically meaningful efficacy of adalimumab was sustained to 4 years. Dose escalation to 80 mg every‐other‐week for patients with suboptimal response to 40 mg every‐other‐week, and dose reduction to 40 mg every‐other‐week for patients satisfactorily controlled on 80 mg every‐other‐week, are viable strategies for adalimumab optimization.

Biologic treatments for elderly patients with psoriasis

The number of elderly patients with psoriasis is increasing in Japan. However, biologic treatment is generally considered to be challenging in elderly patients, due to their increased risk of complications compared with younger patients. Our retrospective study aimed to evaluate the safety profile and efficacy of biologics in senior elderly patients (≥75 years old) with psoriasis. The study involved a cohort of 27 patients aged 75–88 years who were being treated with biologics over a period of more than 1 year. Initial biologics administrated to were adalimumab (five cases) and ustekinumab (22 cases). Eight patients discontinued treatment: two developed cancer; one was transferred to hospital; and five others experienced either bone fracture, interstitial pneumonia, cerebral hemorrhage resulting in death, decrepitude or developed hepatopathy following prophylactic tuberculosis treatment. Efficacy, evaluated by the percentage of patients achieving 75% reduction of Psoriasis Area and Severity Index score, was 76.9% at week 16 (n = 26), 88.0% at week 24 (n = 25) and 90.5% at week 52 (n = 21). Biologic treatments thus show clear efficacy in elderly patients with psoriasis, however, the increased frequency of adverse events requires rigorous patient observation.

Switching of biologics in psoriasis: Reasons and results.

Efficacy and safety profiles of biologics have been established for moderate to severe psoriasis. However, inefficacy or adverse events sometimes require changing the treatment to other biologics. Here, we examine the effectiveness of this strategy. We retrospectively investigated cases requiring switching biologics. We enrolled 275 psoriatic patients treated with biologics between January 2010 and December 2014 in our hospital. Of these, 51 required a switch to another biologic. First‐line therapies were infliximab (IFX, n = 26), adalimumab (ADA, n = 18) and ustekinumab (UST, n = 7), and second‐line therapies were IFX (n = 5), ADA (n = 21) and UST (n = 25). Reasons for switching were inefficacy (n = 38), adverse events (n = 11) and others (n = 2). The details were primary failure (n = 15), secondary failure (n = 23) and infusion reactions (n = 8). In 49 patients who switched biologics due to inefficacy and adverse events, the mean Psoriasis Area and Severity Index (PASI) score at week 16 was 4.3 for first‐line therapies and 2.9 for second‐line therapies (P < 0.05). Switching to a second biologic therapy to address the firsts inefficacy or adverse events often results in significant improvement in moderate to severe psoriasis.

Impact of anti-tumor necrosis factor-α agents on serum levels of KL-6 and surfactant protein-D in patients with psoriasis

We longitudinally examined the influence of anti‐tumor necrosis factor (TNF)‐α treatment on serum levels of KL‐6 and surfactant protein‐D (SP‐D). The study group comprised 22 patients with psoriasis treated with infliximab or adalimumab and with no history of interstitial lung disease (ILD). KL‐6 and SP‐D levels were measured in serum samples. Twelve of the 22 patients (55%) showed at least a 20% increase in KL‐6 levels compared with baseline. Of these 12 patients, none exhibited any signs of ILD on chest computed tomography and nine who showed an increase in KL‐6 levels (75%) showed at least a 20% increase in SP‐D levels. Some patients showed simultaneous increases in KL‐6 and SP‐D levels after treatment with anti‐TNF‐α agents. Although these patients may have undetectable or subtle alveolar damage, careful observation is needed.

Interstitial pneumonia in two patients with psoriasis during ustekinumab treatment.

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Mycobacterium haemophilum infection with prominent facial manifestation mimicking leprosy.

Mycobacterium haemophilum is a slow‐growing non‐tuberculous mycobacterium that is rarely known to cause human skin infection, particularly in immunocompromised patients. We recently experienced a 69‐year‐old Japanese woman with this infection who had been under immunosuppressive treatment for recalcitrant rheumatoid arthritis. The patient showed disseminated erythematous plaques and subcutaneous nodules on the face and extremities, and interestingly, the face manifested with a striking “facies leontina” appearance. Biopsy revealed abscess and granulomatous dermatitis with the involvement of peripheral nerve bundles and the presence of innumerable acid‐fast bacilli, thus necessitating differentiation from lepromatous leprosy. M. haemophilum was identified by molecular characterization as well as by successful culture with iron supplements. Although drug susceptibility testing indicated responsiveness to multiple antibiotics administrated simultaneously for the treatment, it took over 6 months to achieve significant improvement, and we also employed concurrent oral potassium iodide administration and repeated surgical excision. This case highlights the importance of continuous combination therapy for successful outcome in this rare infection. Furthermore, application of potassium iodide for mycobacterial infection warrants further evaluation by accumulating more cases.

Dual energy CT iodine map for delineating inflammation of inflammatory arthritis

Iodine mapping is an image-processing technique used with dual-energy computed tomography (DECT) to improve iodine contrast resolution. CT, because of its high spatial resolution and thin slice reconstruction, is well suited to the evaluation of the peripheral joints. Recent developments in the treatment of inflammatory arthritis that require early diagnosis and precise therapeutic assessment encourage radiological evaluation. To facilitate such assessment, we describe DECT iodine mapping as a novel modality for evaluating rheumatoid arthritis and psoriatic arthritis of the hands and feet.Key Points• Dual-energy CT iodine mapping can delineate inflammation of peripheral inflammatory arthritis.• DECT iodine mapping has high spatial resolution compared with MRI.• DECT iodine mapping has a high iodine contrast resolution.• DECT iodine mapping may reflect therapeutic effects.