A brief discussion with Dr. Grainger and Dr. Hausmann covering autoinflammatory diseases for the adult rheumatologist and gout in New Zealand.
A brief chat with Dr. Robinson covering ACR Review Review course topics including:
- Interstitial lung disease
Juvenile Idiopathic Arthrits
Young children, and ANA are risks for uveitis for children in JIA, screen 3/12 in any children with pos ANA. Nigrovic #ACR13— Philip Robinson (@philipcrobinson) October 26, 2013
The only acceptable outcome in the growing skeleton is remission (JIA) #ACR13 Nigrovic— Dr. Ronan Kavanagh (@RonanTKavanagh) October 26, 2013
‘CREST’ diagnosis now Limited Cutaneous SSc. Centromere, Th/To Ab. GI, Lung (PAH, ILD), Digital Ulceres #acr13 Silver— Dr. Ronan Kavanagh (@RonanTKavanagh) October 26, 2013
Do not forget that patients with limited cutaneous SSc may develop PAH &ILD #ACR13— Jose Campos (@JoseCamposMD) October 26, 2013
Greater than 15mg of prednisone risks scleroderma renal crisis Silver #ACR13— Philip Robinson (@philipcrobinson) October 26, 2013
Rheumatic Disease and Pregnancy
Active SLE in pregnancy: 2x risk of preterm loss/preterm birth (3+ wks early). Try to have inactive 6 lupus 6mo before conception. #ACR13— Paul Sufka (@psufka) October 26, 2013
HCQ may reduce risk of neonatal heart block in Lupus pregnancy #acr13 Clowse— Dr. Ronan Kavanagh (@RonanTKavanagh) October 26, 2013
Prevent pre term birth and preecamplisa maternal hypertension and low birth wt with ‘baby’ aspirin 81mg day #acr13 Clowse— Dr. Ronan Kavanagh (@RonanTKavanagh) October 26, 2013
TNF inhibitors have minimal transfer to breastmilk (not sure about colostrum) #ACR13— Paul Sufka (@psufka) October 26, 2013
Obesity major risk factor for Ps arthritis, Obese PsA arthritis pts respond less well to anti TNF (Obesity ‘proinflammatory’). #acr13— Dr. Ronan Kavanagh (@RonanTKavanagh) October 26, 2013
We have a very effective treatment for OA, 38% patients obtaining little /no pain status: diet+exercise. But we want a magic drug... #ACR13— Jose Campos (@JoseCamposMD) October 26, 2013
Erosive OA w/ palpable inflammation may respond to adalimumab. Limited data though. We often try HCQ, but ineffective. #ACR13— Paul Sufka (@psufka) October 26, 2013
Opioid prescribing increased 400%in last 10 years. Wallace #acr13— Dr. Ronan Kavanagh (@RonanTKavanagh) October 26, 2013
“Although the US is the number 1 consumer of opioids in the world, there is no evidence that pain outcomes are better” #ACR13— Paul Sufka (@psufka) October 26, 2013
Morbidity from DMARDs
Rituximab more appropriate than anti TNF for RA if malignancy in last 5 years #acr13 Bingham III— Dr. Ronan Kavanagh (@RonanTKavanagh) October 26, 2013
Ok to give zoster vaccine: prednisone <20mg/day or short course <2wk, methotrexate (at our typical doses), azathioprine/6MP #ACR13— Paul Sufka (@psufka) October 26, 2013
Rigby WF, et al. Safety of Rituximab in Combination with Other Biologic Disease-modifying Antirheumatic Drugs in Rheumatoid Arthritis: An Open-label Study. J Rheumatol. 2013 Apr 1. [Epub ahead of print]
As rheumatologists, we have become fairly comfortable with the safety profile of rituximab and other biologics when used as monotherapy, but probably have never used biologics in combination, fearing infectious complications.
about 20%–40% of patients do not achieve an adequate clinical response to biologic DMARD [monotherapy] treatment
Despite these inadequate responses, data to help choose the optimal biologic therapy are limited given the limited number of RCTs comparing biologic DMARDs.
This was an open label study of 176 patients looking at the combination of rituximab plus one other biologic (adalimumab, etanercept, abatacept, or infliximab). 58/178 (33%) patients were also on MTX.
The rate of serious infections were of highest concern in this study, but results were rather reassuring:
Four serious infections were reported over 48 weeks (2.7 events/100 patient-yrs, 95% CI 1.0–7.2).
Over the 48-week study period, 104 (59.1%) of patients, did experience some type of infection.
Although there was no control group in this study, the authors noted that these findings were similar to previous data:
it is striking that no evidence of an increased safety signal was observed
Also pointing out that:
This safety profile should be considered in the context of this treatment-refractory patient population
While combinations of biologic medications are a potential next step to study, I would expect this data to only very slowly emerge. Before the practice of using rituximab with other biologics becomes more mainsteam, much better data is certainly needed.
With the above study in mind, another paper that provides some useful data on which patients might be at higher risk of infections while receiving rituximab:
Gottenberg JE, et al. Risk factors for severe infections in patients with rheumatoid arthritis treated with rituximab in the autoimmunity and rituximab registry Arthritis Rheum. 2010 Sep;62(9):2625-32. doi: 10.1002/art.27555.
Which points out risk factors for infection such as:
low IgG level (<6 gm/liter) before initiation of RTX treatment (odds ratio 4.9 [95% confidence interval 1.6–15.2], P = 0.005)
chronic lung disease and/or cardiac insufficiency (OR 3.0 [95% CI 1.3–7.3], P = 0.01)
RA-related extraarticular involvement (OR 2.9 [95% CI 1.3–6.7], P = 0.009)
The authors suggest checking IgG levels prior to subsequent cycles of rituximab.
The Ig concentrations should also be assessed before each new cycle of RTX, given the cumulative risk of decreased Ig levels with repeated treatments with RTX
Smolen JS, et al. Maintenance, reduction, or withdrawal of etanercept after treatment with etanercept and methotrexate in patients with moderate rheumatoid arthritis (PRESERVE): a randomised controlled trial Lancet. 2013 Mar 16;381(9870):918-29. doi: 10.1016/S0140-6736(12)61811-X. Epub 2013 Jan 17.
Many patients will ask how long they need to continue taking certain medications. The PRESERVE trial is the first RCT looking at reduction or withdrawl of TNF inhibitors in RA.
This study is 52-week extension of an initial 36-week open-label trial of methotrexate plus etanercept 50mg weekly, and included only those patients who achieved sustained low disease activity.
participants were eligible for randomisation when they had completed the open-label stage (36 weeks) and achieved sustained low disease activity (mean DAS28 ≤3·2 from weeks 12 to 36 and DAS28 ≤3·2 at week 36).
604 patients were randomized 1:1:1: to:
- 50 mg etanercept plus methotrexate
- 25 mg etanercept plus methotrexate
- Placebo injection plus methotrexate
The primary endpoint was the proportion of patients with low disease activity at week 88
Percentage of patients acheiving primary endpoint:
- 50 mg etanercept + MTX: 82·6%
- 25 mg etanercept + MTX: 79·1%
- Placebo + MTX: 42·6%
No differences were noted in adverse events, specifically infections.
After acheiving remission, it appears that reducing the dose of etanercept to 25mg weekly is a viable option, and as the authors point out, potentially an economical option as well.