CanVasc Journal Watch

Selected News and Articles

NOTE: Due to copyright policies, we can not directly provide here the full texts of the commented articles. Links will lead you to the Journal pages of the articles, where you will be able to get acces to them, through a single article purchase or through your own subscriber account or that of your institution. In case of major, vital and urgent need to get access to one of the articles, you still may try to contact us by email if you have no other options.

Health Canada approves avacopan for the treatment of severe MPA and GPA

Health Canada approved in mid-April 2022 avacopan as an "[...] adjunctive treatment of adult patients with severe active anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (granulomatosis with polyangiitis [GPA] and microscopic polyangiitis [MPA]) in combination with standard background therapy including glucocorticoids. [Avacopan] does not eliminate glucocorticoid use." Let's wait now for the CADTH review recommendations, which will also determine how this agent can be used (and covered, as it will likely be an expensive treatment option) in each Canadian province (CPx - 19 Apr 2022).

A new review article on maintenance treatments of AAV by two CanVasc core members

A new review article with free access to read on line (downladable only if you or your insitition have a subscription to the journal) on maintenance treatments in AAV. LINK HERE (CPx - 30 Apr 2021).

Pediatric Consensus Treatment plans for new-onset GPA, MPA and RLV

An excellent and original approach to better study and compare the best treatment options for children with AAV, from the CARRA group, led by Vancouver pediatricians, including CanVasc core members! LINK HERE

A new study on MRI in GCA from the Hamilton's group

Including some members of CanVasc. LINK HERE

The FDA and HC approved mepolizumab (300 mg SC monthly) for EGPA

The FDA approved on December 12th, 2017, then Health Canada on July 17th, 2018, the use of mepolizumab to treat adults with EGPA, based on the results of the MIRRA trial. Let's follow now on the coverage options in every province and with the drug insurance companies. - CPx 09 Feb 2019.

Link to the FDA news HERE and to the HC approval here.

The FDA approves rituximab for maintenance in GPA and MPA!

CanVasc tried to ask for the approval of rituximab for maintenance in GPA or MPA but it seemed that the Canadian institution(s) did not want to be the first on this.

Well... The FDA approved on October 19th, 2018, the use of rituximab for "follow-up" (meaning maintenance) in GPA or MPA, based on several cohort studies and, most importantly, the results of the MAINRITSAN trial. The results of the latter pivotal study were published 4 years ago and its raw data were re-checked, re-analyzed and surgically debrided, with the help of the study's main investigators, in order to be confirmed without any lingering doubt, and this all ended up with this very good news for our GPA and MPA patients. Let's follow on this now with the Canadian institutions, Health Canada then in every province and with the drug insurance companies. This may take a few months more, but our hopes to get it finally covered when indicated and justified are much higher now! - CPx 20 Oct 2018.

Link to the news HERE 

JAKinibs for GCA?

Whereas the light has been shed in the past months on tocilizumab (and abatacept) for GCA, not all patients achieve remission and/or remain in sustained remission with these agents and research efforts must continue to find other effective agents (as alternative or in combination). The recent research article from the Weyand's group highlights the potential place of JAKinibs (tofacitinib especially) for GCA, based on results obtained in a mouse model of GCA (chimeric mice, engrafted with a human large temporal artery fragment). Studies in humans are on the go, with baracitinib for the moment. CPx, 06 May 2018.

Zhang et al. Circulation. 2018 May 1;137(18):1934-1948. Link

The results of PEXIVAS have been released on May 25th, 2018

The very awaited results of the primary endpoints (mortality and ESRD at 1 year) of the PEXIVAS study have been presented by Michael Walsh at the ERA meeting: there is no difference in these outcomes between the arms with or without PLEX! There is no difference in term of efficacy between the standard and the lighter steroid regimen arm, but those in the latter showed less severe infections during year 1. Let's wait for the article now! CPx, 26 May 2018.

MAINRITSAN 1 long-term and MAINRITSAN 2 articles are published

The results of the 60-month follow-up of the MAINRITSAN (1) study have been published in ARD, and confirm that systematic reinfusions of rituximab (500mg at the time of remission, then 2 weeks later and again 6, 12 and 18 months later) achieved a lower rate of major relapses at 60 months than azathioprine (given until month 22). Major relapse-free survival rates were 71.9% versus 41.9% at 60  months, respectively (P=0.003). Rituximab is not yet approved for maintenance in Canada.

In parallel, the results of the MAINRITSAN 2 study were also published and showed that the rate of (major and minor) relapses at 28 months was 9.9% with the MAINRITSAN 1 regimen (500mg at the time of remission, then 2 weeks later and again 6, 12 and 18 months later) compared to 17.3%  (P=0.22) with a tailored-infusion regimen (500mg at remission, then up to every 3 months depending on the ANCA titer and the B cell count). Patients in the tailored-infusion arm received less infusions (median of 3), which would make it a cost-saving strategy, although it requires a close monitoring (every 3 months) and an efficient action plan (to give a rapid infusion when indicated). The difference observed in the relapse rate is not significant, but may be worrisome for some patients who are "forced" to chose the tailored-infusion regimen (and pay out of pocket for their rituximab infusions). Again, rtuximab is anyhow not yet approved for maintenance in Canada, using any of these two strategies. CPx, 06 May 2018.

