1 Demographic Data
Up to November 2018, a total of 4848 courses of biologics were used in 2935 patients (1692 women and 1243 men) with various rheumatic diseases, according to our Registry. The mean age at commencement of treatment was 47 (range 1-89). More than half of the patients suffered from rheumatoid arthritis while the others were mainly patients with ankylosing spondylitis and psoriatic arthritis. Other indications of the biologics are shown in Table 1. The longest duration of therapy was 174 months.
Indications of the biological agents
|No. of courses (%)|
|Rheumatoid arthritis||2553 (52.7)|
|Ankylosing spondylitis / Spondyloarthropathy||1424 (29.4)|
|Psoriatic arthritis||604 (12.5)|
|Juvenile idiopathic arthritis||40 (0.8)|
|Adult-onset Still’s disease||15 (0.3)|
|Behcet’s disease||13 (0.3)|
|Crohn’s disease||22 (0.5)|
|IgG4 Disease||2 (0.04)|
|Inflammatory myopathies||12 (0.3)|
|Myositis Ossificans||1 (0.02)|
|Sjogren’s syndrome||1 (0.02)|
|Systemic lupus erythematosus||36 (0.7)|
|Systemic vasculitides||7 (0.1)|
|MCTD/ Overlap Syndrome||112 (2.3)|
2 Co-morbid Conditions
The most common co-existing medical conditions of patients using biological agents were hypertension (19%), diabetes mellitus (7.1%), fatty liver (4.7%), depression (4.7%), peptic ulcer (4.4%), previous pulmonary tuberculosis (4.1%) and chronic hepatitis B infection (3.8%). Other co-morbid conditions reported were asthma (2.5%), ischemic heart disease (2.4%), liver disease (2.3%), renal disease (2.3%), cancer (2%), hyperthyroidism (1.8%), stroke (1%), heart attack (0.7%), congestive heart failure (0.6%), epilepsy (0.6%), previous extra-pulmonary tuberculosis (0.4%), COAD (0.4%), chronic hepatitis C infection (0.3%) and demyelination (0.03%).
3 Discontinuation of Treatment
The usage of biological agents is updated in Table 2 & Figures 1, 2, 3. About one-fourth of the treatment courses involved Etanercept, which remained the commonest biological agent ever used. Etanercept was also the most frequent agent that was currently used by patients (24.7%).
Biological / targeted DMARDs used
|No. of courses (%)||No. of patients (%)|
|(ever use)||(current use: up to Nov 2018)|
|Etanercept||1246 (25.7)||520 (24.7)|
|Adalimumab||814 (16.8)||403 (19.1)|
|Infliximab||766 (15.8)||93 (4.4)|
|Golimumab||686 (14.2)||363 (17.2)|
|Tocilizumab||542 (11.2)||303 (14.4)|
|Rituximab||208 (4.3)||91 (4.3)|
|Abatacept||206 (4.3)||77 (3.7)|
|Certolizumab||143 (3.0)||96 (4.6)|
|Tofacitinib||121 (3.0)||82 (3.9)|
|Secukinumab||71 (1.5)||63 (3.0)|
|Belimumab||17 (0.4)||8 (0.4)|
|Ustekinumab||16 (0.3)||6 (0.3)|
|Pamidronate||11 (0.2)||0 (0.0)|
|Remsima||1 (0.02)||1 (0.05)|
|(biosimilar of Infliximab)|
|Total||4848 (100)||2106 (100)|
The number of patients who withdrew from treatment at different time points is shown in Table 3. The three most commonly reported reasons for termination of treatment are lack of efficacy (46%), serious adverse effects (21%) and cost (11%). Other reasons for stopping treatment included marked improvement of disease activity (8%), end of research study (7%), patients’ preference (3%) etc.
Withdrawal of biological therapies
|Follow up duration reported to registry since commencement of biological therapy (months)|
|No. of courses registered in FU||4848||4416||3704||2905||2169||1782||1469||1230||1011||853||693||571||456||360||275||214||167||130||91||76||62||45||35||29||24||17||14||10||8||5||3|
|No. of courses continue||4848||3868||3148||2339||1899||1607||1336||1141||926||790||640||525||417||331||252||201||153||116||88||70||58||43||33||28||21||15||12||10||8||5||2|
|No. of withdrawal||0||548||556||566||270||175||133||89||85||63||53||46||39||29||23||13||14||14||3||6||4||2||2||1||3||2||2||0||0||0||1|
|Reasons for withdrawal|
|Lack of efficacy||0||187||297||286||124||68||60||34||41||35||26||19||20||14||15||6||4||7||2||4||2||1||1||0||1||1||1||0||0||0||1|
|End of sample||0||29||72||50||6||9||1||0||0||0||0||5||6||0||1||0||0||0||0||0||0||0||0||0||0||0||0||0||0||0||0|
|Plan for surgery / pregnancy||0||2||1||12||8||2||1||4||2||1||0||2||1||1||0||0||1||0||0||0||0||0||0||1||0||0||0||0||0||0||0|
4 Major Adverse Events Reported
There were 51 cases of malignant and pre-malignant conditions reported: lung cancer (N=5), rectum cancer (N=5), colon cancer (N=4), breast cancer (N=4), ovarian cancer (N=4), lymphoma (N=2), nasopharyngeal cancer (N=2), pulmonary MALT lymphoma (N=1), tongue cancer (N=1), caecum cancer (N=1), intraductal papillary mucinous neoplasm of pancreas (N=1), prostate cancer (N=1), stomach cancer (N=1), penile cancer (N=1), gall bladder cancer (N=1), cancer of urinary bladder (N=1), cancer of small intestine (N=1), kidney cancer (N=1), cancer of ampulla of vater (N=1), thyroid cancer (N=1), mandible cancer (N=1), adenocarcinoma (N=1), myeloma (N=1), cervical intra-epithelial neoplasia (CIN) (N=1), myelodysplastic syndrome (N=1), brain tumor (N=1), malignant melanoma (N=1), renal cell carcinoma (N=1), cervical cancer (N=1), cancer of nasal cavity (N=1), laryngeal cancer (N=1) and myeloproliferative neoplasms (N=1).
4.2 Infection Requiring Hospitalization
There were 172 episodes of infective complications requiring hospitalization. Over 55% of them (i.e. 95 cases) occurred during the first 12 months of biological therapy.
A total of 67 cases of TB were reported: 32 related to Infliximab, 12 related to Etanercept, 12 related to Adalimumab, 6 related to Golimumab, 3 related to Tocilizumab and 2 related to Tofacitinib. Half of the cases (i.e. 34 cases) occurred in the first year of treatment. Isoniazid chemoprophylaxis was given to 997 patients (22.3% of all courses of b/tsDMARDs) with latent TB as defined by either positive MT2 (≥10mm induration) or a positive IGRA test.