Hasan Tahir

Secukinumab for long‐term treatment of psoriatic arthritis: 2‐year follow‐up from a phase 3, randomized, double‐blind, placebo‐controlled study

To assess the 2‐year efficacy and safety of the interleukin‐17A inhibitor, secukinumab, in active psoriatic arthritis (PsA).

Efficacy, safety, and tolerability of secukinumab in patients with active ankylosing spondylitis: a randomized, double-blind phase 3 study, MEASURE 3

BackgroundSecukinumab, an anti–interleukin-17A monoclonal antibody, improved the signs and symptoms of ankylosing spondylitis (AS) in two phase 3 studies (MEASURE 1 and MEASURE 2). Here, we present 52-week results from the MEASURE 3 study assessing the efficacy and safety of secukinumab 300 and 150 mg subcutaneous maintenance dosing, following an intravenous loading regimen.MethodsA total of 226 patients were randomized to intravenous secukinumab 10 mg/kg (baseline, weeks 2 and 4) followed by subcutaneous secukinumab 300 mg (IV-300 mg) or 150 mg (IV-150 mg) every 4 weeks, or matched placebo. Patients in the placebo group were re-randomized to subcutaneous secukinumab at a dose of 300 or 150 mg at week 16. The primary endpoint was the Assessment of SpondyloArthritis international Society criteria for 20% improvement (ASAS20) response rate at week 16 in the IV-300 mg or IV-150 mg versus placebo. Other endpoints assessed through week 52 included improvements in ASAS40, ASAS 5/6, Bath Ankylosing Spondylitis Disease Activity Index, and ASAS partial remission responses, as well as the change from baseline in high-sensitivity C-reactive protein levels. Statistical analyses followed a predefined hierarchical hypothesis testing strategy to adjust for multiplicity of testing, with non-responder imputation used for binary variables and mixed-model repeated measures for continuous variables.ResultsThe primary efficacy endpoint was met; the ASAS20 response rate was significantly greater at week 16 in the IV-300 mg (60.5%; P < 0.01) and IV-150 mg (58.1%; P < 0.05) groups versus placebo (36.8%). All secondary endpoints were met at week 16, except ASAS partial remission in the IV-150 mg group. Improvements achieved with secukinumab in all clinical endpoints at week 16 were also sustained at week 52. Infections, including candidiasis, were more common with secukinumab than with placebo during the placebo-controlled period. During the entire treatment period, pooled incidence rates of Candida infections and grade 3–4 neutropenia were 1.8% for both of these adverse events in secukinumab-treated patients.ConclusionsSecukinumab (300 mg and 150 mg dose groups) provided rapid, significant and sustained improvement through 52 weeks in the signs and symptoms of patients with AS. The safety profile was consistent with previous reports, with no new or unexpected findings.Trial registrationClinicalTrials.gov, NCT02008916. Registered on 8 December 2013. EUDRACT 2013-001090-24. Registered on 24 October 2013). The study was not retrospectively registered.

Secukinumab improves active psoriatic arthritis symptoms and inhibits radiographic progression: primary results from the randomised, double-blind, phase III FUTURE 5 study

Objectives To evaluate the effect of subcutaneous (s.c.) secukinumab, an interleukin-17A inhibitor, on clinical signs and symptoms and radiographic progression in patients with psoriatic arthritis (PsA). Methods Adults (n=996) with active PsA were randomised 2:2:2:3 to s.c. secukinumab 300 mg or 150 mg with loading dose (LD), 150 mg without LD or placebo. All groups received secukinumab or placebo at baseline, weeks 1, 2 and 3 and then every 4 weeks from week 4. The primary endpoint was the proportion of patients achieving an American College of Rheumatology 20 (ACR20) response at week 16. Results Significantly more patients achieved an ACR20 response at week 16 with secukinumab 300 mg with LD (62.6%), 150 mg with LD (55.5%) or 150 mg without LD (59.5%) than placebo (27.4%) (p<0.0001 for all; non-responder imputation). Radiographic progression, as measured by van der Heijde-modified total Sharp score, was significantly inhibited at week 24 in all secukinumab arms versus placebo (p<0.01 for 300 mg with LD and 150 mg without LD and p<0.05 for 150 mg with LD; linear extrapolation). Adverse event rates at week 24 were similar across treatment arms: 63.1% (300 mg with LD), 62.7% (150 mg with LD), 61.1% (150 mg without LD) and 62.0% (placebo). No deaths or new safety signals were reported. Conclusion S.c. secukinumab 300 mg and 150 mg with and without LD significantly improved clinical signs and symptoms and inhibited radiographic structural progression versus placebo at week 24 in patients with PsA. Trial registration number NCT02404350; Results.