Charles et al. Ann Rheum Dis. 2018 Apr 25. Link

Terrier et al. Ann Rheum Dis. 2018 May 3. Link

Health Canada now also approves tocilizumab for the treament of GCA

On October 27th, 2017, Health Canada has approved tocilizumab for the treatment of GCA, following the FDA approval. Let's now see who will be covered (the criteria) in each province precisely. CPx, 28 October 2017.

FDA approves tocilizumab for the treament of GCA

On May 22nd, 2017, the U.S. Food and Drug Administration expanded the approved use of subcutaneous Actemra (tocilizumab) to treat adults with giant cell arteritis, based on the positive outcome of the Phase III GiACTA study evaluating tocilizumab in patients with GCA (and a previous smaller study from Switzerland). Let's now what will happen in other countries, including in Canada, then at each provincial level regarding the criteria for coverage and reimbursement (i.e. the practical indications). CPx, 03 June 2017.

Link to FDA:

ARChiVe's pediatric cohort of GPA and MPA.

Congratulation to David Cabral (a CanVasc core member) and colleagues (including from Canada, UK, USA, Italy, Russia and India), who report the largest cohort of children with GPA (n=183) or MPA (n=48) published thus far. The ARChiVe initiative enrolled these patients into the online RedCap registry between March 2007 and November 2015 (and it is still running!). Previous largest cohort from another group (PRINTO) reported on 56 patients.

Main findings of this first descriptive analysis (there will likely be other papers soon, including on follow-up and outcomes) shows that, using the EMA algorithm (which often led to the re-classification of the diagnoses of MPA to GPA made by the treating physicians, or, but less often, from GPA to MPA), children with MPA are younger at diagnosis than those with GPA (13.4 versus 11.2 years), have less frequent lung involvement (44% versus 74%), with less alveolar hemorrhage (15% versus 42%) but more often renal failure requiring dialysis at disease onset (25% versus 13%). Subglottic stenosis occurred in 10% of GPA patients (none in MPA, based on the EMA algorithm), and nasal collapse in 8%. Von Willebrand antigen was elevated in >60% of patients, in both groups (this dosage is not routine in adults). Most children (76%) received cyclophosphamide-based induction, 10-13% received rituximab-based induction (for new diagnosis), and 21% had plasma exchange therapy. Female represented 64% of the patients, 55% were white and mean diagnosis delay was 1.6 months for MPA and  2.1 months for GPA (shorter than in adults by almost 4 months).  CPx, 10 Oct 2016.

Cabral DA et al. Comparing Presenting Clinical Features in 48 Children With Microscopic Polyangiitis to 183 Children Who Have Granulomatosis With Polyangiitis (Wegener's): An ARChiVe Cohort Study. Arthritis Rheumatol. 2016;68(10):2514-26.  Link 

EUVAS-EULAR recommendations for ANCA-associated vasculitides.

A few months after the publication (in November) of the first Canadian recommendations for the management of ANCA-associated vasculitides (link), the equivalent European EUVAS-EULAR updated recommendations are now out (they had to be named EULAR/ERA-EDTA for some internal reasons, out of the topic of this post, but all of us will likely refer to them as the "updated EUVAS guidelines").

Whereas most points are pretty similar, which is reassuring, there are a couple of subtle differences. The CanVasc recommendations included more points and covered more aspects of the diseases, including discussion on pregnancy and pediatric issues, whereas the EUVAS-EULAR ones do not. On the other hand, the EULAR-EUVAS recommendations mention MMF as an alternative to MTX for the treatment of limited GPA, which CanVasc did not at all (this was considered and discussed but at that time, available data were lacking to support MMF as an equivalent to MTX -- available data remains of limited convincing value, as somehow underscored between the lines in the EULAR-EUVAS explanatory text). Whereas CanVasc mentioned rituximab as an "alternative to AZA for maintenance, especially for patients with PR3-ANCA GPA", EULAR-EUVAS goes a little bit farther and lists directly AZA, MTX and rituximab (and MMF) as maintenance treatments, at the exact same levels, for patients with ANCA-associated vasculitides. This latter point sounds great to our Canadian ears and may help supporting applications for rituximab for maintenance (and hopefully its coverage for maintenance, earlier than [too] late) in Canada! The results of the ongoing RITAZAREM study should not be available before late 2018... it is a long time to wait (unless this study does not confirm the superiority of rituximab over AZA found in several retrospective studies and in the French RCT MAINRITSAN study...). - CPx, 15 July 2016.

Yates M, et al. EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis. Ann Rheum Dis. 2016 Jun 23. doi: 10.1136/annrheumdis-2016-209133. [Epub ahead of print]. Link