Withdrawal of immunosuppressant or biologic therapy for patients with quiescent Crohn's disease.

BACKGROUND: Crohn's disease (CD) is a chronic, relapsing and remitting disease of the gastrointestinal tract that can cause significant morbidity and disability. Current treatment guidelines recommend early intervention with immunosuppressant or biological therapy in high-risk patients with a severe disease phenotype at presentation. The feasibility of therapeutic de-escalation once remission is achieved is a commonly encountered question in clinical practice, driven by patient and clinician concerns regarding safety, adverse events, cost and national regulations. Withdrawal of immunosuppressant and biologic drugs in patients with quiescent CD may limit adverse events and reduce healthcare costs. Alternatively, stopping these drug therapies may result in negative outcomes such as disease relapse, drug desensitization, bowel damage and need for surgery. OBJECTIVES: To assess the feasibility and safety of discontinuing immunosuppressant or biologic drugs, administered alone or in combination, in patients with quiescent CD. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase and the Cochrane IBD Group Specialized Register from inception to 19 December 2017. We also searched the reference lists of potentially relevant manuscripts and conference proceedings to identify additional studies. SELECTION CRITERIA: Randomized controlled trials (RCTs) and prospective cohort studies that followed patients for a minimum duration of six months after drug discontinuation were considered for inclusion. The patient population of interest was adults (> 18 years) with CD (as defined by conventional clinical, endoscopic or histologic criteria) who had achieved remission while receiving immunosuppressant or biologic drugs administered alone or in combination. Patients then discontinued the drug regimen following a period of maintenance therapy of at least six months. The comparison was usual care (i.e. continuation of the drug regimen). DATA COLLECTION AND ANALYSIS: The primary outcome measure was the proportion of patients who relapsed following discontinuation of immunosuppressant or biologic drugs, administered alone or in combination. Secondary outcomes included: the proportion of patients who responded to the reintroduction of immunosuppressant or biologic drugs, given as monotherapy or combination therapy; the proportion of patients who required surgery following relapse; the proportion of patients who required hospitalization for CD following relapse; the proportion of patients who developed new CD-related complications (e.g. fistula, abscesses, strictures) following relapse; the proportion of patients with elevated biomarkers of inflammation (CRP, fecal calprotectin) in those who stop and those who continue therapy; the proportion of patients with anti-drug antibodies and low serum trough drug levels; time to relapse; and the proportion of patients with adverse events, serious adverse events and withdrawal due to adverse events. For dichotomous outcomes, we calculated the risk ratio (RR) and 95% confidence interval (95% CI). Data were analyzed on an intention-to-treat basis where patients with missing outcome data were assumed to have relapsed. The overall quality of the evidence supporting the primary and secondary outcomes was assessed using the GRADE criteria. MAIN RESULTS: A total of six RCTs (326 patients) evaluating therapeutic discontinuation in patients with quiescent CD were eligible for inclusion. In four RCTs azathioprine monotherapy was discontinued, and in two RCTs azathioprine was discontinued from a combination therapy regimen consisting of azathioprine with infliximab. No studies of biologic monotherapy withdrawal were eligible for inclusion. The majority of studies received unclear or low risk of bias ratings, with the exception of three open-label RCTs, which were rated as high risk of bias for blinding. Four RCTs (215 participants) compared discontinuation to continuation of azathioprine monotherapy, while two studies (125 participants) compared discontinuation of azathioprine from a combination regimen to continuation of combination therapy. Continuation of azathioprine monotherapy was shown to be superior to withdrawal for risk of clinical relapse. Thirty-two per cent (36/111) of azathioprine withdrawal participants relapsed compared to 14% (14/104) of participants who continued with azathioprine therapy (RR 0.42, 95% CI 0.24 to 0.72, GRADE low quality evidence). However, it is uncertain if there are any between-group differences in new CD-related complications (RR 0.34, 95% CI 0.06 to 2.08, GRADE low quality evidence), adverse events (RR 0.88, 95% CI 0.67 to 1.17, GRADE low quality evidence), serious adverse events (RR 3.29, 95% CI 0.35 to 30.80, GRADE low quality evidence) or withdrawal due to adverse events (RR 2.59, 95% CI 0.35 to 19.04, GRADE low quality evidence). Common adverse events included infections, mild leukopenia, abdominal symptoms, arthralgias, headache and elevated liver enzymes. No differences between azathioprine withdrawal from combination therapy versus continuation of combination therapy were observed for clinical relapse. Among patients who continued combination therapy with azathioprine and infliximab, 48% (27/56) had a clinical relapse compared to 49% (27/55) of patients discontinued azathioprine but remained on infliximab (RR 1.02, 95% CI 0.68 to 1.52, P = 0.32; GRADE low quality evidence). The effects on adverse events (RR 1.11, 95% CI 0.44 to 2.81, GRADE low quality of evidence) or serious adverse events are uncertain (RR 1.00, 95% CI 0.21 to 4.66; GRADE very low quality of evidence). Common adverse events in the combination therapy studies included infections, liver test elevations, arthralgias and infusion reactions. AUTHORS' CONCLUSIONS: The effects of withdrawal of immunosuppressant therapy in people with quiescent Crohn's disease are uncertain. Low quality evidence suggests that continuing azathioprine monotherapy may be superior to withdrawal for avoiding clinical relapse, while very low quality evidence suggests that there may be no difference in clinical relapse rates between discontinuing azathioprine from a combination therapy regimen, compared to continuing combination therapy. It is unclear whether withdrawal of azathioprine, initially administered alone or in combination, impacts on the development of CD-related complications, adverse events, serious adverse events or withdrawal due to adverse events. Further high-quality research is needed in this area, particularly double-blind RCTs in which biologic therapy or an immunosuppressant other than azathioprine is withdrawn.