Secukinumab in the treatment of psoriatic arthritis: efficacy and safety results through 3 years from the year 1 extension of the randomised phase III FUTURE 1 trial.

Objective To assess the long-term (3 year) efficacy and safety of secukinumab in patients with active psoriatic arthritis (PsA) in the extension phase of the FUTURE 1 study (NCT01892436). Methods Following the 2-year core trial, eligible patients receiving subcutaneous secukinumab 150 or 75 mg entered a 3-year extension phase. Results are presented for key efficacy and safety endpoints at week 156. Results In total, 460 patients entered the extension study; 308 patients originally randomised to secukinumab were assessed for efficacy. Sustained improvements in all efficacy endpoints were achieved with secukinumab through week 156. Overall, 76.8%/54.9% (secukinumab 150 mg) and 65.2%/39.0% (secukinumab 75 mg) of patients achieved an American College of Rheumatology (ACR) 20/50 response (multiple imputation data); ACR20 responses were sustained irrespective of previous anti-tumour necrosis factor exposure. Improvements in quality of life and physical function were also sustained through week 156. Radiographic results (observed data; van der Heijde modified total Sharp score (mTSS)) showed that 78.1% (secukinumab 150 mg) and 74.8% (secukinumab 75 mg) of patients had no radiographic progression (≤0.5 increase in mTSS) through week 156. Exposure-adjusted incidence rates for selected adverse events per 100 patient-years (secukinumab 150/75 mg) were serious infections (1.7/1.6), Candida infections (1.4/0.7), Crohn’s disease (0/0.3), ulcerative colitis (0/0.3) and major adverse cardiac events (0.3/0.8). Conclusion Subcutaneous secukinumab provided sustained improvements in the signs and symptoms, quality of life and physical function of patients with active PsA with low rate of radiographic disease progression through 3 years. Secukinumab was well tolerated with no new safety signals.

Severe gangrene in a patient with anti-RNP positive limited cutaneous systemic sclerosis/rheumatoid arthritis overlap syndrome caused by vasculopathy and vasculitis

In this paper, we describe a case of a male patient with anti-U1RNP positive limited cutaneous systemic sclerosis/rheumatoid arthritis overlap syndrome, who presented acutely with rapidly progressive digital ischemia, which lead to extensive gangrene. Management with conventional vasodilator therapy was unsuccessful. There were constitutional symptoms and a marked inflammatory response in the absence of evidence of infection, implying a component of vasculitis underlying the presentation. Treatment with immunosuppression and intravenous immunoglobulin led to resolution of the inflammatory process with no further progression of tissue necrosis. Here we discuss pertinent issues raised by the case, including the management of digital ischemia and gangrene in this context and the relevance of the anti-U1RNP in systemic sclerosis overlap syndromes.