Investigation into the wait time for consultation in the psoriatic arthritis program.

The 2014 Update of the Canadian treatment recommendations for the management of spondyloarthritis recommended that patients at risk of peripheral spondyloarthritis, including patients with psoriatic arthritis (PsA), be assessed by a rheumatologist within 6 weeks of referral. This study aimed to: (1) investigate the proportion of PsA patients who were assessed by a rheumatologist within 6 weeks of referral to the PsA Clinic at Toronto Western Hospital and (2) investigate the possible reasons for delays for consult with a rheumatologist. We identified patients with PsA who were seen by rheumatologists at the PsA Clinic between January 2013 and May 2019. We used retrospective chart reviews of medical records and referral letters to determine the number of days between referral and assessment by a rheumatologist. The causes for delays were identified as no spots in the clinic or patient rescheduling their appointment due to their inability to attend the scheduled appointment. Among 168 patients, 43 (25.6%) patients met the recommendation. The median wait time was 78.5 days (IQR 83.5). The most common cause of delay was the lack of available spots in the PsA clinic. The majority of PsA patients at the TWH PsA Clinic were not seen within the wait-time recommendation. The most common factor that prevented a timely consultation with a rheumatologist was the lack of spots in the PsA clinic. Greater access to rheumatologists can improve the timely and effective care of PsA patients.

A case of recalcitrant silicone granuloma treated with adalimumab: A case report.

Liquid silicone is a relatively inexpensive injectable used for soft tissue augmentation. Injection of silicone is associated with a risk of delayed granuloma formation associated with elevated levels of tumour necrosis factor-α. We report a case of recalcitrant silicone granulomas following facial injections of silicone successfully treated with tumour necrosis factor-α blockade. Our case, as well as previous reports, demonstrates the effectiveness of this therapy for the treatment of foreign body granulomas from due to silicone.

Exploring cannabis use and perspectives among psoriatic disease patients.

OBJECTIVE: To assess the correlation between cannabis use and psoriatic disease severity, health-related quality of life, pain, psychosocial outcomes, and cytokine levels in psoriasis (PsC) and psoriatic arthritis (PsA) patients. METHODS: PsC and PsA patients enrolled in the International Psoriasis and Arthritis Research Team (IPART) program were surveyed on cannabis use and were asked to provide a serum and urine sample. Demographic and clinical variables were compared between users and non-users using Student's t-test or Mann-Whitney U test for continuous variables, and chi-square or Fisher's exact test for categorical variables. RESULTS: Of 151 respondents, 30% reported current cannabis use within the last year. Compared to non-users, cannabis users were younger and had a shorter PsA duration and poorer mental health as measured by the SF-36. Other measures of health-related quality of life and pain were comparable between the groups. Respondents' primary perceived benefits of cannabis use were aid in sleep and arthritis pain relief, but there was no difference in pain between users and non-users. No THC was detected in the urine of non-users while users had a mean level of 19.6 ng/ml. Serum IL-23 levels were statistically significantly higher in non-users than in users. CONCLUSION: A third of the patients used cannabis within the past year, and 54.3% of users reported the use of cannabis for arthritis pain relief. However, there was no difference in pain scores. Comprehensive education for providers on the current body of evidence and further studies on cannabis use and outcomes in psoriatic disease are needed. Key Points • A third of patients with psoriatic arthritis have used cannabis in the past year. • Most used it for better sleep and control of pain. • There was no difference in pain scores between users and non-users. • IL-23 levels were significantly higher in non-users.