A pilot study investigating whether quantitative sensory testing alters after treatment in patients with fibromyalgia

Background: Fibromyalgia is a chronic musculoskeletal pain condition that is often associated with sleep disturbances and fatigue. The pathophysiology of fibromyalgia is not understood, but indirect evidence suggests a central dysfunction of the nociceptive modulating system. The aim of this study was to evaluate whether quantitative sensory testing detects a change in pain thresholds in fibromyalgia patient receiving pregabalin treatment. Methods: A total of 25 patients were recruited for the study and received routine pregabalin, but only 14 patients completed the treatment. Assessment of pressure pain thresholds and changes in conditioned pain modulation using ischaemic pain as a conditioning stimulus were measured at baseline and every 4 weeks for 12 weeks. Fibromyalgia impact questionnaire, PainDETECT and SF-12 were also completed. Results: Patients with fibromyalgia demonstrated a less-efficient conditioned pain modulation at baseline. An efficient conditioned pain modulation was observed at 1 month and this was maintained until the final visit. Pressure pain thresholds (PPTs) showed a significant improvement from baseline. Patients also reported a similar magnitude of improvements in PainDETECT, fibromyalgia impact questionnaire (FIQ) and its impact on daily life and change in outcome for SF-12. Conclusion: This pilot study reports an increase in PPTs and improved conditioned pain modulation response after commencing pregabalin, which was maintained at 12 weeks, and this was supported by positive pain scores. Pregabalin is a licenced treatment for fibromyalgia in Europe, and its response to central sensitisation, particularly ‘dynamic responses’, has not been reported. We conclude that pregabalin has the potential to reduce peripheral and central sensitisation in patients with fibromyalgia, as measured using quantitative sensory testing.

Teriparatide and vertebral fracture healing in Ankylosing Spondylitis

Summary Patients with Ankylosing Spondylitis (AS) are four times more likely to sustain spinal fractures. Due to the associated risk of neurological complications treatment is complex. We present the case of a 56-year-old Caucasian gentleman with AS who sustained a fracture of T2 vertebra following a traumatic hyperextension injury. He declined surgery in fear of complications and started treatment with subcutaneous Teriparatide at a dose of 20 mg daily for six months. There was complete healing of the vertebral fracture at 6 months without any complications. This case is unique as complete healing was achieved without preceding surgical intervention. Further exploration of the use of Teriparatide in spinal fractures in patients with AS is recommended to support the theories generated by this and other existing cases in the literature.

10. Reactivation of hepatitis B virus in a patient with psoriatic arthritis treated with methotrexate

Introduction: Transaminitis in psoriatic arthritis treated with disease modifying anti-rheumatic drugs (DMARDs) is common and significant liver damage is three times Health NHS more likely than in rheumatoid arthritis. Commonly described risk factors include non-alcoholic fatty liver disease,obesity, diabetes,alcohol, concomitant non-steroidal antiinflammatory drugs, corticosteroids and other DMARDs. Reactivation of hepatitis B virus (HBV) in patients undergoing immunosuppressive therapy is a well-recognized and potentially fatal complication, yet preventable. Here we report a rare case of HBV reactivation in a patient with psoriatic arthritis shortly after starting methotrexate treatment and to emphasize the importance of baseline screening for chronic HBV infection. Case description: A 30-year old Caucasian male patient was referred with longstanding psoriatic arthritis in May 2017. He had been treated with sulfasalazine in the past but has been without immunosuppression due to family planning since 2011. On examination he had active skin psoriasis and polyarthritis. There was no other significant past medical history,hewasanon-smoker,consumedalcoholsocially anddidnotuse any illicit drugs. He had a long-term female sexual partner. His baseline blood tests including liver function tests were unremarkable. He was started on methotrexate 10 mg once weekly and folic acid 5 mg once weekly. On his two-week monitoring blood test his liver function tests were markedly deranged including alanine aminotransferase (ALT) of 2577 U/Landbilirubin67umol/L.Hedevelopedatransientperiodof jaundice lastedforoneweekbutdidnotseekmedicalattentionandcontinued with themethotrexate. Heattended his follow-up rheumatologyappointment four weeks after starting the methotrexate when he was no longer jaundiced and liver function test revealed improvement in his ALT at 119 U/L. Further liver investigations including a viral hepatitis screen revealed reactivation of HBV. His serology showed positive HBV surface antigen (HBsAg), low titre IgM core antibody, high titre IgG core antibody (anti-HBc), negative e antigen and positive e antibody, with an HBV DNA viral loadof2.11logIU/ml. Discussion: There is a vast amount of evidence that HBV-induced liver inflammation is in fact mainly immune-mediated. HBV replication and expression of viral epitopes in infected hepatocytes is followed by a predominantlyCD8þT-lymphocyteinducedacuteorchronicliver inflammation. In chronic HBV infection, spontaneous intermittent rises in ALT levels preceded by increase in serum HBV DNA are common. Immunosuppressivedrugscantriggertheseflares,andinparticularcorticosteroids can directly stimulate HBV replication. Furthermore, the immunosuppressiveeffectonthehost immunesystemindirectly leads to abundantviral replication. Inaddition,suddenwithdrawalof immunosuppressive drugscan result inanexaggeratedhost immune response leading to potentially life-threatening liver injury. The list of immunosuppressive drugs associated with HBV reactivation has been constantly expanding. The most commonly reported synthetic DMARD associatedwithHBVreactivation ismethotrexate.The riskofHBVreactivationbymethotrexate alone is thereforeconsidered tobe low buthigher with concomitant use of corticosteroids. Young male patients appear to be at highest risk of reactivation, although the risk mostly depends on HBsAgstatus.HBVscreeningstandardsandthepreventionofHBVreactivation have dramatically changed in thepastdecade. Improved recommendations regarding screening for HBV infection prior to starting immunosuppressive agents or chemotherapy have been mastered by variousgastroenterologysocieties. The latest one, forexample, the2017 clinical practice guideline by the European Association for the Study of i10 11–12 October 2017 POSTER CASE REPORTS