Incidence, prevalence, and predictors of inflammatory arthritis in patients with hidradenitis suppurativa: a systematic review and meta-analysis.

An increasing amount of evidence has emerged suggesting that hidradenitis suppurativa (HS) is associated with inflammatory arthritis. This study reviewed the incidence, prevalence, and predictors of inflammatory arthritis in patients with HS. A comprehensive literature search was conducted in CINAHL, Embase, and Medline from inception to February 14, 2020. Articles were included in the review if they provided data on disease epidemiology or predictors of adult or pediatric HS patients with comorbid inflammatory arthritis. There are no validated diagnostic criteria for HS, thus we considered patients as having HS if they had at least one diagnostic code in a hospital or claims database or a diagnosis of HS/inflammatory arthritis in a medical record. The same criteria were used to confirm presence of inflammatory arthritis. We identified an increased incidence of rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) in HS patients when compared with estimates in the general population. We identified a relatively high prevalence of RA, spondyloarthritis (SpA), and PsA in HS patients when compared with estimates in the general population. There was evidence to suggest that patients who are younger than 30, male, have severe HS, or are taking infliximab or adalimumab (which may also be confounded by HS disease severity) may be at greater risk for specific subtypes of inflammatory arthritis. However, further data are needed to confirm these associations. The increased incidence and prevalence of inflammatory arthritis within HS patients underscore the need for increased awareness and interdisciplinary partnership within rheumatology and dermatology.

Clinical and laboratory prognosticators of atrophic papulosis (Degos disease): a systematic review.

BACKGROUND: Degos disease is a rare vascular disorder with a cutaneous-limited form, benign atrophic papulosis (BAP), and a systemic variant, malignant atrophic papulosis (MAP). Despite the poor prognosis of MAP, no study has established features associated with systemic disease. OBJECTIVES: The aims of this systematic review were to: (1) summarize clinical features and treatments implemented for patients with MAP and BAP (2) identify clinical and laboratory factors associated with the development of MAP, compared to BAP. METHODS: We systematically searched MEDLINE and Embase from inception to April 2020. Demographic and clinical features of Degos patients were presented descriptively; multivariable logistic regression was performed to identify associations with MAP. RESULTS: We identified 99 case studies, comprising 105 patients. MAP (64%) had a 2.15 year median survival time from cutaneous onset, most often with gastrointestinal or central nervous system involvement. We found that elevations in either of erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) were associated with systemic involvement (OR 2.27, p = 0.023). Degos secondary to an autoimmune connective tissue disease was found to be inversely associated with MAP (OR 0.08, p = 0.048). CONCLUSIONS: Elevated ESR or CRP is associated with MAP and may be a predictor of systemic involvement for patients with Degos disease. In addition, secondary Degos disease is associated with a favourable prognosis. Clinicians should be aware of the differences between primary and secondary Degos and the utility of ESR or CRP in identifying disease evolution to systemic involvement. The utility of ESR and CRP to identify systemic involvement should be further explored.

Premature Cardiac Disease and Death in Women Whose Infant Was Preterm and Small for Gestational Age: A Retrospective Cohort Study.

Importance: Women with an infant with preterm birth (PTB) or who was severely small for gestational age (SGA) are at higher future risk of premature cardiovascular disease and related death. Objective: To determine the risk of cardiac disease or death among women with an infant with both PTB and SGA. Design, Setting, and Participants: This population-based cohort study used electronic health records from the province of Ontario, Canada, where health care is universally available, between April 1, 2002, and March 31, 2016. All singleton live births between 23 to 42 weeks' gestation among 710 501 nulliparous women aged 16 to 50 years without prepregnancy cardiac disease were analyzed. Main Outcomes and Measures: Risk of a composite outcome of heart failure, atrial or ventricular dysrhythmia, or all-cause mortality, starting 30 days after the index birth. Hazard ratios were adjusted for maternal age, income quintile, and preeclampsia/eclampsia (each at the index birth), as well as diabetes, chronic hypertension, obesity, dyslipidemia, drug dependence or smoking, and kidney disease (each within 24 months before the index birth date and time-varying from the birth date onward). Results: Of 710 501 singleton live births, 15 082 mothers (2.1%) were older than age 40 years. Relative to having an infant without PTB or severe SGA (4.1 per 10 000 person-years), the incidence rate of the composite outcome of heart failure, dysrhythmia, or death was 11.3 per 10 000 person-years among mothers with an infant with PTB-SGA (crude hazard ratio, 2.79; 95% CI, 1.85-4.21) (adjusted hazard ratio, 1.66; 95% CI, 1.09-2.52). Conclusions and Relevance: Women who had an infant with PTB-SGA may be at higher future risk of premature cardiac disease or death.