216. BARICITINIB, METHOTREXATE, OR BARICITINIB PLUS METHOTREXATE IN PATIENTS WITH MODERATELY-TO-SEVERELY ACTIVE RHEUMATOID ARTHRITIS WHO HAD RECEIVED LIMITED OR NO TREATMENT WITH DMARDS: EFFICACY AND SAFETY RESULTS FROM THE 52-WEEK PHASE 3 RA-BEGIN STUDY

Background: Baricitinib, an oral JAK1/JAK2 inhibitor, improves disease activity with an acceptable safety profile in patients with active rheumatoid arthritis (RA). We report efficacy and safety data for baricitinib as monotherapy or in combination with methotrexate (MTX), compared with MTX, in[for full text, please go to the a.m. URL]

Randomised, prospective, non-blinded pilot study comparing the effect of intramuscular steroid injections and intralesional steroid injections in the management of tennis elbow

Background Tennis elbow is an overuse injury affecting people performing repetitive forearm movements. It is a soft tissue disorder that causes significant disability and pain. The aim of the study was to establish that an intramuscular steroid injection is effective in the short-term pain relief and functional improvement of tennis elbow. The severity of pain at the injection site was monitored to determine whether the intramuscular injection is better tolerated than the intralesional injection. Methods and results 19 patients, who had no treatment for tennis elbow in the preceding 3 months, were recruited from Whipps Cross University Hospital, London, and were randomised to receive either 80 mg of intramuscular Depo-Medrone or 40 mg of intralesional Depo-Medrone injection. Blinding proved difficult as the injection sites differed and placebo arms were not included in the study. A Patient-Rated Tennis Elbow Evaluation (PRTEE) Questionnaire and a 10-point Likert scale were used to assess primary outcome. Six weeks after the treatment, there was a reduction in pain, improvement in function and total PRTEE scores in both intramuscular and intralesional groups (p=0.008) using a 95% CI for mean treatment difference of −26 to +16 points. A statistically significant result (p=0.001) in favour of intramuscular causing less pain at the injection site was noted. Conclusion Non-inferiority of intramuscular to intralesional injections was not confirmed; however, the intramuscular injection proved to be effective in reducing tennis elbow-related symptoms and was found less painful at the site of injection at the time of administration. Trial registration number EUDRACT Number: 2010-022131-11. REC Number: 10/H0718/76 (NRES, Central London REC 1).